1 项目概述

2 项目流程

2.1 实验流程

Fig 2-1-1 10x单细胞实验流程图

1. 细胞质检
   取少量单细胞悬液，加入等体积0.4%台盼蓝染液，用 Countess® II Automated Cell Counter 对细胞计数，将活细胞浓度调整到理想浓度（1000~2000个/μL）。
2. 10X 标记 cDNA 片段
   含有 barcode 信息的凝胶珠与细胞和酶的混合物结合，进入储液器中被油分隔开，形成GEMs（Gel Beads-In-Emulsions）。之后，凝胶珠溶解释放含有Barcode序列的捕获序列，逆转录 cDNA 片段，并对样本进行标记。将凝胶珠破碎并打碎油滴，以 cDNA 为模板进行 PCR 扩增。将所有GEMs的产物混合，构建标准测序文库。
3. 标准测序文库建库
   首先将 cDNA 酶切打断成 200~300bp 左右的片段，然后经过末端修复、加A尾、测序接头 P5 、P7和sample index等常规二代测序文库构建步骤，最后进行 PCR 扩增得到 DNA 文库。
4. 文库测序
   利用Illumina测序平台的PE150测序模式对建好的文库进行高通量测序。

2.2 分析流程

Fig 2-2-1 10x单细胞分析流程图

广州基迪奥生物科技有限公司

3 测序数据质控和表达量定量

3.1 测序数据基本质控

使用cellranger^[1]，我们可以对测序质量进行质控，去除测序质量低的reads，并对每个样本测的reads数和测序质量进行初步统计。

Tab 3-1-1 各样本测序数据统计表

Sample	Number of Reads	Valid Barcodes	Sequencing Saturation	Q30 Bases in Barcode	Q30 Bases in RNA Read	Q30 Bases in UMI
AdjacNormal	304,261,171	97.9%	55.0%	96.1%	91.6%	94.9%
FBBST	291,896,693	97.7%	53.9%	96.3%	92.1%	95.2%

3.2 数据定量

使用cellranger，我们将reads与参考基因组进行比对，将reads注释为特定基因；再对UMI进行修正和统计后，获得未过滤的feature-barcode矩阵；根据未过滤的feature-barcode矩阵，cellranger对数据中的细胞和非细胞进行识别和区分，并绘制为rank-plot图，直观体现有效细胞鉴定结果。

Tab 3-2-1 各样本比对结果统计表

Sample	Estimated Number of Cells	Fraction Reads in Cells	Mean Reads per Cell	Median Genes per Cell	Total Genes Detected	Median UMI Counts per Cell	Reads Mapped Confidently to Genome	Reads Mapped Confidently to Intergenic Regions	Reads Mapped Confidently to Intronic Regions	Reads Mapped Confidently to Exonic Regions	Reads Mapped Confidently to Transcriptome
AdjacNormal	8,967	91.2%	33,931	1,699	27,158	3,891	94.3%	4.0%	12.5%	77.8%	72.4%
FBBST	11,788	92.6%	24,762	1,665	26,827	3,536	94.1%	4.1%	19.4%	70.6%	64.8%

各样本质控、定量结果报告：

• AdjacNormal : 1.Expression/CellRanger_Report/CellRanger.AdjacNormal.result.html
• FBBST : 1.Expression/CellRanger_Report/CellRanger.FBBST.result.html

3.3 最终鉴定细胞表达量矩阵

基于UMI修正和有效细胞鉴定后的结果，我们可以使用UMI条数对基因进行定量，获得如下的细胞-基因表达量定量结果。

Tab 3-3-1 样本AdjacNormal所有细胞各个基因UMI丰度信息表（示例，前10个细胞，前20个基因）

GeneID	Name	AAACCCAAGAAGATCT-1	AAACCCAAGACTCGAG-1	AAACCCACACTGGATT-1	AAACCCACAGAGGCTA-1	AAACCCAGTTTGTTCT-1	AAACCCATCGGAAGGT-1	AAACCCATCTAGCCAA-1	AAACGAAAGAGGATCC-1	AAACGAAAGCACTCCG-1
ENSG00000284662	OR4F16	0	0	0	0	0	0	0	0	0
ENSG00000186827	TNFRSF4	0	0	0	0	0	0	0	0	0
ENSG00000186891	TNFRSF18	0	0	2	0	0	0	0	0	0
ENSG00000160072	ATAD3B	0	0	0	0	0	0	0	0	0
ENSG00000041988	THAP3	1	1	0	0	0	0	0	0	0
ENSG00000260179	ENSG00000260179	0	0	0	0	0	0	0	0	0
ENSG00000234396	ENSG00000234396	0	0	0	0	0	0	0	0	0
ENSG00000228037	ENSG00000228037	0	0	0	0	0	0	0	0	0
ENSG00000142611	PRDM16	0	0	0	0	0	0	0	0	0
ENSG00000067606	PRKCZ	0	0	0	0	0	0	0	0	0
ENSG00000131584	ACAP3	0	0	0	0	0	1	1	0	0
ENSG00000227589	TP73-AS3	0	0	0	0	0	0	0	0	0
ENSG00000237402	CAMTA1-IT1	0	0	0	0	0	0	0	0	0
ENSG00000284616	ENSG00000284616	0	0	0	0	0	0	0	0	0
ENSG00000169972	PUSL1	0	0	0	0	0	0	0	0	0
ENSG00000157911	PEX10	0	0	0	0	0	1	0	0	0
ENSG00000224051	CPTP	0	0	0	0	0	0	0	0	0
ENSG00000228750	LINC01672	0	0	0	0	0	0	0	0	0
ENSG00000238260	ENSG00000238260	0	0	0	0	0	0	0	0	0
ENSG00000260972	ENSG00000260972	0	0	0	0	0	0	0	0	0

备注：由于单个细胞在某个瞬间，只有小部分基因表达，因此表中大量基因UMI丰度为0。

UMI定量总表文件：

• AdjacNormal : 1.Expression/expressions/AdjacNormal/expression.xls
• FBBST : 1.Expression/expressions/FBBST/expression.xls

广州基迪奥生物科技有限公司

4 单细胞亚群分类

在cellranger完成基因表达量鉴定后，我们将表达量矩阵转入Seurat^[2]进行后续的分析。

4.1 非正常细胞的进一步过滤

1. 单细胞中鉴定到的基因数量（200-7500）。对于同一种细胞来说，表达基因的数量一般维持在一定范围内，如果该值过高，可能是一个GEM中包裹了多种细胞类型，这样的barcode应该剔除
2. 单细胞中UMI的总数（小于40000）。单个细胞中可以存在的mRNA总量是有限的，如果UMI总数过高，则可能是两个或两个以上的细胞进入同一个GEM中，这样的细胞应该剔除
3. 单细胞中线粒体基因表达量比例（小于10%）。细胞凋亡通常伴随着线粒体基因的高表达，所以线粒体基因的高表达意味着细胞状态不佳，这些细胞在实验过程中受到了不良刺激，不利于后续分析反应真实的细胞情况，这样的细胞应该剔除

Tab 4-1-1 过滤前后各个样本中细胞数据量统计表

Samples	before_filter_num	after_filter_num	pct	before_filter_median_UMI_per_cell	after_filter_median_UMI_per_cell	before_filter_median_genes_per_cell	after_filter_median_genes_per_cell	before_filter_median_MT_per_cell	after_filter_median_MT_per_cell
AdjacNormal	8967	7584	84.58%	3891	3518	1699	1578	2.50762453405625	2.41970054396315
FBBST	11788	10473	88.84%	3536	3285	1665	1581	2.45075534927346	2.3971669844729

Fig 4-1-1 过滤前后各个样本细胞基本信息的分布图

4.2 单细胞亚群分类

在去除低质量细胞后，我们需要进行批次效应矫正。首先对所有样本进行典型相关分析（Canonical Correspondence Analysis, CCA），然后寻找细胞间的最近邻接关系（Mutual Nearest Neighbors, MNN），以此构建细胞间的对应关系，最后，多个样本以细胞间对应关系作为锚点（anchors）完成数据整合并完成批次效应矫正^[3]。

Tab 4-2-1 细胞亚群分类结果统计表

Cluster	Cells number	Median Genes per Cell	Median UMI Counts per Cell
0	2895	1379	2991
1	2681	1768	3646
2	1904	1125	2055
3	1880	3194.5	10481.5
4	1696	2582	8168
5	1555	1492	2853
6	1426	4260.5	13391.5
7	1248	1313.5	2612.5
8	774	2839.5	7368.5
9	516	488.5	611
10	339	4591	22753
11	337	1541	3173
12	245	628	919
13	230	1363.5	2707.5
14	152	1241	2808.5
15	127	2157	5201
16	33	1019	1815
17	19	1246	2474

Tab 4-2-2 各样本在各个亚群中细胞数量统计表

Cluster	AdjacNormal	FBBST
Total	7584 (100%)	10473 (100%)
0	1463 (19.29%)	1432 (13.67%)
1	504 (6.65%)	2177 (20.79%)
2	779 (10.27%)	1125 (10.74%)
3	1046 (13.79%)	834 (7.96%)
4	731 (9.64%)	965 (9.21%)
5	483 (6.37%)	1072 (10.24%)
6	1074 (14.16%)	352 (3.36%)
7	602 (7.94%)	646 (6.17%)
8	209 (2.76%)	565 (5.39%)
9	16 (0.21%)	500 (4.77%)
10	278 (3.67%)	61 (0.58%)
11	120 (1.58%)	217 (2.07%)
12	48 (0.63%)	197 (1.88%)
13	89 (1.17%)	141 (1.35%)
14	58 (0.76%)	94 (0.9%)
15	38 (0.5%)	89 (0.85%)
16	31 (0.41%)	2 (0.02%)
17	15 (0.2%)	4 (0.04%)

Fig 4-2-1 各样本中各亚群细胞数量堆叠图		Fig 4-2-2 各样本中各亚群细胞数量百分比堆叠图

Fig 4-2-3 各亚群中各个样本细胞数量堆叠图		Fig 4-2-4 各亚群中各个样本细胞数量百分比堆叠图

进一步，我们计算两个细胞亚群之间相关性并绘制成热图。图中具有高度相关性的两个细胞亚群具有比较相似的基因表达模式，可能是同一种细胞类型。这张相关性热图为人工细胞亚群鉴定提供了一定的指导作用。

Fig 4-2-5 各亚群相关性热图

基因在各个亚群中表达量的均值表：2.Cluster/2.cluster/AllGene.avg_exp.annot.xls

Tab 4-2-3 基因在各个亚群中表达量的均值表（前20行）

Gene_ID	Gene_name	Cluster 0	Cluster 1	Cluster 2	Cluster 3	Cluster 4	Cluster 5	Cluster 6	Cluster 7	Cluster 8	Cluster 9	Cluster 10	Cluster 11	Cluster 12	Cluster 13	Cluster 14	Cluster 15	Cluster 16	Cluster 17	Description	KEGG_A_class	KEGG_B_class	Pathway	K_ID	GO Component	GO Function	GO Process
ENSG00000284662	OR4F16	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	olfactory receptor family 4 subfamily F member 16 [Source:HGNC Symbol;Acc:HGNC:15079]	Organismal Systems	Sensory system	ko04740//Olfactory transduction	K04257	GO:0005886//plasma membrane;GO:0016020//membrane;GO:0016021//integral component of membrane	GO:0004930//G protein-coupled receptor activity;GO:0004984//olfactory receptor activity;GO:0005515//protein binding	GO:0007165//signal transduction;GO:0007186//G protein-coupled receptor signaling pathway;GO:0007608//sensory perception of smell;GO:0050896//response to stimulus;GO:0050911//detection of chemical stimulus involved in sensory perception of smell
ENSG00000186827	TNFRSF4	0.571319134310679	0.854804775926441	0.0886945608266107	0.0411813181324674	0.0459722410242971	0.132849759669874	0.0455793136410357	0.108024877614492	0.671205904238265	0.0950901834014234	0.0297926458980379	10.2961592216472	0.438504175278641	0.301413694727988	0.0163595380623829	1.11102751255792	0.12594775687045	0.535134098611364	TNF receptor superfamily member 4 [Source:HGNC Symbol;Acc:HGNC:11918]	Environmental Information Processing	Signaling molecules and interaction	ko04060//Cytokine-cytokine receptor interaction	K05142	GO:0005886//plasma membrane;GO:0005887//integral component of plasma membrane;GO:0009897//external side of plasma membrane;GO:0009986//cell surface;GO:0016020//membrane;GO:0016021//integral component of membrane	GO:0001618//virus receptor activity;GO:0005031//tumor necrosis factor-activated receptor activity;GO:0005515//protein binding	GO:0002639//positive regulation of immunoglobulin production;GO:0006954//inflammatory response;GO:0006955//immune response;GO:0016032//viral process;GO:0030890//positive regulation of B cell proliferation;GO:0033209//tumor necrosis factor-mediated signaling pathway;GO:0042098//T cell proliferation;GO:0043433//negative regulation of DNA-binding transcription factor activity;GO:0045892//negative regulation of transcription, DNA-templated;GO:0046718//viral entry into host cell
ENSG00000186891	TNFRSF18	0.492222631468637	0.550303413865535	0.03306341879192	0.0147676716619666	0.0280060012739941	0.28391943610913	0.0242797535541773	0.362012430573059	0.992146110680063	0.0538313339309717	0.0236655412770667	9.83778956783648	0.256282965918579	0.20111653019422	0.0396534778675174	3.01745921166969	0.2518955137409	0.60916179337232	TNF receptor superfamily member 18 [Source:HGNC Symbol;Acc:HGNC:11914]	Environmental Information Processing	Signaling molecules and interaction	ko04060//Cytokine-cytokine receptor interaction	K05154	GO:0005576//extracellular region;GO:0005886//plasma membrane;GO:0005887//integral component of plasma membrane;GO:0009897//external side of plasma membrane;GO:0016020//membrane;GO:0016021//integral component of membrane	GO:0005031//tumor necrosis factor-activated receptor activity;GO:0005515//protein binding	GO:0002687//positive regulation of leukocyte migration;GO:0006915//apoptotic process;GO:0007165//signal transduction;GO:0033209//tumor necrosis factor-mediated signaling pathway;GO:0042531//positive regulation of tyrosine phosphorylation of STAT protein;GO:0043066//negative regulation of apoptotic process;GO:0045589//regulation of regulatory T cell differentiation;GO:0045785//positive regulation of cell adhesion
ENSG00000160072	ATAD3B	0.138632779863634	0.159479920216027	0.166462062259581	0.107187129743599	0.17113712506947	0.176185621061974	0.122566349265399	0.161600439090728	0.27053528348597	0.114882697540063	0.203140050694117	0.153368637551429	0.206936916827169	0.086824826580096	0.0185584042677028	0.19102445510193	0.955257239476669	0	ATPase family AAA domain containing 3B [Source:HGNC Symbol;Acc:HGNC:24007]	-	-	-	-	GO:0005739//mitochondrion;GO:0005743//mitochondrial inner membrane;GO:0005886//plasma membrane;GO:0016020//membrane;GO:0030667//secretory granule membrane;GO:0101003//ficolin-1-rich granule membrane	GO:0000166//nucleotide binding;GO:0005524//ATP binding;GO:0008270//zinc ion binding;GO:0016887//ATPase activity	GO:0007005//mitochondrion organization;GO:0043312//neutrophil degranulation
ENSG00000041988	THAP3	0.222576090125024	0.254218181677149	0.324768520333713	0.158968570686077	0.140669796755002	0.28624911940028	0.229356457621054	0.239427360661356	0.201422273284317	0.174362682532812	0.202380890520516	0.24735812396858	0.26639974750773	0.229920831794215	0.168852948377452	0.0655681206736036	0.387473866858325	0.469087156393658	THAP domain containing 3 [Source:HGNC Symbol;Acc:HGNC:20855]	-	-	-	-	-	GO:0003677//DNA binding;GO:0005515//protein binding;GO:0046872//metal ion binding	GO:0045944//positive regulation of transcription by RNA polymerase II
ENSG00000260179	ENSG00000260179	0.00176416314275079	0.00216103795517402	0	0.00123513316333043	0	0	0	0	0	0	0.00206992667698732	0	0	0	0	0	0	0	novel transcript	-	-	-	-	-	-	-
ENSG00000234396	ENSG00000234396	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	novel transcript	-	-	-	-	-	-	-
ENSG00000228037	ENSG00000228037	0.0435162805262702	0.106923619194447	0.0286091165748503	0.00435174916806504	0.00147735931521523	0.0475932100688336	4.34891331528534e-04	0.0202925705186917	0.0612190801680294	0	0.00415047036807142	0.0292817915326334	0.0113662841912036	0.0311789071067968	0.0780190458014103	0.0248513693096251	0	0	novel transcript	-	-	-	-	-	-	-
ENSG00000142611	PRDM16	0	0.00630616044870909	0	0	0	0	0	0	9.10621415338799e-04	0	0	0	0	0	0	0	0	0	PR/SET domain 16 [Source:HGNC Symbol;Acc:HGNC:14000]	Organismal Systems	Environmental adaptation	ko04714//Thermogenesis	K22410	GO:0005634//nucleus;GO:0005654//nucleoplasm;GO:0005737//cytoplasm;GO:0005829//cytosol;GO:0016235//aggresome;GO:0017053//transcriptional repressor complex	GO:0000976//transcription regulatory region sequence-specific DNA binding;GO:0000978//RNA polymerase II proximal promoter sequence-specific DNA binding;GO:0001227//DNA-binding transcription repressor activity, RNA polymerase II-specific;GO:0001228//DNA-binding transcription activator activity, RNA polymerase II-specific;GO:0003677//DNA binding;GO:0003712//transcription coregulator activity;GO:0003713//transcription coactivator activity;GO:0005515//protein binding;GO:0008168//methyltransferase activity;GO:0016740//transferase activity;GO:0033613//activating transcription factor binding;GO:0043565//sequence-specific DNA binding;GO:0046872//metal ion binding;GO:0046974//histone methyltransferase activity (H3-K9 specific)	GO:0000122//negative regulation of transcription by RNA polymerase II;GO:0006357//regulation of transcription by RNA polymerase II;GO:0030154//cell differentiation;GO:0030512//negative regulation of transforming growth factor beta receptor signaling pathway;GO:0032259//methylation;GO:0043457//regulation of cellular respiration;GO:0045892//negative regulation of transcription, DNA-templated;GO:0045893//positive regulation of transcription, DNA-templated;GO:0045944//positive regulation of transcription by RNA polymerase II;GO:0050873//brown fat cell differentiation;GO:0051567//histone H3-K9 methylation;GO:0070828//heterochromatin organization;GO:0120162//positive regulation of cold-induced thermogenesis
ENSG00000067606	PRKCZ	0.164857617907362	0.111979317853525	0.176715763819762	0.00546885325610629	0.0164815990674967	0.211331782524252	0.0234821538755097	0.125339109164737	0.0816066274943033	0.0245769298487099	0.0175438949582023	0.134184428995894	0.040481101122585	0.0751409666815252	0.104519469835706	0.170212132774325	0.383201729093951	0	protein kinase C zeta [Source:HGNC Symbol;Acc:HGNC:9412]	Human Diseases;Cellular Processes;Environmental Information Processing;Organismal Systems;Organismal Systems;Cellular Processes;Environmental Information Processing;Organismal Systems;Human Diseases;Organismal Systems;Organismal Systems;Environmental Information Processing;Human Diseases;Human Diseases;Human Diseases	Infectious diseases;Transport and catabolism;Signal transduction;Immune system;Development;Cellular community - eukaryotes;Signal transduction;Endocrine system;Cardiovascular diseases;Endocrine system;Immune system;Signal transduction;Endocrine and metabolic diseases;Endocrine and metabolic diseases;Endocrine and metabolic diseases	ko05165//Human papillomavirus infection;ko04144//Endocytosis;ko04015//Rap1 signaling pathway;ko04062//Chemokine signaling pathway;ko04360//Axon guidance;ko04530//Tight junction;ko04390//Hippo signaling pathway;ko04910//Insulin signaling pathway;ko05418//Fluid shear stress and atherosclerosis;ko04926//Relaxin signaling pathway;ko04611//Platelet activation;ko04071//Sphingolipid signaling pathway;ko04931//Insulin resistance;ko04933//AGE-RAGE signaling pathway in diabetic complications;ko04930//Type II diabetes mellitus	K18952;K18952;K18952;K18952;K18952;K18952;K18952;K18952;K18952;K18952;K18952;K18952;K18952;K18952;K18952	GO:0001725//stress fiber;GO:0005634//nucleus;GO:0005635//nuclear envelope;GO:0005737//cytoplasm;GO:0005768//endosome;GO:0005815//microtubule organizing center;GO:0005829//cytosol;GO:0005886//plasma membrane;GO:0005911//cell-cell junction;GO:0005923//bicellular tight junction;GO:0005938//cell cortex;GO:0014069//postsynaptic density;GO:0016020//membrane;GO:0016324//apical plasma membrane;GO:0016363//nuclear matrix;GO:0030054//cell junction;GO:0031252//cell leading edge;GO:0031982//vesicle;GO:0035748//myelin sheath abaxonal region;GO:0043203//axon hillock;GO:0043231//intracellular membrane-bounded organelle;GO:0045121//membrane raft;GO:0045179//apical cortex;GO:0048471//perinuclear region of cytoplasm;GO:0070062//extracellular exosome;GO:0098685//Schaffer collateral - CA1 synapse;GO:0098978//glutamatergic synapse	GO:0000166//nucleotide binding;GO:0004672//protein kinase activity;GO:0004674//protein serine/threonine kinase activity;GO:0004697//protein kinase C activity;GO:0004698//calcium-dependent protein kinase C activity;GO:0005515//protein binding;GO:0005524//ATP binding;GO:0015459//potassium channel regulator activity;GO:0016301//kinase activity;GO:0016740//transferase activity;GO:0019901//protein kinase binding;GO:0043274//phospholipase binding;GO:0043560//insulin receptor substrate binding;GO:0044877//protein-containing complex binding;GO:0046872//metal ion binding;GO:0071889//14-3-3 protein binding	GO:0000226//microtubule cytoskeleton organization;GO:0001954//positive regulation of cell-matrix adhesion;GO:0006468//protein phosphorylation;GO:0006954//inflammatory response;GO:0007165//signal transduction;GO:0007166//cell surface receptor signaling pathway;GO:0007179//transforming growth factor beta receptor signaling pathway;GO:0007616//long-term memory;GO:0008284//positive regulation of cell proliferation;GO:0016310//phosphorylation;GO:0016477//cell migration;GO:0018105//peptidyl-serine phosphorylation;GO:0030010//establishment of cell polarity;GO:0031333//negative regulation of protein complex assembly;GO:0031584//activation of phospholipase D activity;GO:0032148//activation of protein kinase B activity;GO:0032733//positive regulation of interleukin-10 production;GO:0032736//positive regulation of interleukin-13 production;GO:0032753//positive regulation of interleukin-4 production;GO:0032754//positive regulation of interleukin-5 production;GO:0032869//cellular response to insulin stimulus;GO:0034613//cellular protein localization;GO:0035556//intracellular signal transduction;GO:0043066//negative regulation of apoptotic process;GO:0045630//positive regulation of T-helper 2 cell differentiation;GO:0046627//negative regulation of insulin receptor signaling pathway;GO:0046628//positive regulation of insulin receptor signaling pathway;GO:0047496//vesicle transport along microtubule;GO:0050732//negative regulation of peptidyl-tyrosine phosphorylation;GO:0050806//positive regulation of synaptic transmission;GO:0051092//positive regulation of NF-kappaB transcription factor activity;GO:0051222//positive regulation of protein transport;GO:0051346//negative regulation of hydrolase activity;GO:0051899//membrane depolarization;GO:0060081//membrane hyperpolarization;GO:0060291//long-term synaptic potentiation;GO:0070374//positive regulation of ERK1 and ERK2 cascade;GO:0070528//protein kinase C signaling;GO:0072659//protein localization to plasma membrane;GO:0098696//regulation of neurotransmitter receptor localization to postsynaptic specialization membrane;GO:1990138//neuron projection extension;GO:2000463//positive regulation of excitatory postsynaptic potential;GO:2000553//positive regulation of T-helper 2 cell cytokine production
ENSG00000131584	ACAP3	0.204985808996599	0.147587686315065	0.17820169915382	0.152262182838052	0.163719826594889	0.155240270078059	0.230011999091701	0.177554092448075	0.258459406206497	0.077901928734916	0.220774039898479	0.0905928989244729	0.174514748079355	0.113414150798349	0.0603531920718237	0.157648999797185	2.40848258259307	0.473316038698781	ArfGAP with coiled-coil, ankyrin repeat and PH domains 3 [Source:HGNC Symbol;Acc:HGNC:16754]	Cellular Processes	Transport and catabolism	ko04144//Endocytosis	K12489	GO:0030426//growth cone	GO:0005096//GTPase activator activity;GO:0005515//protein binding;GO:0046872//metal ion binding	GO:0001764//neuron migration;GO:0010975//regulation of neuron projection development;GO:0043547//positive regulation of GTPase activity
ENSG00000227589	TP73-AS3	0	0	0	0	2.43796833371691e-04	0	0	0	0	0	0	0	0	0	0	0	0	0	TP73 antisense RNA 3 [Source:HGNC Symbol;Acc:HGNC:40590]	-	-	-	-	-	-	-
ENSG00000237402	CAMTA1-IT1	0	0	0	0	0	0	0.00176436314390726	0	0	0	0	0	0	0	0	0	0	0	CAMTA1 intronic transcript 1 [Source:HGNC Symbol;Acc:HGNC:41446]	-	-	-	-	-	-	-
ENSG00000284616	ENSG00000284616	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	novel transcript	-	-	-	-	-	-	-
ENSG00000169972	PUSL1	0.198948760370528	0.139497895815801	0.150867365307774	0.147796435832076	0.180607107830079	0.136381821220226	0.206277223545461	0.152928158282908	0.174235532342295	0.22691171788774	0.2172043281867	0.143619362671773	0.00225978997511971	0.109993631012645	0.105743295097218	0.156872927367193	0.163888752314929	0.221141088014153	pseudouridine synthase like 1 [Source:HGNC Symbol;Acc:HGNC:26914]	-	-	-	-	GO:0005739//mitochondrion;GO:0043231//intracellular membrane-bounded organelle	GO:0003723//RNA binding;GO:0009982//pseudouridine synthase activity;GO:0016853//isomerase activity;GO:0106029//tRNA pseudouridine synthase activity	GO:0001522//pseudouridine synthesis;GO:0008033//tRNA processing;GO:0009451//RNA modification;GO:0031119//tRNA pseudouridine synthesis
ENSG00000157911	PEX10	0.0652378581875412	0.106027734569619	0.0763772203583847	0.121536964253869	0.160603381933382	0.0807692873770581	0.278814613057272	0.0838521487429216	0.103966285929209	0.152721956079015	0.144071486607312	0.0971129353874815	0.0930452729069837	0.0782856765831594	0.0852248812898494	0.147567683317852	0	0.259396643407434	peroxisomal biogenesis factor 10 [Source:HGNC Symbol;Acc:HGNC:8851]	Cellular Processes	Transport and catabolism	ko04146//Peroxisome	K13346	GO:0005777//peroxisome;GO:0005778//peroxisomal membrane;GO:0005779//integral component of peroxisomal membrane;GO:0016020//membrane;GO:0016021//integral component of membrane	GO:0005515//protein binding;GO:0008022//protein C-terminus binding;GO:0008270//zinc ion binding;GO:0046872//metal ion binding	GO:0007031//peroxisome organization;GO:0008104//protein localization;GO:0016558//protein import into peroxisome matrix;GO:0016567//protein ubiquitination
ENSG00000224051	CPTP	0.159071305555589	0.15510461317126	0.174170672022555	0.104212710352233	0.0845182236333196	0.154539488250718	0.20663154880759	0.155708004782322	0.20452301438337	0.208336049499919	0.185009045465686	0.127363451295458	0.338756341993876	0.148393511054177	0.0706862705812407	0.0915941376665672	0.129334316274137	0	ceramide-1-phosphate transfer protein [Source:HGNC Symbol;Acc:HGNC:28116]	-	-	-	-	GO:0005634//nucleus;GO:0005640//nuclear outer membrane;GO:0005737//cytoplasm;GO:0005768//endosome;GO:0005794//Golgi apparatus;GO:0005829//cytosol;GO:0005886//plasma membrane;GO:0010008//endosome membrane;GO:0016020//membrane	GO:0005543//phospholipid binding;GO:0008289//lipid binding;GO:0120013//intermembrane lipid transfer activity;GO:1902387//ceramide 1-phosphate binding;GO:1902388//ceramide 1-phosphate transporter activity	GO:0006687//glycosphingolipid metabolic process;GO:0006869//lipid transport;GO:0010507//negative regulation of autophagy;GO:0032691//negative regulation of interleukin-1 beta production;GO:0035627//ceramide transport;GO:0120009//intermembrane lipid transfer;GO:1900226//negative regulation of NLRP3 inflammasome complex assembly;GO:1902389//ceramide 1-phosphate transport
ENSG00000228750	LINC01672	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	long intergenic non-protein coding RNA 1672 [Source:HGNC Symbol;Acc:HGNC:52460]	-	-	-	-	-	-	-
ENSG00000238260	ENSG00000238260	0	0.00453110756323733	0.00624506639754594	3.72750451028046e-04	0	0.00568739512846716	0.00206648803739124	0	0	0	0	0	0	0	0.00174364511102835	0	0	0	novel transcript	-	-	-	-	-	-	-
ENSG00000260972	ENSG00000260972	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	novel transcript	-	-	-	-	-	-	-

细胞与亚群对照表：2.Cluster/2.cluster/Cells.cluster.list.xls

Tab 4-2-4 细胞与亚群对照表（前20行）

Cells	Cluster	Samples
AdjacNormal_AAACCCAAGAAGATCT	1	AdjacNormal
AdjacNormal_AAACCCAAGACTCGAG	5	AdjacNormal
AdjacNormal_AAACCCACACTGGATT	5	AdjacNormal
AdjacNormal_AAACCCACAGAGGCTA	2	AdjacNormal
AdjacNormal_AAACCCAGTTTGTTCT	14	AdjacNormal
AdjacNormal_AAACCCATCGGAAGGT	6	AdjacNormal
AdjacNormal_AAACGAAAGAGGATCC	3	AdjacNormal
AdjacNormal_AAACGAAAGCACTCCG	0	AdjacNormal
AdjacNormal_AAACGAACAGTAGATA	1	AdjacNormal
AdjacNormal_AAACGAAGTAATGCGG	4	AdjacNormal
AdjacNormal_AAACGAAGTATCCTTT	0	AdjacNormal
AdjacNormal_AAACGAAGTGGCCACT	4	AdjacNormal
AdjacNormal_AAACGAAGTTGGCTAT	0	AdjacNormal
AdjacNormal_AAACGAAGTTTAGTCG	5	AdjacNormal
AdjacNormal_AAACGAATCGCATAGT	0	AdjacNormal
AdjacNormal_AAACGCTAGAATCTAG	7	AdjacNormal
AdjacNormal_AAACGCTAGAGATCGC	6	AdjacNormal
AdjacNormal_AAACGCTAGATGCGAC	2	AdjacNormal
AdjacNormal_AAACGCTAGGAACATT	0	AdjacNormal
AdjacNormal_AAACGCTAGGTTACCT	5	AdjacNormal

4.3 分类结果可视化

Fig 4-3-1 单细胞亚群分类tSNE图

4.4 单细胞亚群鉴定

以上单细胞亚群分类是基于细胞表达特征的相似性进行聚类的，每个亚群不具有生物学意义。所以，细胞鉴定一直是很重要但又比较繁琐的步骤。这里，我们使用singleR^[5]对所有细胞进行自动化注释，为后续的人工细胞鉴定工作提供参考。

singleR是通过细胞与参考数据库中细胞类型的相似度来自动化鉴定细胞类型，对于相似度较高的细胞类型的注释准确性会降低。所以，singleR的注释结果只能作为辅助手段，最终的细胞亚群鉴定结果依然需要人工鉴定的确认。

Tab 4-4-1 各样本在各个细胞类型中细胞数量统计表

Cluster	AdjacNormal	FBBST
Total	7584 (100%)	10473 (100%)
B_cell	51 (0.67%)	80 (0.76%)
Chondrocytes	120 (1.58%)	31 (0.3%)
CMP	10 (0.13%)	3 (0.03%)
DC	23 (0.3%)	182 (1.74%)
Endothelial_cells	13 (0.17%)	5 (0.05%)
Fibroblasts	35 (0.46%)	44 (0.42%)
GMP	1 (0.01%)	2 (0.02%)
HSC_-G-CSF	0 (0%)	4 (0.04%)
iPS_cells	1 (0.01%)	0 (0%)
Macrophage	1600 (21.1%)	1123 (10.72%)
Monocyte	500 (6.59%)	1003 (9.58%)
MSC	82 (1.08%)	51 (0.49%)
Neurons	3 (0.04%)	29 (0.28%)
Neutrophils	1 (0.01%)	6 (0.06%)
NK_cell	164 (2.16%)	217 (2.07%)
Osteoblasts	3 (0.04%)	13 (0.12%)
Platelets	1 (0.01%)	1 (0.01%)
Pre-B_cell_CD34-	5 (0.07%)	29 (0.28%)
Pro-B_cell_CD34+	1 (0.01%)	1 (0.01%)
Smooth_muscle_cells	59 (0.78%)	56 (0.53%)
T_cells	4156 (54.8%)	7360 (70.28%)
Tissue_stem_cells	755 (9.96%)	233 (2.22%)

Fig 4-4-1 各样本中各细胞类型细胞数量堆叠图		Fig 4-4-2 各样本中各细胞类型细胞数量百分比堆叠图

Fig 4-4-3 各细胞类型中各个样本细胞数量堆叠图		Fig 4-4-4 各细胞类型中各个样本细胞数量百分比堆叠图

Fig 4-4-5 各细胞类型在tSNE图的分布

各细胞亚群中各个细胞类型数量统计表：4.CellAnnotation/Cell.annotation.stat.xls

Tab 4-4-2 各细胞亚群中各个细胞类型数量统计表

Cluster	Cell.annotation (Maximum proportion)	B_cell	CMP	Chondrocytes	DC	Endothelial_cells	Fibroblasts	GMP	HSC_-G-CSF	MSC	Macrophage	Monocyte	NK_cell	Neurons	Neutrophils	Osteoblasts	Platelets	Pre-B_cell_CD34-	Pro-B_cell_CD34+	Smooth_muscle_cells	T_cells	Tissue_stem_cells	iPS_cells
0	T_cells(99.79%)	0(0.00%)	0(0.00%)	0(0.00%)	0(0.00%)	0(0.00%)	0(0.00%)	0(0.00%)	0(0.00%)	0(0.00%)	0(0.00%)	0(0.00%)	6(0.21%)	0(0.00%)	0(0.00%)	0(0.00%)	0(0.00%)	0(0.00%)	0(0.00%)	0(0.00%)	2889(99.79%)	0(0.00%)	0(0.00%)
1	T_cells(99.81%)	0(0.00%)	0(0.00%)	0(0.00%)	0(0.00%)	0(0.00%)	0(0.00%)	0(0.00%)	0(0.00%)	0(0.00%)	0(0.00%)	0(0.00%)	5(0.19%)	0(0.00%)	0(0.00%)	0(0.00%)	0(0.00%)	0(0.00%)	0(0.00%)	0(0.00%)	2676(99.81%)	0(0.00%)	0(0.00%)
2	T_cells(98.63%)	0(0.00%)	0(0.00%)	0(0.00%)	0(0.00%)	0(0.00%)	0(0.00%)	0(0.00%)	0(0.00%)	0(0.00%)	1(0.05%)	1(0.05%)	23(1.21%)	0(0.00%)	0(0.00%)	0(0.00%)	0(0.00%)	1(0.05%)	0(0.00%)	0(0.00%)	1878(98.63%)	0(0.00%)	0(0.00%)
3	Macrophage(85.90%)	0(0.00%)	0(0.00%)	0(0.00%)	9(0.48%)	0(0.00%)	0(0.00%)	0(0.00%)	0(0.00%)	0(0.00%)	1615(85.90%)	256(13.62%)	0(0.00%)	0(0.00%)	0(0.00%)	0(0.00%)	0(0.00%)	0(0.00%)	0(0.00%)	0(0.00%)	0(0.00%)	0(0.00%)	0(0.00%)
4	Monocyte(64.98%)	0(0.00%)	0(0.00%)	0(0.00%)	30(1.77%)	0(0.00%)	0(0.00%)	0(0.00%)	0(0.00%)	0(0.00%)	554(32.67%)	1102(64.98%)	1(0.06%)	0(0.00%)	5(0.29%)	0(0.00%)	0(0.00%)	2(0.12%)	0(0.00%)	0(0.00%)	2(0.12%)	0(0.00%)	0(0.00%)
5	T_cells(99.36%)	0(0.00%)	0(0.00%)	0(0.00%)	0(0.00%)	0(0.00%)	0(0.00%)	0(0.00%)	0(0.00%)	0(0.00%)	0(0.00%)	0(0.00%)	10(0.64%)	0(0.00%)	0(0.00%)	0(0.00%)	0(0.00%)	0(0.00%)	0(0.00%)	0(0.00%)	1545(99.36%)	0(0.00%)	0(0.00%)
6	Tissue_stem_cells(65.92%)	0(0.00%)	0(0.00%)	145(10.17%)	0(0.00%)	6(0.42%)	66(4.63%)	0(0.00%)	0(0.00%)	111(7.78%)	5(0.35%)	2(0.14%)	5(0.35%)	3(0.21%)	0(0.00%)	6(0.42%)	2(0.14%)	0(0.00%)	0(0.00%)	103(7.22%)	31(2.17%)	940(65.92%)	1(0.07%)
7	T_cells(76.20%)	0(0.00%)	0(0.00%)	0(0.00%)	0(0.00%)	0(0.00%)	0(0.00%)	0(0.00%)	0(0.00%)	0(0.00%)	0(0.00%)	0(0.00%)	297(23.80%)	0(0.00%)	0(0.00%)	0(0.00%)	0(0.00%)	0(0.00%)	0(0.00%)	0(0.00%)	951(76.20%)	0(0.00%)	0(0.00%)
8	T_cells(98.32%)	1(0.13%)	0(0.00%)	0(0.00%)	1(0.13%)	0(0.00%)	1(0.13%)	3(0.39%)	0(0.00%)	0(0.00%)	1(0.13%)	0(0.00%)	5(0.65%)	0(0.00%)	0(0.00%)	0(0.00%)	0(0.00%)	1(0.13%)	0(0.00%)	0(0.00%)	761(98.32%)	0(0.00%)	0(0.00%)
9	DC(27.33%)	0(0.00%)	0(0.00%)	6(1.16%)	141(27.33%)	12(2.33%)	12(2.33%)	0(0.00%)	2(0.39%)	22(4.26%)	108(20.93%)	55(10.66%)	4(0.78%)	29(5.62%)	1(0.19%)	10(1.94%)	0(0.00%)	9(1.74%)	0(0.00%)	12(2.33%)	45(8.72%)	48(9.30%)	0(0.00%)
10	Macrophage(83.19%)	0(0.00%)	0(0.00%)	0(0.00%)	2(0.59%)	0(0.00%)	0(0.00%)	0(0.00%)	0(0.00%)	0(0.00%)	282(83.19%)	45(13.27%)	0(0.00%)	0(0.00%)	0(0.00%)	0(0.00%)	0(0.00%)	0(0.00%)	0(0.00%)	0(0.00%)	10(2.95%)	0(0.00%)	0(0.00%)
11	T_cells(99.70%)	0(0.00%)	0(0.00%)	0(0.00%)	0(0.00%)	0(0.00%)	0(0.00%)	0(0.00%)	0(0.00%)	0(0.00%)	0(0.00%)	0(0.00%)	1(0.30%)	0(0.00%)	0(0.00%)	0(0.00%)	0(0.00%)	0(0.00%)	0(0.00%)	0(0.00%)	336(99.70%)	0(0.00%)	0(0.00%)
12	Macrophage(50.61%)	0(0.00%)	0(0.00%)	0(0.00%)	18(7.35%)	0(0.00%)	0(0.00%)	0(0.00%)	2(0.82%)	0(0.00%)	124(50.61%)	35(14.29%)	10(4.08%)	0(0.00%)	0(0.00%)	0(0.00%)	0(0.00%)	15(6.12%)	0(0.00%)	0(0.00%)	41(16.73%)	0(0.00%)	0(0.00%)
13	T_cells(96.09%)	0(0.00%)	0(0.00%)	0(0.00%)	0(0.00%)	0(0.00%)	0(0.00%)	0(0.00%)	0(0.00%)	0(0.00%)	2(0.87%)	1(0.43%)	5(2.17%)	0(0.00%)	1(0.43%)	0(0.00%)	0(0.00%)	0(0.00%)	0(0.00%)	0(0.00%)	221(96.09%)	0(0.00%)	0(0.00%)
14	B_cell(85.53%)	130(85.53%)	0(0.00%)	0(0.00%)	2(1.32%)	0(0.00%)	0(0.00%)	0(0.00%)	0(0.00%)	0(0.00%)	0(0.00%)	3(1.97%)	1(0.66%)	0(0.00%)	0(0.00%)	0(0.00%)	0(0.00%)	6(3.95%)	2(1.32%)	0(0.00%)	8(5.26%)	0(0.00%)	0(0.00%)
15	T_cells(96.06%)	0(0.00%)	0(0.00%)	0(0.00%)	0(0.00%)	0(0.00%)	0(0.00%)	0(0.00%)	0(0.00%)	0(0.00%)	0(0.00%)	0(0.00%)	5(3.94%)	0(0.00%)	0(0.00%)	0(0.00%)	0(0.00%)	0(0.00%)	0(0.00%)	0(0.00%)	122(96.06%)	0(0.00%)	0(0.00%)
16	Macrophage(90.91%)	0(0.00%)	0(0.00%)	0(0.00%)	2(6.06%)	0(0.00%)	0(0.00%)	0(0.00%)	0(0.00%)	0(0.00%)	30(90.91%)	0(0.00%)	1(3.03%)	0(0.00%)	0(0.00%)	0(0.00%)	0(0.00%)	0(0.00%)	0(0.00%)	0(0.00%)	0(0.00%)	0(0.00%)	0(0.00%)
17	CMP(68.42%)	0(0.00%)	13(68.42%)	0(0.00%)	0(0.00%)	0(0.00%)	0(0.00%)	0(0.00%)	0(0.00%)	0(0.00%)	1(5.26%)	3(15.79%)	2(10.53%)	0(0.00%)	0(0.00%)	0(0.00%)	0(0.00%)	0(0.00%)	0(0.00%)	0(0.00%)	0(0.00%)	0(0.00%)	0(0.00%)

Fig 4-4-6 Seurat分群与singleR细胞鉴定对应circos图

通过singleR，我们可以鉴定细胞的细胞类型；通过Seurat，我们可以得到细胞的聚类信息。通过这两个软件，我们可以将一组细胞按照细胞类型和细胞分群两种方式进行聚类。然后，我们计算各个细胞亚群的细胞与各个细胞类型的细胞之间的相关性，并绘制成热图，作为singleR细胞鉴定结果准确性的一个佐证。

Fig 4-4-7 Seurat分群与singleR鉴定细胞类型相关性热图

广州基迪奥生物科技有限公司

5 亚群上调表达基因分析

5.1 上调表达基因分析

Tab 5-1-1 各亚群上调基因数量统计表

Cluster	0	1	2	3	4	5	6	7	8	9	10	11	12	13	14	15	16	17
Number of DE genes	347	711	402	1520	1191	581	2583	281	1636	634	2100	366	450	269	257	1201	373	225

Fig 5-1-1 各亚群上调基因数量统计柱状图

各亚群差异基因注释表: 3.MarkerGene/DeGene.list.xls

Tab 5-1-2 各亚群差异基因注释表（前20行）

Target_Cluster	Gene ID	Gene Name	Target_Cluster_mean	Other_Cluster_mean	Log2FC	Pvalue	Qvalue	Description	KEGG_A_class	KEGG_B_class	Pathway	K_ID	GO Component	GO Function	GO Process
0	ENSG00000102245	CD40LG	1.91300797925581	0.0600418068668188	4.99373168770342	0	0	CD40 ligand [Source:HGNC Symbol;Acc:HGNC:11935]	Environmental Information Processing;Human Diseases;Environmental Information Processing;Environmental Information Processing;Human Diseases;Human Diseases;Organismal Systems;Human Diseases;Human Diseases;Organismal Systems;Human Diseases;Human Diseases;Human Diseases	Signaling molecules and interaction;Immune diseases;Signal transduction;Signaling molecules and interaction;Cardiovascular diseases;Immune diseases;Immune system;Immune diseases;Infectious diseases;Immune system;Immune diseases;Immune diseases;Infectious diseases	ko04060//Cytokine-cytokine receptor interaction;ko05322//Systemic lupus erythematosus;ko04064//NF-kappa B signaling pathway;ko04514//Cell adhesion molecules (CAMs);ko05416//Viral myocarditis;ko05320//Autoimmune thyroid disease;ko04672//Intestinal immune network for IgA production;ko05340//Primary immunodeficiency;ko05145//Toxoplasmosis;ko04660//T cell receptor signaling pathway;ko05330//Allograft rejection;ko05310//Asthma;ko05144//Malaria	K03161;K03161;K03161;K03161;K03161;K03161;K03161;K03161;K03161;K03161;K03161;K03161;K03161	GO:0005576//extracellular region;GO:0005615//extracellular space;GO:0005886//plasma membrane;GO:0005887//integral component of plasma membrane;GO:0009897//external side of plasma membrane;GO:0009986//cell surface;GO:0016020//membrane;GO:0016021//integral component of membrane	GO:0005125//cytokine activity;GO:0005164//tumor necrosis factor receptor binding;GO:0005174//CD40 receptor binding;GO:0005178//integrin binding;GO:0005515//protein binding	GO:0002637//regulation of immunoglobulin production;GO:0006954//inflammatory response;GO:0006955//immune response;GO:0007159//leukocyte cell-cell adhesion;GO:0007165//signal transduction;GO:0007229//integrin-mediated signaling pathway;GO:0007257//activation of JUN kinase activity;GO:0023035//CD40 signaling pathway;GO:0030168//platelet activation;GO:0030183//B cell differentiation;GO:0031295//T cell costimulation;GO:0032733//positive regulation of interleukin-10 production;GO:0032735//positive regulation of interleukin-12 production;GO:0032753//positive regulation of interleukin-4 production;GO:0033209//tumor necrosis factor-mediated signaling pathway;GO:0042100//B cell proliferation;GO:0042102//positive regulation of T cell proliferation;GO:0043066//negative regulation of apoptotic process;GO:0045190//isotype switching;GO:0050776//regulation of immune response;GO:0051092//positive regulation of NF-kappaB transcription factor activity;GO:2000353//positive regulation of endothelial cell apoptotic process
0	ENSG00000168685	IL7R	19.8526024749783	1.7146959246954	3.53330347834578	0	0	interleukin 7 receptor [Source:HGNC Symbol;Acc:HGNC:6024]	Human Diseases;Environmental Information Processing;Environmental Information Processing;Organismal Systems;Environmental Information Processing;Environmental Information Processing;Human Diseases	Cancers;Signal transduction;Signaling molecules and interaction;Immune system;Signal transduction;Signal transduction;Immune diseases	ko05200//Pathways in cancer;ko04151//PI3K-Akt signaling pathway;ko04060//Cytokine-cytokine receptor interaction;ko04640//Hematopoietic cell lineage;ko04630//Jak-STAT signaling pathway;ko04068//FoxO signaling pathway;ko05340//Primary immunodeficiency	K05072;K05072;K05072;K05072;K05072;K05072;K05072	GO:0005576//extracellular region;GO:0005654//nucleoplasm;GO:0005829//cytosol;GO:0005886//plasma membrane;GO:0009897//external side of plasma membrane;GO:0016020//membrane;GO:0016021//integral component of membrane;GO:0030669//clathrin-coated endocytic vesicle membrane	GO:0003823//antigen binding;GO:0004896//cytokine receptor activity;GO:0004917//interleukin-7 receptor activity;GO:0005515//protein binding	GO:0000018//regulation of DNA recombination;GO:0000902//cell morphogenesis;GO:0001915//negative regulation of T cell mediated cytotoxicity;GO:0006955//immune response;GO:0007165//signal transduction;GO:0007166//cell surface receptor signaling pathway;GO:0008284//positive regulation of cell proliferation;GO:0008361//regulation of cell size;GO:0010628//positive regulation of gene expression;GO:0030217//T cell differentiation;GO:0033089//positive regulation of T cell differentiation in thymus;GO:0038111//interleukin-7-mediated signaling pathway;GO:0042100//B cell proliferation;GO:0048535//lymph node development;GO:0048872//homeostasis of number of cells;GO:0050830//defense response to Gram-positive bacterium;GO:0061024//membrane organization;GO:0070233//negative regulation of T cell apoptotic process;GO:1904894//positive regulation of STAT cascade
0	ENSG00000165272	AQP3	2.37145484011634	0.211385728388676	3.4878225130521	0	0	aquaporin 3 (Gill blood group) [Source:HGNC Symbol;Acc:HGNC:636]	Organismal Systems	Excretory system	ko04962//Vasopressin-regulated water reabsorption	K09876	GO:0005654//nucleoplasm;GO:0005737//cytoplasm;GO:0005886//plasma membrane;GO:0005911//cell-cell junction;GO:0016020//membrane;GO:0016021//integral component of membrane;GO:0016323//basolateral plasma membrane	GO:0005515//protein binding;GO:0015204//urea transmembrane transporter activity;GO:0015250//water channel activity;GO:0015254//glycerol channel activity;GO:0015267//channel activity;GO:0042802//identical protein binding	GO:0002684//positive regulation of immune system process;GO:0003091//renal water homeostasis;GO:0006833//water transport;GO:0015793//glycerol transport;GO:0015840//urea transport;GO:0032526//response to retinoic acid;GO:0033280//response to vitamin D;GO:0042476//odontogenesis;GO:0045616//regulation of keratinocyte differentiation;GO:0051592//response to calcium ion;GO:0055085//transmembrane transport;GO:0070295//renal water absorption;GO:0071456//cellular response to hypoxia;GO:0071918//urea transmembrane transport;GO:0090650//cellular response to oxygen-glucose deprivation
0	ENSG00000111796	KLRB1	7.18293291032992	0.726748649149455	3.30504465074229	0	0	killer cell lectin like receptor B1 [Source:HGNC Symbol;Acc:HGNC:6373]	Human Diseases	Infectious diseases	ko05144//Malaria	K06543	GO:0005886//plasma membrane;GO:0016020//membrane;GO:0016021//integral component of membrane	GO:0004888//transmembrane signaling receptor activity;GO:0005515//protein binding;GO:0030246//carbohydrate binding	GO:0007166//cell surface receptor signaling pathway;GO:0050776//regulation of immune response
0	ENSG00000215788	TNFRSF25	2.03310266296568	0.303131607378251	2.74566687277985	0	0	TNF receptor superfamily member 25 [Source:HGNC Symbol;Acc:HGNC:11910]	Environmental Information Processing	Signaling molecules and interaction	ko04060//Cytokine-cytokine receptor interaction	K05160	GO:0005576//extracellular region;GO:0005829//cytosol;GO:0005886//plasma membrane;GO:0005887//integral component of plasma membrane;GO:0016020//membrane;GO:0016021//integral component of membrane	GO:0005031//tumor necrosis factor-activated receptor activity;GO:0005515//protein binding;GO:0038023//signaling receptor activity	GO:0006915//apoptotic process;GO:0007165//signal transduction;GO:0007166//cell surface receptor signaling pathway;GO:0033209//tumor necrosis factor-mediated signaling pathway;GO:0042981//regulation of apoptotic process;GO:0097190//apoptotic signaling pathway
0	ENSG00000069667	RORA	2.56941920829341	0.391332988691889	2.714973652211	0	0	RAR related orphan receptor A [Source:HGNC Symbol;Acc:HGNC:10258]	Organismal Systems;Human Diseases;Human Diseases;Organismal Systems	Immune system;Neurodegenerative disease;Immune diseases;Environmental adaptation	ko04659//Th17 cell differentiation;ko05017//Spinocerebellar ataxia;ko05321//Inflammatiory bowel disease (IBD);ko04710//Circadian rhythm	K08532;K08532;K08532;K08532	GO:0000785//chromatin;GO:0005634//nucleus;GO:0005654//nucleoplasm	GO:0000977//RNA polymerase II regulatory region sequence-specific DNA binding;GO:0000978//RNA polymerase II proximal promoter sequence-specific DNA binding;GO:0000981//DNA-binding transcription factor activity, RNA polymerase II-specific;GO:0001222//transcription corepressor binding;GO:0001223//transcription coactivator binding;GO:0003677//DNA binding;GO:0003700//DNA-binding transcription factor activity;GO:0004879//nuclear receptor activity;GO:0005515//protein binding;GO:0008013//beta-catenin binding;GO:0008134//transcription factor binding;GO:0008142//oxysterol binding;GO:0008270//zinc ion binding;GO:0043565//sequence-specific DNA binding;GO:0046872//metal ion binding;GO:0098531//transcription factor activity, direct ligand regulated sequence-specific DNA binding	GO:0001525//angiogenesis;GO:0006355//regulation of transcription, DNA-templated;GO:0006357//regulation of transcription by RNA polymerase II;GO:0006367//transcription initiation from RNA polymerase II promoter;GO:0006805//xenobiotic metabolic process;GO:0006809//nitric oxide biosynthetic process;GO:0007275//multicellular organism development;GO:0007623//circadian rhythm;GO:0008589//regulation of smoothened signaling pathway;GO:0010575//positive regulation of vascular endothelial growth factor production;GO:0010906//regulation of glucose metabolic process;GO:0019218//regulation of steroid metabolic process;GO:0019221//cytokine-mediated signaling pathway;GO:0021702//cerebellar Purkinje cell differentiation;GO:0021930//cerebellar granule cell precursor proliferation;GO:0030522//intracellular receptor signaling pathway;GO:0032922//circadian regulation of gene expression;GO:0036315//cellular response to sterol;GO:0042632//cholesterol homeostasis;GO:0042692//muscle cell differentiation;GO:0042752//regulation of circadian rhythm;GO:0042753//positive regulation of circadian rhythm;GO:0043030//regulation of macrophage activation;GO:0043124//negative regulation of I-kappaB kinase/NF-kappaB signaling;GO:0045599//negative regulation of fat cell differentiation;GO:0045893//positive regulation of transcription, DNA-templated;GO:0045944//positive regulation of transcription by RNA polymerase II;GO:0046068//cGMP metabolic process;GO:0048511//rhythmic process;GO:0050728//negative regulation of inflammatory response;GO:0070328//triglyceride homeostasis;GO:0071347//cellular response to interleukin-1;GO:0071356//cellular response to tumor necrosis factor;GO:0071456//cellular response to hypoxia;GO:0072539//T-helper 17 cell differentiation
0	ENSG00000117090	SLAMF1	1.54411484117213	0.265578321453917	2.53957076209276	0	0	signaling lymphocytic activation molecule family member 1 [Source:HGNC Symbol;Acc:HGNC:10903]	Human Diseases	Infectious diseases	ko05162//Measles	K06536	GO:0005576//extracellular region;GO:0005886//plasma membrane;GO:0009897//external side of plasma membrane;GO:0009986//cell surface;GO:0016020//membrane;GO:0016021//integral component of membrane;GO:0045335//phagocytic vesicle;GO:0070062//extracellular exosome	GO:0001618//virus receptor activity;GO:0003823//antigen binding;GO:0004888//transmembrane signaling receptor activity;GO:0005515//protein binding;GO:0038023//signaling receptor activity;GO:0042169//SH2 domain binding;GO:0042802//identical protein binding	GO:0001779//natural killer cell differentiation;GO:0001787//natural killer cell proliferation;GO:0002232//leukocyte chemotaxis involved in inflammatory response;GO:0002250//adaptive immune response;GO:0002277//myeloid dendritic cell activation involved in immune response;GO:0002376//immune system process;GO:0002725//negative regulation of T cell cytokine production;GO:0006909//phagocytosis;GO:0007155//cell adhesion;GO:0008284//positive regulation of cell proliferation;GO:0010759//positive regulation of macrophage chemotaxis;GO:0016032//viral process;GO:0031338//regulation of vesicle fusion;GO:0032689//negative regulation of interferon-gamma production;GO:0032695//negative regulation of interleukin-12 production;GO:0032715//negative regulation of interleukin-6 production;GO:0032720//negative regulation of tumor necrosis factor production;GO:0032729//positive regulation of interferon-gamma production;GO:0042104//positive regulation of activated T cell proliferation;GO:0045087//innate immune response;GO:0046330//positive regulation of JNK cascade;GO:0046649//lymphocyte activation;GO:0046718//viral entry into host cell;GO:0050790//regulation of catalytic activity;GO:0070374//positive regulation of ERK1 and ERK2 cascade;GO:2000349//negative regulation of CD40 signaling pathway;GO:2000510//positive regulation of dendritic cell chemotaxis;GO:2000556//positive regulation of T-helper 1 cell cytokine production
0	ENSG00000227507	LTB	9.97039880710432	2.6688962826689	1.9014079710329	0	0	lymphotoxin beta [Source:HGNC Symbol;Acc:HGNC:6711]	Environmental Information Processing;Environmental Information Processing;Human Diseases	Signaling molecules and interaction;Signal transduction;Immune diseases	ko04060//Cytokine-cytokine receptor interaction;ko04064//NF-kappa B signaling pathway;ko05323//Rheumatoid arthritis	K03157;K03157;K03157	GO:0005575//cellular_component;GO:0005615//extracellular space;GO:0005886//plasma membrane;GO:0016020//membrane;GO:0016021//integral component of membrane	GO:0005102//signaling receptor binding;GO:0005125//cytokine activity;GO:0005164//tumor necrosis factor receptor binding;GO:0005515//protein binding	GO:0006955//immune response;GO:0007165//signal transduction;GO:0007267//cell-cell signaling;GO:0010467//gene expression;GO:0032735//positive regulation of interleukin-12 production;GO:0033209//tumor necrosis factor-mediated signaling pathway;GO:0043588//skin development;GO:0048535//lymph node development
0	ENSG00000107742	SPOCK2	3.80441542197551	1.21612226314412	1.64538651167702	0	0	SPARC (osteonectin), cwcv and kazal like domains proteoglycan 2 [Source:HGNC Symbol;Acc:HGNC:13564]	-	-	-	-	GO:0005576//extracellular region;GO:0031012//extracellular matrix	GO:0005509//calcium ion binding;GO:0005515//protein binding;GO:0005539//glycosaminoglycan binding;GO:0008191//metalloendopeptidase inhibitor activity;GO:0050840//extracellular matrix binding	GO:0007416//synapse assembly;GO:0010811//positive regulation of cell-substrate adhesion;GO:0010951//negative regulation of endopeptidase activity;GO:0019800//peptide cross-linking via chondroitin 4-sulfate glycosaminoglycan;GO:0030198//extracellular matrix organization;GO:0045595//regulation of cell differentiation;GO:1990830//cellular response to leukemia inhibitory factor;GO:2000147//positive regulation of cell motility
0	ENSG00000115165	CYTIP	4.09208145434575	1.47914476377071	1.4680716069438	0	0	cytohesin 1 interacting protein [Source:HGNC Symbol;Acc:HGNC:9506]	-	-	-	-	GO:0005654//nucleoplasm;GO:0005737//cytoplasm;GO:0005768//endosome;GO:0005769//early endosome;GO:0005829//cytosol;GO:0005938//cell cortex	GO:0005515//protein binding	GO:0030155//regulation of cell adhesion
0	ENSG00000185201	IFITM2	5.70281711592152	2.23498258179171	1.35141117966027	0	0	interferon induced transmembrane protein 2 [Source:HGNC Symbol;Acc:HGNC:5413]	-	-	-	-	GO:0005765//lysosomal membrane;GO:0005886//plasma membrane;GO:0016020//membrane;GO:0016021//integral component of membrane;GO:0031902//late endosome membrane;GO:0032991//protein-containing complex	-	GO:0002376//immune system process;GO:0006955//immune response;GO:0009615//response to virus;GO:0034341//response to interferon-gamma;GO:0035455//response to interferon-alpha;GO:0035456//response to interferon-beta;GO:0035458//cellular response to interferon-beta;GO:0045071//negative regulation of viral genome replication;GO:0045087//innate immune response;GO:0046597//negative regulation of viral entry into host cell;GO:0051607//defense response to virus;GO:0060337//type I interferon signaling pathway
0	ENSG00000152518	ZFP36L2	11.1833600362829	4.40620151926007	1.34374632663532	0	0	ZFP36 ring finger protein like 2 [Source:HGNC Symbol;Acc:HGNC:1108]	Cellular Processes	Cell growth and death	ko04218//Cellular senescence	K18753	GO:0005634//nucleus;GO:0005737//cytoplasm	GO:0003723//RNA binding;GO:0005515//protein binding;GO:0035925//mRNA 3'-UTR AU-rich region binding;GO:0046872//metal ion binding	GO:0000165//MAPK cascade;GO:0000288//nuclear-transcribed mRNA catabolic process, deadenylation-dependent decay;GO:0006402//mRNA catabolic process;GO:0007275//multicellular organism development;GO:0009611//response to wounding;GO:0030097//hemopoiesis;GO:0033077//T cell differentiation in thymus;GO:0035019//somatic stem cell population maintenance;GO:0043488//regulation of mRNA stability;GO:0044344//cellular response to fibroblast growth factor stimulus;GO:0045577//regulation of B cell differentiation;GO:0045599//negative regulation of fat cell differentiation;GO:0048103//somatic stem cell division;GO:0060216//definitive hemopoiesis;GO:0061158//3'-UTR-mediated mRNA destabilization;GO:0070371//ERK1 and ERK2 cascade;GO:0071356//cellular response to tumor necrosis factor;GO:0071364//cellular response to epidermal growth factor stimulus;GO:0071385//cellular response to glucocorticoid stimulus;GO:0071560//cellular response to transforming growth factor beta stimulus;GO:0097011//cellular response to granulocyte macrophage colony-stimulating factor stimulus;GO:1900153//positive regulation of nuclear-transcribed mRNA catabolic process, deadenylation-dependent decay;GO:1901991//negative regulation of mitotic cell cycle phase transition;GO:2000737//negative regulation of stem cell differentiation
0	ENSG00000135046	ANXA1	8.55741443593119	3.64974206412139	1.22938045312089	0	0	annexin A1 [Source:HGNC Symbol;Acc:HGNC:533]	-	-	-	-	GO:0001533//cornified envelope;GO:0001891//phagocytic cup;GO:0005576//extracellular region;GO:0005615//extracellular space;GO:0005634//nucleus;GO:0005654//nucleoplasm;GO:0005737//cytoplasm;GO:0005768//endosome;GO:0005769//early endosome;GO:0005829//cytosol;GO:0005884//actin filament;GO:0005886//plasma membrane;GO:0005912//adherens junction;GO:0005925//focal adhesion;GO:0005929//cilium;GO:0009986//cell surface;GO:0010008//endosome membrane;GO:0016020//membrane;GO:0016323//basolateral plasma membrane;GO:0016324//apical plasma membrane;GO:0016328//lateral plasma membrane;GO:0019898//extrinsic component of membrane;GO:0030659//cytoplasmic vesicle membrane;GO:0031232//extrinsic component of external side of plasma membrane;GO:0031313//extrinsic component of endosome membrane;GO:0031410//cytoplasmic vesicle;GO:0031514//motile cilium;GO:0031901//early endosome membrane;GO:0031966//mitochondrial membrane;GO:0031982//vesicle;GO:0032991//protein-containing complex;GO:0042383//sarcolemma;GO:0042629//mast cell granule;GO:0042995//cell projection;GO:0062023//collagen-containing extracellular matrix;GO:0070062//extracellular exosome;GO:0097060//synaptic membrane	GO:0003697//single-stranded DNA binding;GO:0003727//single-stranded RNA binding;GO:0004859//phospholipase inhibitor activity;GO:0005102//signaling receptor binding;GO:0005509//calcium ion binding;GO:0005515//protein binding;GO:0005543//phospholipid binding;GO:0005544//calcium-dependent phospholipid binding;GO:0019834//phospholipase A2 inhibitor activity;GO:0036121//double-stranded DNA-dependent ATP-dependent DNA helicase activity;GO:0042802//identical protein binding;GO:0046872//metal ion binding;GO:0048306//calcium-dependent protein binding;GO:0098641//cadherin binding involved in cell-cell adhesion;GO:1990814//DNA/DNA annealing activity	GO:0001780//neutrophil homeostasis;GO:0002250//adaptive immune response;GO:0002376//immune system process;GO:0002548//monocyte chemotaxis;GO:0002685//regulation of leukocyte migration;GO:0006909//phagocytosis;GO:0006954//inflammatory response;GO:0007165//signal transduction;GO:0007166//cell surface receptor signaling pathway;GO:0007186//G protein-coupled receptor signaling pathway;GO:0007187//G protein-coupled receptor signaling pathway, coupled to cyclic nucleotide second messenger;GO:0008360//regulation of cell shape;GO:0009725//response to hormone;GO:0010165//response to X-ray;GO:0014070//response to organic cyclic compound;GO:0014839//myoblast migration involved in skeletal muscle regeneration;GO:0018149//peptide cross-linking;GO:0019221//cytokine-mediated signaling pathway;GO:0030073//insulin secretion;GO:0030216//keratinocyte differentiation;GO:0030850//prostate gland development;GO:0031018//endocrine pancreas development;GO:0031340//positive regulation of vesicle fusion;GO:0031394//positive regulation of prostaglandin biosynthetic process;GO:0031532//actin cytoskeleton reorganization;GO:0031960//response to corticosteroid;GO:0032355//response to estradiol;GO:0032508//DNA duplex unwinding;GO:0032652//regulation of interleukin-1 production;GO:0032717//negative regulation of interleukin-8 production;GO:0032743//positive regulation of interleukin-2 production;GO:0033031//positive regulation of neutrophil apoptotic process;GO:0035924//cellular response to vascular endothelial growth factor stimulus;GO:0042063//gliogenesis;GO:0042102//positive regulation of T cell proliferation;GO:0042127//regulation of cell proliferation;GO:0042493//response to drug;GO:0043065//positive regulation of apoptotic process;GO:0043066//negative regulation of apoptotic process;GO:0043086//negative regulation of catalytic activity;GO:0043434//response to peptide hormone;GO:0044849//estrous cycle;GO:0045087//innate immune response;GO:0045627//positive regulation of T-helper 1 cell differentiation;GO:0045629//negative regulation of T-helper 2 cell differentiation;GO:0045920//negative regulation of exocytosis;GO:0046632//alpha-beta T cell differentiation;GO:0046883//regulation of hormone secretion;GO:0050482//arachidonic acid secretion;GO:0050709//negative regulation of protein secretion;GO:0050727//regulation of inflammatory response;GO:0051384//response to glucocorticoid;GO:0070301//cellular response to hydrogen peroxide;GO:0070365//hepatocyte differentiation;GO:0070459//prolactin secretion;GO:0070555//response to interleukin-1;GO:0071385//cellular response to glucocorticoid stimulus;GO:0071621//granulocyte chemotaxis;GO:0090050//positive regulation of cell migration involved in sprouting angiogenesis;GO:0090303//positive regulation of wound healing;GO:0097350//neutrophil clearance;GO:0098609//cell-cell adhesion;GO:1900087//positive regulation of G1/S transition of mitotic cell cycle;GO:1900138//negative regulation of phospholipase A2 activity
0	ENSG00000133112	TPT1	76.0180732879778	36.2604121826145	1.0679471352051	0	0	tumor protein, translationally-controlled 1 [Source:HGNC Symbol;Acc:HGNC:12022]	-	-	-	-	GO:0000922//spindle pole;GO:0005615//extracellular space;GO:0005634//nucleus;GO:0005654//nucleoplasm;GO:0005737//cytoplasm;GO:0005771//multivesicular body;GO:0005829//cytosol;GO:0005881//cytoplasmic microtubule;GO:0070062//extracellular exosome	GO:0003723//RNA binding;GO:0005509//calcium ion binding;GO:0005515//protein binding;GO:0008134//transcription factor binding	GO:0006816//calcium ion transport;GO:0006874//cellular calcium ion homeostasis;GO:0009615//response to virus;GO:0019827//stem cell population maintenance;GO:0042981//regulation of apoptotic process;GO:0043066//negative regulation of apoptotic process;GO:1902230//negative regulation of intrinsic apoptotic signaling pathway in response to DNA damage;GO:2000384//negative regulation of ectoderm development
0	ENSG00000133639	BTG1	22.3320728397822	11.075226461292	1.0117809681624	0	0	BTG anti-proliferation factor 1 [Source:HGNC Symbol;Acc:HGNC:1130]	Genetic Information Processing	Folding, sorting and degradation	ko03018//RNA degradation	K14443	GO:0005634//nucleus;GO:0005654//nucleoplasm;GO:0005737//cytoplasm	GO:0003712//transcription coregulator activity;GO:0005515//protein binding;GO:0019899//enzyme binding;GO:0019900//kinase binding	GO:0006355//regulation of transcription, DNA-templated;GO:0006479//protein methylation;GO:0006979//response to oxidative stress;GO:0007283//spermatogenesis;GO:0008285//negative regulation of cell proliferation;GO:0016477//cell migration;GO:0030308//negative regulation of cell growth;GO:0043434//response to peptide hormone;GO:0045603//positive regulation of endothelial cell differentiation;GO:0045663//positive regulation of myoblast differentiation;GO:0045766//positive regulation of angiogenesis;GO:0045930//negative regulation of mitotic cell cycle;GO:2000271//positive regulation of fibroblast apoptotic process
0	ENSG00000109475	RPL34	34.1157057292684	17.2414861397072	0.984551926988731	0	0	ribosomal protein L34 [Source:HGNC Symbol;Acc:HGNC:10340]	Genetic Information Processing	Translation	ko03010//Ribosome	K02915	GO:0005737//cytoplasm;GO:0005783//endoplasmic reticulum;GO:0005829//cytosol;GO:0005840//ribosome;GO:0022625//cytosolic large ribosomal subunit;GO:0022626//cytosolic ribosome;GO:0070062//extracellular exosome	GO:0003723//RNA binding;GO:0003735//structural constituent of ribosome;GO:0005515//protein binding;GO:0045296//cadherin binding	GO:0000184//nuclear-transcribed mRNA catabolic process, nonsense-mediated decay;GO:0002181//cytoplasmic translation;GO:0006364//rRNA processing;GO:0006412//translation;GO:0006413//translational initiation;GO:0006614//SRP-dependent cotranslational protein targeting to membrane;GO:0019083//viral transcription
0	ENSG00000114942	EEF1B2	18.4608288963324	9.33304568384193	0.984047469348451	0	0	eukaryotic translation elongation factor 1 beta 2 [Source:HGNC Symbol;Acc:HGNC:3208]	-	-	-	-	GO:0005737//cytoplasm;GO:0005783//endoplasmic reticulum;GO:0005829//cytosol;GO:0005853//eukaryotic translation elongation factor 1 complex	GO:0003746//translation elongation factor activity;GO:0005085//guanyl-nucleotide exchange factor activity;GO:0005515//protein binding	GO:0006412//translation;GO:0006414//translational elongation;GO:0045471//response to ethanol;GO:0050790//regulation of catalytic activity
0	ENSG00000112306	RPS12	75.3066679327759	38.908434713506	0.952694670292979	0	0	ribosomal protein S12 [Source:HGNC Symbol;Acc:HGNC:10385]	Genetic Information Processing	Translation	ko03010//Ribosome	K02951	GO:0005654//nucleoplasm;GO:0005737//cytoplasm;GO:0005794//Golgi apparatus;GO:0005829//cytosol;GO:0005840//ribosome;GO:0016020//membrane;GO:0022626//cytosolic ribosome;GO:0022627//cytosolic small ribosomal subunit;GO:0043231//intracellular membrane-bounded organelle	GO:0003723//RNA binding;GO:0003735//structural constituent of ribosome;GO:0005515//protein binding	GO:0000184//nuclear-transcribed mRNA catabolic process, nonsense-mediated decay;GO:0002181//cytoplasmic translation;GO:0006412//translation;GO:0006413//translational initiation;GO:0006614//SRP-dependent cotranslational protein targeting to membrane;GO:0019083//viral transcription
0	ENSG00000149273	RPS3	71.8846737057471	38.8525717874973	0.887674112377627	0	0	ribosomal protein S3 [Source:HGNC Symbol;Acc:HGNC:10420]	Human Diseases;Human Diseases;Genetic Information Processing	Infectious diseases;Infectious diseases;Translation	ko05130//Pathogenic Escherichia coli infection;ko05132//Salmonella infection;ko03010//Ribosome	K02985;K02985;K02985	GO:0005634//nucleus;GO:0005654//nucleoplasm;GO:0005730//nucleolus;GO:0005737//cytoplasm;GO:0005739//mitochondrion;GO:0005743//mitochondrial inner membrane;GO:0005759//mitochondrial matrix;GO:0005783//endoplasmic reticulum;GO:0005819//spindle;GO:0005829//cytosol;GO:0005840//ribosome;GO:0005844//polysome;GO:0005856//cytoskeleton;GO:0005886//plasma membrane;GO:0005925//focal adhesion;GO:0014069//postsynaptic density;GO:0015935//small ribosomal subunit;GO:0016020//membrane;GO:0022626//cytosolic ribosome;GO:0022627//cytosolic small ribosomal subunit;GO:0032587//ruffle membrane;GO:0070062//extracellular exosome;GO:0071159//NF-kappaB complex;GO:0072686//mitotic spindle;GO:1990904//ribonucleoprotein complex	GO:0000977//RNA polymerase II regulatory region sequence-specific DNA binding;GO:0003677//DNA binding;GO:0003684//damaged DNA binding;GO:0003723//RNA binding;GO:0003729//mRNA binding;GO:0003735//structural constituent of ribosome;GO:0003906//DNA-(apurinic or apyrimidinic site) endonuclease activity;GO:0004520//endodeoxyribonuclease activity;GO:0005515//protein binding;GO:0008017//microtubule binding;GO:0008134//transcription factor binding;GO:0015631//tubulin binding;GO:0016829//lyase activity;GO:0019899//enzyme binding;GO:0019900//kinase binding;GO:0019901//protein kinase binding;GO:0030544//Hsp70 protein binding;GO:0032357//oxidized purine DNA binding;GO:0032358//oxidized pyrimidine DNA binding;GO:0044390//ubiquitin-like protein conjugating enzyme binding;GO:0044877//protein-containing complex binding;GO:0051018//protein kinase A binding;GO:0051536//iron-sulfur cluster binding;GO:0051879//Hsp90 protein binding;GO:0070181//small ribosomal subunit rRNA binding;GO:0097100//supercoiled DNA binding;GO:0140078//class I DNA-(apurinic or apyrimidinic site) endonuclease activity	GO:0000184//nuclear-transcribed mRNA catabolic process, nonsense-mediated decay;GO:0002181//cytoplasmic translation;GO:0006281//DNA repair;GO:0006412//translation;GO:0006413//translational initiation;GO:0006417//regulation of translation;GO:0006614//SRP-dependent cotranslational protein targeting to membrane;GO:0006915//apoptotic process;GO:0006974//cellular response to DNA damage stimulus;GO:0007049//cell cycle;GO:0007059//chromosome segregation;GO:0010628//positive regulation of gene expression;GO:0017148//negative regulation of translation;GO:0019083//viral transcription;GO:0031116//positive regulation of microtubule polymerization;GO:0031334//positive regulation of protein complex assembly;GO:0031397//negative regulation of protein ubiquitination;GO:0032079//positive regulation of endodeoxyribonuclease activity;GO:0032743//positive regulation of interleukin-2 production;GO:0034614//cellular response to reactive oxygen species;GO:0042104//positive regulation of activated T cell proliferation;GO:0042769//DNA damage response, detection of DNA damage;GO:0042981//regulation of apoptotic process;GO:0043507//positive regulation of JUN kinase activity;GO:0045738//negative regulation of DNA repair;GO:0045739//positive regulation of DNA repair;GO:0050862//positive regulation of T cell receptor signaling pathway;GO:0051092//positive regulation of NF-kappaB transcription factor activity;GO:0051225//spindle assembly;GO:0051301//cell division;GO:0061481//response to TNF agonist;GO:0070301//cellular response to hydrogen peroxide;GO:0071356//cellular response to tumor necrosis factor;GO:1901224//positive regulation of NIK/NF-kappaB signaling;GO:1902231//positive regulation of intrinsic apoptotic signaling pathway in response to DNA damage;GO:1902546//positive regulation of DNA N-glycosylase activity;GO:1905053//positive regulation of base-excision repair;GO:2001235//positive regulation of apoptotic signaling pathway;GO:2001272//positive regulation of cysteine-type endopeptidase activity involved in execution phase of apoptosis
0	ENSG00000100316	RPL3	54.3793203080841	29.4423798772188	0.885163827521441	0	0	ribosomal protein L3 [Source:HGNC Symbol;Acc:HGNC:10332]	Genetic Information Processing	Translation	ko03010//Ribosome	K02925	GO:0005634//nucleus;GO:0005730//nucleolus;GO:0005737//cytoplasm;GO:0005829//cytosol;GO:0005840//ribosome;GO:0005925//focal adhesion;GO:0022625//cytosolic large ribosomal subunit;GO:0022626//cytosolic ribosome;GO:0032991//protein-containing complex;GO:0070062//extracellular exosome	GO:0003723//RNA binding;GO:0003735//structural constituent of ribosome;GO:0005515//protein binding	GO:0000027//ribosomal large subunit assembly;GO:0000184//nuclear-transcribed mRNA catabolic process, nonsense-mediated decay;GO:0002181//cytoplasmic translation;GO:0006364//rRNA processing;GO:0006412//translation;GO:0006413//translational initiation;GO:0006614//SRP-dependent cotranslational protein targeting to membrane;GO:0019083//viral transcription;GO:0071353//cellular response to interleukin-4

5.2 上调基因表达分布

Fig 5-2-1 标记基因表达热图

Fig 5-2-2 标记基因表达分布气泡图

5.3 GO富集分析

       Gene Ontology（简称GO）是一个国际标准化的基因功能分类体系，提供了一套动态更新的标准词汇表（controlled vocabulary）来全面描述生物体中基因和基因产物的属性。GO总共有三个ontology（本体），分别描述基因的分子功能（molecular function）、细胞组分（cellular component）、参与的生物过程（biological process）。GO的基本单位是term（词条、节点），每个term都对应一个属性。 GO功能分析一方面给出基因的GO功能分类注释；另一方面给出基因的GO功能显著性富集分析。 首先，我们将基因向GO数据库(http://www.geneontology.org/)的各term映射，并计算每个term的基因数，从而得到具有某个GO功能的基因列表及基因数目统计。然后应用超几何检验，找出与整个基因组背景相比，在基因中显著富集的GO条目。

GO富集圈图：(第一圈：富集前20的GOterm,圈外为基因数目的坐标尺。不同的颜色代表不同的Ontology; 第二圈：背景基因中该GOterm的数目以及Q值。基因越多条形越长，Q值越小颜色越红； 第三圈：该GOterm差异基因数量 第四圈：各GOterm的RichFactor值(该GOterm中差异数量除以所有数量),背景网格线，每一格代表0.1)

GO 富集分类柱状图：（横坐标为二级GOterm，纵坐标为该term里的基因数量,不同颜色表色不同类型GOterm）

GO富集气泡图：(利用Q值最小的前20个GOterm来作图，纵坐标为GOterm，横坐标为富集因子(该GOterm中差异数量除以所有数量)，大小表示数量多少，颜色越红Q值越小)");

GO富集条形图：(利用Q值最小的前20个GOterm来作图，纵坐标为GOterm，横坐标为该GOterm数目占所有差异数目的百分比，颜色越深Q值越小，柱子上的数值为该GOterm数量及Q值");

5.4 KO富集分析

       在生物体内，不同基因相互协调行使其生物学，基于Pathway的分析有助于更进一步了解基因的生物学功能。KEGG是有关Pathway的主要公共数据库。 Pathway显著性富集分析以KEGG Pathway为单位，应用超几何检验，找出与整个基因组背景相比，在基因中显著性富集的Pathway。通过Pathway显著性富集能确定基因参与的最主要生化代谢途径和信号转导途径。

所有趋势pathway统计如下所示：

KO富集圈图：(第一圈：富集前20的pathway,圈外为基因数目的坐标尺。不同的颜色代表不同的A class; 第二圈：背景基因中该pathway的数目以及Q值。基因越多条形越长，Q值越小颜色越红； 第三圈：该pathway差异基因数量 第四圈：各pathway的RichFactor值(该pathway中差异数量除以所有数量),背景网格线，每一格代表0.1)

KO富集气泡图：(利用Q值最小的前20个pathway来作图，纵坐标为pathway，横坐标为富集因子(该pathway中差异数量除以所有数量)，大小表示数量多少，颜色越红Q值越小)");

KO富集条形图：(利用Q值最小的前20个pathway来作图，纵坐标为pathway，横坐标为该pathway数目占所有差异数目的百分比，颜色越深Q值越小，柱子上的数值为该pathway数量及Q值");

5.5 DO富集分析

       DO(Disease Ontology)是描述基因功能与疾病相关的数据库。我们将基因向DO数据库(http://disease-ontology.org/)的各term映射，并计算每个term的基因数，从而得到具有某个DO功能的基因列表及基因数目统计。然后应用超几何检验，找出与整个基因组背景相比，在基因中显著富集的DO条目。

DO富集圈图：(第一圈：富集前20的DOterm,圈外为基因数目的坐标尺。 第二圈：背景基因中该DOterm的数目以及Q值。基因越多条形越长，Q值越小颜色越红； 第三圈：该DOterm差异基因数量 第四圈：各DOterm的RichFactor值(该DOterm中差异数量除以所有数量),背景网格线，每一格代表0.1)

DO富集气泡图：(利用Q值最小的前20个DOterm来作图，纵坐标为DOterm，横坐标为富集因子(该DOterm中差异数量除以所有数量)，大小表示数量多少，颜色越红Q值越小)");

DO富集条形图：(利用Q值最小的前20个DOterm来作图，纵坐标为DOterm，横坐标为该DOterm数目占所有差异数目的百分比，颜色越深Q值越小，柱子上的数值为该DOterm数量及Q值");

5.6 Reactome富集分析

       Reactome数据库汇集了部分物种各项反应及生物学通路。我们将基因向Reactome数据库(https://reactome.org/)的各term映射，并计算每个term的基因数，从而得到具有某个Reactome功能的基因列表及基因数目统计。然后应用超几何检验，找出与整个基因组背景相比，在基因中显著富集的Reactome条目。

Reactome富集圈图：(第一圈：富集前20的Reactome通路,圈外为基因数目的坐标尺。 第二圈：背景基因中该Reactome通路的数目以及Q值。基因越多条形越长，Q值越小颜色越红； 第三圈：该Reactome通路差异基因数量 第四圈：各Reactome通路的RichFactor值(该Reactome通路中差异数量除以所有数量),背景网格线，每一格代表0.1)

Reactome富集气泡图：(利用Q值最小的前20个Reactome通路来作图，纵坐标为Reactome通路，横坐标为富集因子(该Reactome通路中差异数量除以所有数量)，大小表示数量多少，颜色越红Q值越小)");

Reactome富集条形图：(利用Q值最小的前20个Reactome通路来作图，纵坐标为Reactome通路，横坐标为该Reactome通路数目占所有差异数目的百分比，颜色越深Q值越小，柱子上的数值为该Reactome通路数量及Q值");

5.7 上调基因蛋白质互作网络分析

通过string数据库^[10]，我们可以获得上调基因构建蛋白质互作关系信息(3.MarkerGene/String)，然后利用Cytoscape构建蛋白质互作网络图。

String蛋白质互作调控网络图

注：依据系统配置及浏览器不同，如果标记基因数量过多该图可能不能正常加载，请使用桌面版Cytoscape软件

Cytoscape官方手册：http://manual.cytoscape.org/en/stable/index.html
Cytoscape使用教程：http://www.omicshare.com/class/home/index/classdetail?id=14

广州基迪奥生物科技有限公司

6 GSVA分析

基于传统的超几何检验的富集分析，往往需要用到显著差异基因集数据。当单个基因变化较为微弱时，基于传统富集分析得到结果可能会很少，甚至没有结果。GSVA分析（Gene Set Variation Analysis）^[11]能够有效弥补传统富集分析对微效基因的有效信息挖据不足等问题，更为全面地对某一功能单位的调节作用进行解释。GSVA分析反映了某一个细胞亚群相对于所有细胞过表达的通路信息。GSVA原理如下：

• 将每个基因在所有cluster的表达量分布情况进行统计，然后将基因在每个样本中按照表达量从高到低进行排序
• 分析特定基因集是否在所有基因中的排名更为靠前或靠后，然后对基因集在每个样本中的富集程度进行打分，即富集分数（Enrichment Score, ES）

我们对MSigDB数据库的八个数据集的每个通路进行GSVA分析

MSigDB数据库各数据集在各细胞富集程度表:

• H: 4.GSVA/H.gsva.xls
• C1: 4.GSVA/C1.gsva.xls
• C2: 4.GSVA/C2.gsva.xls
• C3: 4.GSVA/C3.gsva.xls
• C4: 4.GSVA/C4.gsva.xls
• C5: 4.GSVA/C5.gsva.xls
• C6: 4.GSVA/C6.gsva.xls
• C7: 4.GSVA/C7.gsva.xls

广州基迪奥生物科技有限公司

7 转录因子注释

转录因子是调控基因表达的重要元件，其表达情况与细胞的下游基因表达和上游表观调控息息相关。为了方便转录因子分析的进行，我们使用animalTFDB（对动物样本）或者plantTFDB（对植物样本）对样本中所有有表达的转录因子进行注释。

Tab 7-0-1 转录因子注释表

gene_id	TF_family	Gene_name	Cluster 0	Cluster 1	Cluster 2	Cluster 3	Cluster 4	Cluster 5	Cluster 6	Cluster 7	Cluster 8	Cluster 9	Cluster 10	Cluster 11	Cluster 12	Cluster 13	Cluster 14	Cluster 15	Cluster 16	Cluster 17	Description	KEGG_A_class	KEGG_B_class	Pathway	K_ID	GO Component	GO Function	GO Process
ENSG00000184895	HMG	SRY	0	0	0	0	0	0	0.00190560216047843	0	0	0	0	0	0	0	0	0	0	0	sex determining region Y [Source:HGNC Symbol;Acc:HGNC:11311]	-	-	-	-	GO:0000785//chromatin;GO:0005634//nucleus;GO:0005654//nucleoplasm;GO:0005737//cytoplasm;GO:0016607//nuclear speck	GO:0000978//RNA polymerase II proximal promoter sequence-specific DNA binding;GO:0000981//DNA-binding transcription factor activity, RNA polymerase II-specific;GO:0003677//DNA binding;GO:0003700//DNA-binding transcription factor activity;GO:0005516//calmodulin binding;GO:0008134//transcription factor binding	GO:0000122//negative regulation of transcription by RNA polymerase II;GO:0006355//regulation of transcription, DNA-templated;GO:0007548//sex differentiation;GO:0009653//anatomical structure morphogenesis;GO:0010628//positive regulation of gene expression;GO:0030154//cell differentiation;GO:0030238//male sex determination;GO:0045893//positive regulation of transcription, DNA-templated;GO:0045944//positive regulation of transcription by RNA polymerase II;GO:2000020//positive regulation of male gonad development
ENSG00000067646	zf-C2H2	ZFY	0.22791427073911	0.247615752293365	0.321654162325371	0.165435313137201	0.168520579369056	0.296147648742535	0.0832645917611452	0.303790240465556	0.238270718480788	0.14583194434532	0.104361407105929	0.227124574737163	0.29687074277983	0.273902268684596	0.0976225986478191	0.251187125208459	0.154057093558873	0.351837832358251	zinc finger protein Y-linked [Source:HGNC Symbol;Acc:HGNC:12870]	-	-	-	-	GO:0005634//nucleus;GO:0005654//nucleoplasm;GO:0005730//nucleolus	GO:0000981//DNA-binding transcription factor activity, RNA polymerase II-specific;GO:0003677//DNA binding;GO:0005515//protein binding;GO:0043565//sequence-specific DNA binding;GO:0046872//metal ion binding	GO:0006355//regulation of transcription, DNA-templated;GO:0006357//regulation of transcription by RNA polymerase II
ENSG00000189403	HMG	HMGB1	6.09110863724643	9.12409728807421	7.32328130304392	4.62803791887348	4.19500265674649	9.53696051028423	8.08133128594316	6.67833861520736	23.5916928312179	9.28628525302923	10.1479907421655	6.09796713910564	9.12850880681579	7.58643180526377	5.57381285357705	9.15324301367061	3.67644556112251	7.95279003891913	high mobility group box 1 [Source:HGNC Symbol;Acc:HGNC:4983]	Cellular Processes;Cellular Processes;Genetic Information Processing	Cell growth and death;Transport and catabolism;Replication and repair	ko04217//Necroptosis;ko04140//Autophagy - animal;ko03410//Base excision repair	K10802;K10802;K10802	GO:0000793//condensed chromosome;GO:0005576//extracellular region;GO:0005615//extracellular space;GO:0005634//nucleus;GO:0005654//nucleoplasm;GO:0005694//chromosome;GO:0005737//cytoplasm;GO:0005768//endosome;GO:0005769//early endosome;GO:0005793//endoplasmic reticulum-Golgi intermediate compartment;GO:0005886//plasma membrane;GO:0009986//cell surface;GO:0016020//membrane;GO:0017053//transcriptional repressor complex;GO:0034774//secretory granule lumen;GO:0035868//alphav-beta3 integrin-HMGB1 complex;GO:0043005//neuron projection;GO:1904813//ficolin-1-rich granule lumen	GO:0000400//four-way junction DNA binding;GO:0000405//bubble DNA binding;GO:0000976//transcription regulatory region sequence-specific DNA binding;GO:0001530//lipopolysaccharide binding;GO:0001786//phosphatidylserine binding;GO:0003677//DNA binding;GO:0003684//damaged DNA binding;GO:0003690//double-stranded DNA binding;GO:0003697//single-stranded DNA binding;GO:0003713//transcription coactivator activity;GO:0003723//RNA binding;GO:0003725//double-stranded RNA binding;GO:0003727//single-stranded RNA binding;GO:0005125//cytokine activity;GO:0005178//integrin binding;GO:0005515//protein binding;GO:0008134//transcription factor binding;GO:0008301//DNA binding, bending;GO:0010858//calcium-dependent protein kinase regulator activity;GO:0016829//lyase activity;GO:0019958//C-X-C chemokine binding;GO:0030295//protein kinase activator activity;GO:0042056//chemoattractant activity;GO:0050786//RAGE receptor binding;GO:0070182//DNA polymerase binding;GO:0070491//repressing transcription factor binding;GO:0097100//supercoiled DNA binding	GO:0000122//negative regulation of transcription by RNA polymerase II;GO:0001654//eye development;GO:0001773//myeloid dendritic cell activation;GO:0001934//positive regulation of protein phosphorylation;GO:0001935//endothelial cell proliferation;GO:0002218//activation of innate immune response;GO:0002224//toll-like receptor signaling pathway;GO:0002250//adaptive immune response;GO:0002270//plasmacytoid dendritic cell activation;GO:0002281//macrophage activation involved in immune response;GO:0002376//immune system process;GO:0002407//dendritic cell chemotaxis;GO:0002437//inflammatory response to antigenic stimulus;GO:0002643//regulation of tolerance induction;GO:0002840//regulation of T cell mediated immune response to tumor cell;GO:0006265//DNA topological change;GO:0006281//DNA repair;GO:0006284//base-excision repair;GO:0006303//double-strand break repair via nonhomologous end joining;GO:0006309//apoptotic DNA fragmentation;GO:0006310//DNA recombination;GO:0006342//chromatin silencing;GO:0006357//regulation of transcription by RNA polymerase II;GO:0006914//autophagy;GO:0006935//chemotaxis;GO:0006954//inflammatory response;GO:0006974//cellular response to DNA damage stimulus;GO:0007165//signal transduction;GO:0007204//positive regulation of cytosolic calcium ion concentration;GO:0010508//positive regulation of autophagy;GO:0016032//viral process;GO:0017055//negative regulation of RNA polymerase II transcriptional preinitiation complex assembly;GO:0030324//lung development;GO:0031175//neuron projection development;GO:0031497//chromatin assembly;GO:0032072//regulation of restriction endodeoxyribonuclease activity;GO:0032147//activation of protein kinase activity;GO:0032392//DNA geometric change;GO:0032425//positive regulation of mismatch repair;GO:0032689//negative regulation of interferon-gamma production;GO:0032727//positive regulation of interferon-alpha production;GO:0032728//positive regulation of interferon-beta production;GO:0032731//positive regulation of interleukin-1 beta production;GO:0032732//positive regulation of interleukin-1 production;GO:0032733//positive regulation of interleukin-10 production;GO:0032735//positive regulation of interleukin-12 production;GO:0032755//positive regulation of interleukin-6 production;GO:0032757//positive regulation of interleukin-8 production;GO:0032760//positive regulation of tumor necrosis factor production;GO:0033151//V(D)J recombination;GO:0034137//positive regulation of toll-like receptor 2 signaling pathway;GO:0034145//positive regulation of toll-like receptor 4 signaling pathway;GO:0034165//positive regulation of toll-like receptor 9 signaling pathway;GO:0035711//T-helper 1 cell activation;GO:0035767//endothelial cell chemotaxis;GO:0042104//positive regulation of activated T cell proliferation;GO:0043065//positive regulation of apoptotic process;GO:0043277//apoptotic cell clearance;GO:0043280//positive regulation of cysteine-type endopeptidase activity involved in apoptotic process;GO:0043312//neutrophil degranulation;GO:0043371//negative regulation of CD4-positive, alpha-beta T cell differentiation;GO:0043388//positive regulation of DNA binding;GO:0043410//positive regulation of MAPK cascade;GO:0043536//positive regulation of blood vessel endothelial cell migration;GO:0043537//negative regulation of blood vessel endothelial cell migration;GO:0045063//T-helper 1 cell differentiation;GO:0045087//innate immune response;GO:0045089//positive regulation of innate immune response;GO:0045639//positive regulation of myeloid cell differentiation;GO:0045819//positive regulation of glycogen catabolic process;GO:0045859//regulation of protein kinase activity;GO:0045944//positive regulation of transcription by RNA polymerase II;GO:0046330//positive regulation of JNK cascade;GO:0050918//positive chemotaxis;GO:0051106//positive regulation of DNA ligation;GO:0051384//response to glucocorticoid;GO:0070374//positive regulation of ERK1 and ERK2 cascade;GO:0071222//cellular response to lipopolysaccharide;GO:0071639//positive regulation of monocyte chemotactic protein-1 production;GO:0090026//positive regulation of monocyte chemotaxis;GO:0090303//positive regulation of wound healing;GO:0097350//neutrophil clearance;GO:0098761//cellular response to interleukin-7;GO:1901224//positive regulation of NIK/NF-kappaB signaling;GO:1903672//positive regulation of sprouting angiogenesis;GO:1905564//positive regulation of vascular endothelial cell proliferation;GO:2000343//positive regulation of chemokine (C-X-C motif) ligand 2 production;GO:2000426//negative regulation of apoptotic cell clearance;GO:2000819//regulation of nucleotide-excision repair;GO:2001200//positive regulation of dendritic cell differentiation
ENSG00000120669	bHLH	SOHLH2	0	0	0	3.06384939587018e-04	0	0	2.92424115795739e-04	0	0	0	0	0	0	0	0	0	0	0	spermatogenesis and oogenesis specific basic helix-loop-helix 2 [Source:HGNC Symbol;Acc:HGNC:26026]	-	-	-	-	GO:0000785//chromatin;GO:0005634//nucleus;GO:0005737//cytoplasm	GO:0000978//RNA polymerase II proximal promoter sequence-specific DNA binding;GO:0000981//DNA-binding transcription factor activity, RNA polymerase II-specific;GO:0003677//DNA binding;GO:0042803//protein homodimerization activity;GO:0046982//protein heterodimerization activity;GO:0046983//protein dimerization activity;GO:1990837//sequence-specific double-stranded DNA binding	GO:0006355//regulation of transcription, DNA-templated;GO:0006357//regulation of transcription by RNA polymerase II;GO:0007275//multicellular organism development;GO:0007283//spermatogenesis;GO:0009994//oocyte differentiation;GO:0030154//cell differentiation;GO:0048477//oogenesis
ENSG00000136169	MBD	SETDB2	0.298965595310527	0.257438699646651	0.24876868756027	0.309953238385754	0.265181240623282	0.263117957097997	0.0580096897185941	0.281931588075105	0.136156306190823	0.137265069864101	0.244971140237245	0.369101750191004	0.496049152284623	0.294506738905806	0.271964646656462	0.0923224827800485	0.779349603141444	0.384201717228608	SET domain bifurcated histone lysine methyltransferase 2 [Source:HGNC Symbol;Acc:HGNC:20263]	Metabolism;Metabolism	Global and overview maps;Amino acid metabolism	ko01100//Metabolic pathways;ko00310//Lysine degradation	K18494;K18494	GO:0005634//nucleus;GO:0005654//nucleoplasm;GO:0005694//chromosome;GO:0005829//cytosol	GO:0003677//DNA binding;GO:0005515//protein binding;GO:0008168//methyltransferase activity;GO:0008270//zinc ion binding;GO:0016740//transferase activity;GO:0018024//histone-lysine N-methyltransferase activity;GO:0046872//metal ion binding;GO:0046974//histone methyltransferase activity (H3-K9 specific)	GO:0000278//mitotic cell cycle;GO:0001947//heart looping;GO:0006325//chromatin organization;GO:0007049//cell cycle;GO:0007059//chromosome segregation;GO:0007275//multicellular organism development;GO:0010629//negative regulation of gene expression;GO:0032259//methylation;GO:0034968//histone lysine methylation;GO:0045892//negative regulation of transcription, DNA-templated;GO:0051301//cell division;GO:0051567//histone H3-K9 methylation;GO:0070828//heterochromatin organization;GO:0070986//left/right axis specification;GO:0090309//positive regulation of methylation-dependent chromatin silencing
ENSG00000122034	zf-C2H2	GTF3A	2.44091255649724	2.26166734533229	2.06315346131925	1.3086859967033	1.48420274514704	2.25955489351625	2.14039504597184	2.62405829603118	2.74102314786523	3.47748522584798	2.08627746530363	1.74981539369249	2.85707125394204	2.32250188149862	2.06221091845267	2.85406145480385	0.337065413089583	1.44715693577479	general transcription factor IIIA [Source:HGNC Symbol;Acc:HGNC:4662]	-	-	-	-	GO:0005634//nucleus;GO:0005654//nucleoplasm	GO:0003677//DNA binding;GO:0003723//RNA binding;GO:0008097//5S rRNA binding;GO:0046872//metal ion binding	GO:0006383//transcription by RNA polymerase III;GO:0009303//rRNA transcription;GO:0042254//ribosome biogenesis;GO:0042273//ribosomal large subunit biogenesis
ENSG00000120690	ETS	ELF1	1.89171429215427	2.37640740723066	2.12515190946643	1.1558680004652	1.1172900628659	2.43088567872987	0.493836048574721	1.94433071198443	1.45321884653274	1.37391264068418	0.697204074929624	2.15742640612546	1.70334260102848	3.49035169195902	1.16836460020845	2.71923004279811	0.247159878082571	3.39915663392579	E74 like ETS transcription factor 1 [Source:HGNC Symbol;Acc:HGNC:3316]	Cellular Processes	Cell growth and death	ko04214//Apoptosis - fly	K09428	GO:0000785//chromatin;GO:0005634//nucleus;GO:0005654//nucleoplasm	GO:0000978//RNA polymerase II proximal promoter sequence-specific DNA binding;GO:0000981//DNA-binding transcription factor activity, RNA polymerase II-specific;GO:0001228//DNA-binding transcription activator activity, RNA polymerase II-specific;GO:0003677//DNA binding;GO:0003700//DNA-binding transcription factor activity;GO:0005515//protein binding;GO:0043565//sequence-specific DNA binding;GO:1990837//sequence-specific double-stranded DNA binding	GO:0001959//regulation of cytokine-mediated signaling pathway;GO:0006355//regulation of transcription, DNA-templated;GO:0006357//regulation of transcription by RNA polymerase II;GO:0030154//cell differentiation;GO:0045893//positive regulation of transcription, DNA-templated;GO:0045944//positive regulation of transcription by RNA polymerase II;GO:0050855//regulation of B cell receptor signaling pathway
ENSG00000102804	TSC22	TSC22D1	0.197060534386352	0.542554064712421	0.315784734733659	0.135827531431084	0.210580303190102	1.63046886878926	2.4196886765296	0.278789208435533	0.476534482533483	1.51202633677024	0.186467740386242	0.154152125212726	0.294840294356709	0.472923980614282	0.153225561644462	0.577237527049193	0.550623960856073	2.75204179339859	TSC22 domain family member 1 [Source:HGNC Symbol;Acc:HGNC:16826]	-	-	-	-	GO:0005634//nucleus;GO:0005737//cytoplasm	GO:0005515//protein binding	GO:0006357//regulation of transcription by RNA polymerase II;GO:0006366//transcription by RNA polymerase II
ENSG00000276644	DACH	DACH1	0	0	0	0	0	0	8.67041413489545e-04	0	0	0	0	0	0	0	0.0141482739105829	0	0	0.575366896364155	dachshund family transcription factor 1 [Source:HGNC Symbol;Acc:HGNC:2663]	-	-	-	-	GO:0005634//nucleus;GO:0005667//transcription factor complex;GO:0005737//cytoplasm	GO:0000977//RNA polymerase II regulatory region sequence-specific DNA binding;GO:0000978//RNA polymerase II proximal promoter sequence-specific DNA binding;GO:0000981//DNA-binding transcription factor activity, RNA polymerase II-specific;GO:0001227//DNA-binding transcription repressor activity, RNA polymerase II-specific;GO:0003677//DNA binding;GO:0003700//DNA-binding transcription factor activity;GO:0005515//protein binding	GO:0000122//negative regulation of transcription by RNA polymerase II;GO:0001967//suckling behavior;GO:0006355//regulation of transcription, DNA-templated;GO:0006357//regulation of transcription by RNA polymerase II;GO:0007275//multicellular organism development;GO:0007585//respiratory gaseous exchange;GO:0008283//cell proliferation;GO:0010944//negative regulation of transcription by competitive promoter binding;GO:0030336//negative regulation of cell migration;GO:0033262//regulation of nuclear cell cycle DNA replication;GO:0045892//negative regulation of transcription, DNA-templated;GO:0046545//development of primary female sexual characteristics;GO:0048147//negative regulation of fibroblast proliferation;GO:0060244//negative regulation of cell proliferation involved in contact inhibition;GO:2000279//negative regulation of DNA biosynthetic process
ENSG00000102554	zf-C2H2	KLF5	0.00801742949029745	6.45879049459803e-04	0.00651859552230734	5.36908139312629e-04	0.003317052965609	0.0016125547059184	0.0506108465024462	0	0.00436188422735778	0	0.00214456743538686	0	0	0.0160605940226463	0	0	0	0	Kruppel like factor 5 [Source:HGNC Symbol;Acc:HGNC:6349]	-	-	-	-	GO:0000785//chromatin;GO:0005634//nucleus;GO:0005654//nucleoplasm;GO:0005667//transcription factor complex;GO:0005794//Golgi apparatus;GO:0043231//intracellular membrane-bounded organelle	GO:0000978//RNA polymerase II proximal promoter sequence-specific DNA binding;GO:0000981//DNA-binding transcription factor activity, RNA polymerase II-specific;GO:0001228//DNA-binding transcription activator activity, RNA polymerase II-specific;GO:0003677//DNA binding;GO:0003700//DNA-binding transcription factor activity;GO:0005515//protein binding;GO:0008134//transcription factor binding;GO:0043426//MRF binding;GO:0043565//sequence-specific DNA binding;GO:0046872//metal ion binding;GO:1990837//sequence-specific double-stranded DNA binding	GO:0000122//negative regulation of transcription by RNA polymerase II;GO:0001525//angiogenesis;GO:0006355//regulation of transcription, DNA-templated;GO:0006357//regulation of transcription by RNA polymerase II;GO:0008284//positive regulation of cell proliferation;GO:0010468//regulation of gene expression;GO:0014816//skeletal muscle satellite cell differentiation;GO:0014901//satellite cell activation involved in skeletal muscle regeneration;GO:0014908//myotube differentiation involved in skeletal muscle regeneration;GO:0030033//microvillus assembly;GO:0032534//regulation of microvillus assembly;GO:0035914//skeletal muscle cell differentiation;GO:0043403//skeletal muscle tissue regeneration;GO:0045600//positive regulation of fat cell differentiation;GO:0045893//positive regulation of transcription, DNA-templated;GO:0045944//positive regulation of transcription by RNA polymerase II;GO:0060576//intestinal epithelial cell development;GO:0061586//positive regulation of transcription by transcription factor localization;GO:0071407//cellular response to organic cyclic compound;GO:0099156//cell-cell signaling via exosome;GO:1901653//cellular response to peptide;GO:1902895//positive regulation of pri-miRNA transcription by RNA polymerase II;GO:1990830//cellular response to leukemia inhibitory factor
ENSG00000169548	Others	ZNF280A	0	0	0	4.4552717448448e-04	0	0	0.0296570664884806	0	0	0	0	0	0	0	0	0	0	0	zinc finger protein 280A [Source:HGNC Symbol;Acc:HGNC:18597]	-	-	-	-	GO:0005634//nucleus	GO:0000978//RNA polymerase II proximal promoter sequence-specific DNA binding;GO:0000981//DNA-binding transcription factor activity, RNA polymerase II-specific;GO:0003677//DNA binding;GO:0005515//protein binding;GO:0046872//metal ion binding	GO:0006355//regulation of transcription, DNA-templated;GO:0006357//regulation of transcription by RNA polymerase II
ENSG00000159086	GCFC	PAXBP1	0.479329743665866	0.669762104894683	0.729590534228172	0.403528010408559	0.325370449462247	0.705136779003875	0.214571303612495	0.546876022913245	0.598908891224767	0.523525290561422	0.279054104055501	0.524554190663372	0.577185519915927	0.544888846662858	0.497749123416388	0.628951615957324	2.63331611556925	0.537819848705888	PAX3 and PAX7 binding protein 1 [Source:HGNC Symbol;Acc:HGNC:13579]	-	-	-	-	GO:0005634//nucleus;GO:0005829//cytosol	GO:0003677//DNA binding;GO:0008134//transcription factor binding	GO:0000398//mRNA splicing, via spliceosome;GO:0006355//regulation of transcription, DNA-templated;GO:0007517//muscle organ development;GO:0014842//regulation of skeletal muscle satellite cell proliferation;GO:0031062//positive regulation of histone methylation;GO:0045944//positive regulation of transcription by RNA polymerase II;GO:2000288//positive regulation of myoblast proliferation
ENSG00000152192	Pou	POU4F1	0	0.00467302144299479	0.00237866885884789	0	0	0	0	0	7.37858174804504e-04	0	0	0.0127903407346772	0	0	0	0	0	0	POU class 4 homeobox 1 [Source:HGNC Symbol;Acc:HGNC:9218]	-	-	-	-	GO:0000785//chromatin;GO:0005634//nucleus;GO:0005654//nucleoplasm;GO:0005737//cytoplasm;GO:0043005//neuron projection;GO:0090575//RNA polymerase II transcription factor complex	GO:0000978//RNA polymerase II proximal promoter sequence-specific DNA binding;GO:0000981//DNA-binding transcription factor activity, RNA polymerase II-specific;GO:0001228//DNA-binding transcription activator activity, RNA polymerase II-specific;GO:0003677//DNA binding;GO:0003682//chromatin binding;GO:0003697//single-stranded DNA binding;GO:0003700//DNA-binding transcription factor activity;GO:0005515//protein binding;GO:0043565//sequence-specific DNA binding;GO:0051020//GTPase binding;GO:1990837//sequence-specific double-stranded DNA binding	GO:0000122//negative regulation of transcription by RNA polymerase II;GO:0001967//suckling behavior;GO:0003223//ventricular compact myocardium morphogenesis;GO:0006355//regulation of transcription, DNA-templated;GO:0006357//regulation of transcription by RNA polymerase II;GO:0007275//multicellular organism development;GO:0007399//nervous system development;GO:0007409//axonogenesis;GO:0007416//synapse assembly;GO:0007498//mesoderm development;GO:0007507//heart development;GO:0010628//positive regulation of gene expression;GO:0010629//negative regulation of gene expression;GO:0021535//cell migration in hindbrain;GO:0021559//trigeminal nerve development;GO:0021953//central nervous system neuron differentiation;GO:0021986//habenula development;GO:0030182//neuron differentiation;GO:0031175//neuron projection development;GO:0043065//positive regulation of apoptotic process;GO:0043066//negative regulation of apoptotic process;GO:0043069//negative regulation of programmed cell death;GO:0043524//negative regulation of neuron apoptotic process;GO:0045672//positive regulation of osteoclast differentiation;GO:0045944//positive regulation of transcription by RNA polymerase II;GO:0048665//neuron fate specification;GO:0048880//sensory system development;GO:0048934//peripheral nervous system neuron differentiation;GO:0048935//peripheral nervous system neuron development;GO:0050767//regulation of neurogenesis;GO:0051090//regulation of DNA-binding transcription factor activity;GO:0051355//proprioception involved in equilibrioception;GO:0060384//innervation;GO:0071158//positive regulation of cell cycle arrest;GO:0071345//cellular response to cytokine stimulus;GO:0071392//cellular response to estradiol stimulus;GO:0072332//intrinsic apoptotic signaling pathway by p53 class mediator;GO:1901796//regulation of signal transduction by p53 class mediator;GO:2000679//positive regulation of transcription regulatory region DNA binding;GO:2001208//negative regulation of transcription elongation by RNA polymerase I
ENSG00000173404	zf-C2H2	INSM1	0	0.0020118078584288	0	0	0	0	0	0	9.19565597211877e-04	0	0	0	0	0	0	0.00644354807531219	0	0	INSM transcriptional repressor 1 [Source:HGNC Symbol;Acc:HGNC:6090]	-	-	-	-	GO:0005634//nucleus;GO:0005654//nucleoplasm;GO:0017053//transcriptional repressor complex	GO:0000978//RNA polymerase II proximal promoter sequence-specific DNA binding;GO:0001227//DNA-binding transcription repressor activity, RNA polymerase II-specific;GO:0003677//DNA binding;GO:0003700//DNA-binding transcription factor activity;GO:0030332//cyclin binding;GO:0031490//chromatin DNA binding;GO:0042826//histone deacetylase binding;GO:0046872//metal ion binding	GO:0000122//negative regulation of transcription by RNA polymerase II;GO:0001933//negative regulation of protein phosphorylation;GO:0003309//type B pancreatic cell differentiation;GO:0003310//pancreatic A cell differentiation;GO:0003323//type B pancreatic cell development;GO:0003358//noradrenergic neuron development;GO:0007049//cell cycle;GO:0007275//multicellular organism development;GO:0007399//nervous system development;GO:0008284//positive regulation of cell proliferation;GO:0008285//negative regulation of cell proliferation;GO:0010468//regulation of gene expression;GO:0010564//regulation of cell cycle process;GO:0030154//cell differentiation;GO:0030182//neuron differentiation;GO:0030335//positive regulation of cell migration;GO:0031018//endocrine pancreas development;GO:0035270//endocrine system development;GO:0042421//norepinephrine biosynthetic process;GO:0043254//regulation of protein complex assembly;GO:0045597//positive regulation of cell differentiation;GO:0060290//transdifferentiation;GO:0061104//adrenal chromaffin cell differentiation;GO:0061549//sympathetic ganglion development;GO:0071158//positive regulation of cell cycle arrest;GO:2000179//positive regulation of neural precursor cell proliferation
ENSG00000275004	Others	ZNF280B	0.0340242775007366	0.0496642565641694	0.0421566108415731	0.00878907665733171	0.0180234686424896	0.0279275462657995	0.0536811713668845	0.0374875192772137	0.0398078737348936	0.1010078106866	0.0105142140959282	0.0143134126229439	0.0628875905321772	0.0654539343745955	0.0387585663970937	0.0121213296613785	0	0	zinc finger protein 280B [Source:HGNC Symbol;Acc:HGNC:23022]	-	-	-	-	GO:0005634//nucleus	GO:0000978//RNA polymerase II proximal promoter sequence-specific DNA binding;GO:0000981//DNA-binding transcription factor activity, RNA polymerase II-specific;GO:0003677//DNA binding;GO:0046872//metal ion binding	GO:0006355//regulation of transcription, DNA-templated;GO:0006357//regulation of transcription by RNA polymerase II
ENSG00000088876	zf-C2H2	ZNF343	0.00994664727628606	0.0286010600172701	0.00993234412706922	0.0120926785825235	0.010073542036797	0.0152018770027368	0.0166577202090751	0.0128379271083637	0.0182257191438911	0	0.0200847183331801	0.00641036735892224	0.104309121206333	0.0697885407216135	0.042429614472836	0.0622215012224023	0	0	zinc finger protein 343 [Source:HGNC Symbol;Acc:HGNC:16017]	Human Diseases	Infectious diseases	ko05168//Herpes simplex infection	K09228	GO:0005634//nucleus	GO:0000977//RNA polymerase II regulatory region sequence-specific DNA binding;GO:0000981//DNA-binding transcription factor activity, RNA polymerase II-specific;GO:0001227//DNA-binding transcription repressor activity, RNA polymerase II-specific;GO:0003677//DNA binding;GO:0005515//protein binding;GO:0046872//metal ion binding;GO:1990837//sequence-specific double-stranded DNA binding	GO:0000122//negative regulation of transcription by RNA polymerase II;GO:0006355//regulation of transcription, DNA-templated;GO:0006357//regulation of transcription by RNA polymerase II
ENSG00000100219	TF_bZIP	XBP1	1.60078838008784	0.414619533707969	0.647754086490007	0.980616711985702	1.64419439381704	0.888331076965033	0.930853117857748	1.94902156384977	0.510847730482646	1.62523198112523	1.02927244511211	0.369823000419912	1.49205571614061	0.930939385707075	1.48850916753013	1.56353513731522	0.216295719507711	1.97800515414804	X-box binding protein 1 [Source:HGNC Symbol;Acc:HGNC:12801]	Human Diseases;Genetic Information Processing;Human Diseases;Human Diseases	Neurodegenerative diseases;Folding, sorting and degradation;Endocrine and metabolic diseases;Neurodegenerative disease	ko05010//Alzheimer disease;ko04141//Protein processing in endoplasmic reticulum;ko04932//Non-alcoholic fatty liver disease (NAFLD);ko05017//Spinocerebellar ataxia	K09027;K09027;K09027;K09027	GO:0005634//nucleus;GO:0005654//nucleoplasm;GO:0005737//cytoplasm;GO:0005783//endoplasmic reticulum;GO:0005789//endoplasmic reticulum membrane;GO:0005829//cytosol;GO:0016020//membrane;GO:0016021//integral component of membrane;GO:0030176//integral component of endoplasmic reticulum membrane	GO:0000976//transcription regulatory region sequence-specific DNA binding;GO:0000977//RNA polymerase II regulatory region sequence-specific DNA binding;GO:0000978//RNA polymerase II proximal promoter sequence-specific DNA binding;GO:0000981//DNA-binding transcription factor activity, RNA polymerase II-specific;GO:0000987//proximal promoter sequence-specific DNA binding;GO:0002020//protease binding;GO:0003677//DNA binding;GO:0003700//DNA-binding transcription factor activity;GO:0005515//protein binding;GO:0019901//protein kinase binding;GO:0030331//estrogen receptor binding;GO:0031490//chromatin DNA binding;GO:0031625//ubiquitin protein ligase binding;GO:0042803//protein homodimerization activity;GO:0046982//protein heterodimerization activity;GO:1990837//sequence-specific double-stranded DNA binding	GO:0000122//negative regulation of transcription by RNA polymerase II;GO:0001525//angiogenesis;GO:0001558//regulation of cell growth;GO:0001889//liver development;GO:0001934//positive regulation of protein phosphorylation;GO:0001935//endothelial cell proliferation;GO:0002639//positive regulation of immunoglobulin production;GO:0006355//regulation of transcription, DNA-templated;GO:0006366//transcription by RNA polymerase II;GO:0006511//ubiquitin-dependent protein catabolic process;GO:0006629//lipid metabolic process;GO:0006633//fatty acid biosynthetic process;GO:0006914//autophagy;GO:0006915//apoptotic process;GO:0006955//immune response;GO:0006986//response to unfolded protein;GO:0006990//positive regulation of transcription from RNA polymerase II promoter involved in unfolded protein response;GO:0006996//organelle organization;GO:0007275//multicellular organism development;GO:0007517//muscle organ development;GO:0008284//positive regulation of cell proliferation;GO:0010508//positive regulation of autophagy;GO:0010832//negative regulation of myotube differentiation;GO:0014065//phosphatidylinositol 3-kinase signaling;GO:0015031//protein transport;GO:0030154//cell differentiation;GO:0030335//positive regulation of cell migration;GO:0030512//negative regulation of transforming growth factor beta receptor signaling pathway;GO:0030968//endoplasmic reticulum unfolded protein response;GO:0031062//positive regulation of histone methylation;GO:0031647//regulation of protein stability;GO:0031648//protein destabilization;GO:0031670//cellular response to nutrient;GO:0032008//positive regulation of TOR signaling;GO:0032755//positive regulation of interleukin-6 production;GO:0032869//cellular response to insulin stimulus;GO:0034599//cellular response to oxidative stress;GO:0034976//response to endoplasmic reticulum stress;GO:0035356//cellular triglyceride homeostasis;GO:0035470//positive regulation of vascular wound healing;GO:0035924//cellular response to vascular endothelial growth factor stimulus;GO:0036498//IRE1-mediated unfolded protein response;GO:0036500//ATF6-mediated unfolded protein response;GO:0042149//cellular response to glucose starvation;GO:0042307//positive regulation of protein import into nucleus;GO:0042632//cholesterol homeostasis;GO:0043066//negative regulation of apoptotic process;GO:0045348//positive regulation of MHC class II biosynthetic process;GO:0045579//positive regulation of B cell differentiation;GO:0045582//positive regulation of T cell differentiation;GO:0045600//positive regulation of fat cell differentiation;GO:0045766//positive regulation of angiogenesis;GO:0045944//positive regulation of transcription by RNA polymerase II;GO:0048010//vascular endothelial growth factor receptor signaling pathway;GO:0048666//neuron development;GO:0051897//positive regulation of protein kinase B signaling;GO:0055089//fatty acid homeostasis;GO:0055092//sterol homeostasis;GO:0060394//negative regulation of pathway-restricted SMAD protein phosphorylation;GO:0060612//adipose tissue development;GO:0070373//negative regulation of ERK1 and ERK2 cascade;GO:0071073//positive regulation of phospholipid biosynthetic process;GO:0071222//cellular response to lipopolysaccharide;GO:0071230//cellular response to amino acid stimulus;GO:0071332//cellular response to fructose stimulus;GO:0071333//cellular response to glucose stimulus;GO:0071353//cellular response to interleukin-4;GO:0071375//cellular response to peptide hormone stimulus;GO:0071498//cellular response to fluid shear stress;GO:0071499//cellular response to laminar fluid shear stress;GO:1900100//positive regulation of plasma cell differentiation;GO:1900102//negative regulation of endoplasmic reticulum unfolded protein response;GO:1900103//positive regulation of endoplasmic reticulum unfolded protein response;GO:1901985//positive regulation of protein acetylation;GO:1902236//negative regulation of endoplasmic reticulum stress-induced intrinsic apoptotic signaling pathway;GO:1903071//positive regulation of ER-associated ubiquitin-dependent protein catabolic process;GO:1903489//positive regulation of lactation;GO:1904707//positive regulation of vascular smooth muscle cell proliferation;GO:1904754//positive regulation of vascular associated smooth muscle cell migration;GO:1990418//response to insulin-like growth factor stimulus;GO:1990440//positive regulation of transcription from RNA polymerase II promoter in response to endoplasmic reticulum stress;GO:2000347//positive regulation of hepatocyte proliferation;GO:2000353//positive regulation of endothelial cell apoptotic process
ENSG00000187792	zf-C2H2	ZNF70	0.0126741573561902	0.0356664323347565	0.0157302064234747	0.0294627326686404	0.0134454725975277	0.0185183850025407	0.0747512765888761	0.0261476009524084	0.0259226993819378	0.0868076306091465	0.00380787118527426	0	0	0	0.0267662158627893	0.031368674831953	0	0	zinc finger protein 70 [Source:HGNC Symbol;Acc:HGNC:13140]	-	-	-	-	GO:0005634//nucleus	GO:0000977//RNA polymerase II regulatory region sequence-specific DNA binding;GO:0000981//DNA-binding transcription factor activity, RNA polymerase II-specific;GO:0003677//DNA binding;GO:0046872//metal ion binding	GO:0006357//regulation of transcription by RNA polymerase II
ENSG00000125285	HMG	SOX21	0	0	0	0	0	0	0	0	9.05388692419543e-04	0	0	0	0	0	0	0	0	0	SRY-box transcription factor 21 [Source:HGNC Symbol;Acc:HGNC:11197]	-	-	-	-	GO:0000785//chromatin;GO:0005575//cellular_component;GO:0005634//nucleus	GO:0000978//RNA polymerase II proximal promoter sequence-specific DNA binding;GO:0000981//DNA-binding transcription factor activity, RNA polymerase II-specific;GO:0001228//DNA-binding transcription activator activity, RNA polymerase II-specific;GO:0003677//DNA binding;GO:0003700//DNA-binding transcription factor activity	GO:0001942//hair follicle development;GO:0006355//regulation of transcription, DNA-templated;GO:0006357//regulation of transcription by RNA polymerase II;GO:0009653//anatomical structure morphogenesis;GO:0030154//cell differentiation;GO:0042633//hair cycle;GO:0043588//skin development;GO:0045944//positive regulation of transcription by RNA polymerase II;GO:0048863//stem cell differentiation
ENSG00000215397	zf-C2H2	SCRT2	0	0	0	0.00163468508062707	0	0	0	0	0	0	0	0	0	0	0	0	0	0	scratch family transcriptional repressor 2 [Source:HGNC Symbol;Acc:HGNC:15952]	-	-	-	-	GO:0000785//chromatin;GO:0005634//nucleus	GO:0000977//RNA polymerase II regulatory region sequence-specific DNA binding;GO:0000978//RNA polymerase II proximal promoter sequence-specific DNA binding;GO:0000981//DNA-binding transcription factor activity, RNA polymerase II-specific;GO:0001227//DNA-binding transcription repressor activity, RNA polymerase II-specific;GO:0003677//DNA binding;GO:0046872//metal ion binding;GO:0070888//E-box binding;GO:1990837//sequence-specific double-stranded DNA binding	GO:0000122//negative regulation of transcription by RNA polymerase II;GO:0006355//regulation of transcription, DNA-templated;GO:1902042//negative regulation of extrinsic apoptotic signaling pathway via death domain receptors;GO:2001222//regulation of neuron migration

8 膜蛋白注释

使用TMHMM预测基因的跨膜结构域。

Tab 8-0-1 膜蛋白注释表

GeneID	Length	ExpAA	First60	PredHel	Topology	Gene_name	Cluster 0	Cluster 1	Cluster 2	Cluster 3	Cluster 4	Cluster 5	Cluster 6	Cluster 7	Cluster 8	Cluster 9	Cluster 10	Cluster 11	Cluster 12	Cluster 13	Cluster 14	Cluster 15	Cluster 16	Cluster 17	Description	KEGG_A_class	KEGG_B_class	Pathway	K_ID	GO Component	GO Function	GO Process
ENSG00000000003	245	90.56	25.32	4	i20-42o57-79i92-114o211-233i	TSPAN6	0.00208036738451333	0.00418788740050105	0.00212206094559036	0	0.00200296710804534	0	0.338847267815758	0	0.00330953879874091	0.0679900473534889	0.00123038686438984	0	0	0	0	0	0	0.120273260848648	tetraspanin 6 [Source:HGNC Symbol;Acc:HGNC:11858]	-	-	-	-	GO:0005887//integral component of plasma membrane;GO:0016020//membrane;GO:0016021//integral component of membrane;GO:0070062//extracellular exosome	GO:0005515//protein binding	GO:0039532//negative regulation of viral-induced cytoplasmic pattern recognition receptor signaling pathway;GO:0043123//positive regulation of I-kappaB kinase/NF-kappaB signaling;GO:1901223//negative regulation of NIK/NF-kappaB signaling
ENSG00000000005	317	20.42	20.38	1	i31-50o	TNMD	0	0	0	0	0	0	0.00905414842968636	0	0	0	0	0	0	0	0	0	0	0	tenomodulin [Source:HGNC Symbol;Acc:HGNC:17757]	-	-	-	-	GO:0005634//nucleus;GO:0005635//nuclear envelope;GO:0005737//cytoplasm;GO:0016020//membrane;GO:0016021//integral component of membrane	GO:0005515//protein binding	GO:0001886//endothelial cell morphogenesis;GO:0001937//negative regulation of endothelial cell proliferation;GO:0016525//negative regulation of angiogenesis;GO:0030948//negative regulation of vascular endothelial growth factor receptor signaling pathway;GO:0035990//tendon cell differentiation;GO:0071773//cellular response to BMP stimulus
ENSG00000000419	295	0.02	0.00	0	o	DPM1	0.274110271761413	0.379626594299589	0.262057982850531	0.245697630862007	0.294328586671324	0.347111818572435	0.268396993649914	0.248756956606939	0.447412735912293	0.331934474495252	0.333411040711985	0.324682679909625	0.389938335249662	0.192501707722402	0.197101485645234	0.499605115229635	0.129334316274137	0.281472583811492	dolichyl-phosphate mannosyltransferase subunit 1, catalytic [Source:HGNC Symbol;Acc:HGNC:3005]	Metabolism;Metabolism	Global and overview maps;Glycan biosynthesis and metabolism	ko01100//Metabolic pathways;ko00510//N-Glycan biosynthesis	K00721;K00721	GO:0005634//nucleus;GO:0005783//endoplasmic reticulum;GO:0005789//endoplasmic reticulum membrane;GO:0016020//membrane;GO:0033185//dolichol-phosphate-mannose synthase complex;GO:0043231//intracellular membrane-bounded organelle	GO:0004169//dolichyl-phosphate-mannose-protein mannosyltransferase activity;GO:0004582//dolichyl-phosphate beta-D-mannosyltransferase activity;GO:0005515//protein binding;GO:0005537//mannose binding;GO:0016740//transferase activity;GO:0016757//transferase activity, transferring glycosyl groups;GO:0043178//alcohol binding	GO:0006486//protein glycosylation;GO:0006506//GPI anchor biosynthetic process;GO:0018279//protein N-linked glycosylation via asparagine;GO:0019348//dolichol metabolic process;GO:0019673//GDP-mannose metabolic process;GO:0035268//protein mannosylation;GO:0035269//protein O-linked mannosylation;GO:0097502//mannosylation
ENSG00000000457	742	0.63	0.03	0	o	SCYL3	0.193949397022363	0.211841815529268	0.147468793460387	0.0918355173056356	0.0734831407898222	0.190889055621627	0.0992341310891407	0.140597913223082	0.169327828747789	0.218509102442517	0.0741923200134361	0.201995380690227	0.1517981786149	0.160692432640826	0.209174020051657	0.10777980692049	0.262363898727535	0.208938384070538	SCY1 like pseudokinase 3 [Source:HGNC Symbol;Acc:HGNC:19285]	-	-	-	-	GO:0000139//Golgi membrane;GO:0005737//cytoplasm;GO:0005794//Golgi apparatus;GO:0030027//lamellipodium;GO:0042995//cell projection	GO:0004672//protein kinase activity;GO:0005515//protein binding;GO:0005524//ATP binding;GO:0042802//identical protein binding	GO:0006468//protein phosphorylation;GO:0006954//inflammatory response;GO:0016477//cell migration;GO:0021522//spinal cord motor neuron differentiation;GO:0034613//cellular protein localization;GO:0048666//neuron development
ENSG00000000460	853	0.17	0.00	0	o	C1orf112	0.0359023567476643	0.0608366363670155	0.0558691513434008	0.054910077845424	0.0289579937189582	0.0399126397407848	0.0446155364195468	0.0283562081228327	0.324639171463501	0.0950308472594259	0.0784811332534847	0.0357947733936919	0.0714821830658708	0.00789652395015714	0.0354692673411771	0.0466442499038207	0.330278356829788	0	chromosome 1 open reading frame 112 [Source:HGNC Symbol;Acc:HGNC:25565]	-	-	-	-	-	GO:0005515//protein binding	-
ENSG00000000938	529	0.12	0.00	0	o	FGR	0.00849088936617691	0.0275938408608649	0.287301007028436	0.261684057184661	0.782386739576712	0.111186401942969	0.0105811152280051	0.513001124005948	0.021197896602045	0.107445751057201	0.2259889577394	0.00800690515500568	0.267620538451497	0.188794111475547	0.103194021499526	0.0110203159524584	0.394750589772219	0.221141088014153	FGR proto-oncogene, Src family tyrosine kinase [Source:HGNC Symbol;Acc:HGNC:3697]	Organismal Systems	Immune system	ko04062//Chemokine signaling pathway	K08891	GO:0005576//extracellular region;GO:0005737//cytoplasm;GO:0005739//mitochondrion;GO:0005743//mitochondrial inner membrane;GO:0005758//mitochondrial intermembrane space;GO:0005829//cytosol;GO:0005856//cytoskeleton;GO:0005886//plasma membrane;GO:0015629//actin cytoskeleton;GO:0016020//membrane;GO:0016235//aggresome;GO:0031234//extrinsic component of cytoplasmic side of plasma membrane;GO:0032587//ruffle membrane;GO:0034774//secretory granule lumen;GO:0042995//cell projection;GO:0070062//extracellular exosome	GO:0000166//nucleotide binding;GO:0001784//phosphotyrosine residue binding;GO:0004672//protein kinase activity;GO:0004713//protein tyrosine kinase activity;GO:0004714//transmembrane receptor protein tyrosine kinase activity;GO:0004715//non-membrane spanning protein tyrosine kinase activity;GO:0005102//signaling receptor binding;GO:0005515//protein binding;GO:0005524//ATP binding;GO:0016301//kinase activity;GO:0016740//transferase activity;GO:0019901//protein kinase binding;GO:0034987//immunoglobulin receptor binding;GO:0034988//Fc-gamma receptor I complex binding	GO:0001819//positive regulation of cytokine production;GO:0002376//immune system process;GO:0002768//immune response-regulating cell surface receptor signaling pathway;GO:0002862//negative regulation of inflammatory response to antigenic stimulus;GO:0006468//protein phosphorylation;GO:0007169//transmembrane receptor protein tyrosine kinase signaling pathway;GO:0007229//integrin-mediated signaling pathway;GO:0008360//regulation of cell shape;GO:0009615//response to virus;GO:0014068//positive regulation of phosphatidylinositol 3-kinase signaling;GO:0016310//phosphorylation;GO:0018108//peptidyl-tyrosine phosphorylation;GO:0030154//cell differentiation;GO:0030282//bone mineralization;GO:0030335//positive regulation of cell migration;GO:0032815//negative regulation of natural killer cell activation;GO:0038096//Fc-gamma receptor signaling pathway involved in phagocytosis;GO:0043306//positive regulation of mast cell degranulation;GO:0043312//neutrophil degranulation;GO:0043552//positive regulation of phosphatidylinositol 3-kinase activity;GO:0045087//innate immune response;GO:0045088//regulation of innate immune response;GO:0045859//regulation of protein kinase activity;GO:0046777//protein autophosphorylation;GO:0048705//skeletal system morphogenesis;GO:0050764//regulation of phagocytosis;GO:0050830//defense response to Gram-positive bacterium
ENSG00000000971	1231	0.01	0.01	0	o	CFH	0.330185607747152	0.00332658488357103	0.0830671506514338	0.137792747747507	0.02379491307738	0	0.200717797580391	0.101698394953912	0.00606384571551997	0.224805016167561	0.0321814644634461	0	0.312553190524962	0.301416989097467	0	0	0	0	complement factor H [Source:HGNC Symbol;Acc:HGNC:4883]	Human Diseases;Organismal Systems	Infectious diseases;Immune system	ko05150//Staphylococcus aureus infection;ko04610//Complement and coagulation cascades	K04004;K04004	GO:0005576//extracellular region;GO:0005615//extracellular space;GO:0070062//extracellular exosome;GO:0072562//blood microparticle	GO:0005515//protein binding;GO:0008201//heparin binding;GO:0042802//identical protein binding;GO:0043395//heparan sulfate proteoglycan binding	GO:0002376//immune system process;GO:0006956//complement activation;GO:0006957//complement activation, alternative pathway;GO:0016032//viral process;GO:0030449//regulation of complement activation;GO:0045087//innate immune response;GO:1903659//regulation of complement-dependent cytotoxicity
ENSG00000001036	467	9.47	5.19	0	o	FUCA2	0.1996360539895	0.160349685980695	0.176261800893912	1.0653459165925	0.879515239207875	0.102043457022467	1.58315283120533	0.201771159278943	0.162984483091709	0.906656033491289	1.12835466480803	0.55674309072128	0.749024482798592	0.228122974722018	0.116250160524142	0.219448117254791	0.523064801405413	0.212395395267831	alpha-L-fucosidase 2 [Source:HGNC Symbol;Acc:HGNC:4008]	Cellular Processes;Metabolism	Transport and catabolism;Glycan biosynthesis and metabolism	ko04142//Lysosome;ko00511//Other glycan degradation	K01206;K01206	GO:0005576//extracellular region;GO:0005615//extracellular space;GO:0005764//lysosome;GO:0005788//endoplasmic reticulum lumen;GO:0035578//azurophil granule lumen;GO:0070062//extracellular exosome	GO:0004560//alpha-L-fucosidase activity;GO:0005515//protein binding;GO:0016787//hydrolase activity;GO:0016798//hydrolase activity, acting on glycosyl bonds	GO:0005975//carbohydrate metabolic process;GO:0006004//fucose metabolic process;GO:0008152//metabolic process;GO:0009617//response to bacterium;GO:0016139//glycoside catabolic process;GO:0043312//neutrophil degranulation;GO:0043687//post-translational protein modification;GO:0044267//cellular protein metabolic process;GO:2000535//regulation of entry of bacterium into host cell
ENSG00000001084	639	0.24	0.00	0	o	GCLC	0.154749025182831	0.143783819147452	0.167961117214334	0.579672902410175	0.162798632737619	0.153846975419384	0.0708109866361996	0.225175655066328	0.0951496542159141	0.36988732667404	0.30606662431205	0.149869502970473	0.536972778908918	0.154978049543154	0.118629630090604	0.0839168983779607	0.889495575036545	1.09937363575016	glutamate-cysteine ligase catalytic subunit [Source:HGNC Symbol;Acc:HGNC:4311]	Metabolism;Metabolism;Metabolism;Cellular Processes	Global and overview maps;Metabolism of other amino acids;Amino acid metabolism;Cell growth and death	ko01100//Metabolic pathways;ko00480//Glutathione metabolism;ko00270//Cysteine and methionine metabolism;ko04216//Ferroptosis	K11204;K11204;K11204;K11204	GO:0005739//mitochondrion;GO:0005829//cytosol;GO:0017109//glutamate-cysteine ligase complex	GO:0000166//nucleotide binding;GO:0000287//magnesium ion binding;GO:0003824//catalytic activity;GO:0004357//glutamate-cysteine ligase activity;GO:0005515//protein binding;GO:0005524//ATP binding;GO:0016595//glutamate binding;GO:0016874//ligase activity;GO:0043531//ADP binding;GO:0044877//protein-containing complex binding	GO:0006534//cysteine metabolic process;GO:0006536//glutamate metabolic process;GO:0006749//glutathione metabolic process;GO:0006750//glutathione biosynthetic process;GO:0006979//response to oxidative stress;GO:0007568//aging;GO:0007584//response to nutrient;GO:0009408//response to heat;GO:0009410//response to xenobiotic stimulus;GO:0009725//response to hormone;GO:0014823//response to activity;GO:0019852//L-ascorbic acid metabolic process;GO:0031397//negative regulation of protein ubiquitination;GO:0032436//positive regulation of proteasomal ubiquitin-dependent protein catabolic process;GO:0032869//cellular response to insulin stimulus;GO:0035729//cellular response to hepatocyte growth factor stimulus;GO:0043066//negative regulation of apoptotic process;GO:0043524//negative regulation of neuron apoptotic process;GO:0044344//cellular response to fibroblast growth factor stimulus;GO:0044752//response to human chorionic gonadotropin;GO:0045454//cell redox homeostasis;GO:0045892//negative regulation of transcription, DNA-templated;GO:0046685//response to arsenic-containing substance;GO:0046686//response to cadmium ion;GO:0051409//response to nitrosative stress;GO:0051900//regulation of mitochondrial depolarization;GO:0070555//response to interleukin-1;GO:0071260//cellular response to mechanical stimulus;GO:0071333//cellular response to glucose stimulus;GO:0071372//cellular response to follicle-stimulating hormone stimulus;GO:0097069//cellular response to thyroxine stimulus;GO:0097746//regulation of blood vessel diameter;GO:1901029//negative regulation of mitochondrial outer membrane permeabilization involved in apoptotic signaling pathway;GO:2000490//negative regulation of hepatic stellate cell activation;GO:2001237//negative regulation of extrinsic apoptotic signaling pathway
ENSG00000001167	347	0.47	0.00	0	o	NFYA	0.117359544053495	0.11038882268393	0.141721196527348	0.0971055525347844	0.0933559021179837	0.0937396836003206	0.115648589189751	0.105331146621955	0.166444406859744	0.227224657649346	0.0679428174389294	0.0463221980792287	0.127031208007691	0.163931876313321	0.120580201076582	0.0455504975574849	0.270080483984227	0	nuclear transcription factor Y subunit alpha [Source:HGNC Symbol;Acc:HGNC:7804]	Human Diseases;Human Diseases;Organismal Systems	Infectious diseases;Neurodegenerative disease;Immune system	ko05152//Tuberculosis;ko05017//Spinocerebellar ataxia;ko04612//Antigen processing and presentation	K08064;K08064;K08064	GO:0000785//chromatin;GO:0005634//nucleus;GO:0005654//nucleoplasm;GO:0016602//CCAAT-binding factor complex;GO:0032993//protein-DNA complex;GO:0090575//RNA polymerase II transcription factor complex	GO:0000976//transcription regulatory region sequence-specific DNA binding;GO:0000978//RNA polymerase II proximal promoter sequence-specific DNA binding;GO:0000981//DNA-binding transcription factor activity, RNA polymerase II-specific;GO:0003677//DNA binding;GO:0003700//DNA-binding transcription factor activity;GO:0005515//protein binding	GO:0006355//regulation of transcription, DNA-templated;GO:0006357//regulation of transcription by RNA polymerase II;GO:0006366//transcription by RNA polymerase II;GO:0019216//regulation of lipid metabolic process;GO:0045893//positive regulation of transcription, DNA-templated;GO:0048511//rhythmic process
ENSG00000001460	334	0.00	0.00	0	o	STPG1	0.0462633341288395	0.122712355752985	0.0477946331891091	0.0145821869224547	0.0198395549876934	0.0820702541367139	0.044648808793291	0.0393308193086425	0.110954492485922	0.175879630007826	0.047964365899838	0.0164500101172317	0.0678012068614821	0.0672130565071681	0.0833626546132889	0.122757668049723	0.108186470200037	1.12299963381962	sperm tail PG-rich repeat containing 1 [Source:HGNC Symbol;Acc:HGNC:28070]	-	-	-	-	GO:0005634//nucleus;GO:0005737//cytoplasm;GO:0005739//mitochondrion	GO:0003674//molecular_function	GO:0006915//apoptotic process;GO:0043065//positive regulation of apoptotic process;GO:1902110//positive regulation of mitochondrial membrane permeability involved in apoptotic process
ENSG00000001461	406	196.59	20.36	9	o34-53i75-97o102-121i134-156o171-193i202-224o239-261i274-296o301-320i	NIPAL3	0.447924565681104	0.670894689692038	0.553228343234544	0.088658986428545	0.0558208045118726	0.645255918674446	0.207483817980425	0.438873752256544	0.442111065866506	0.135937292250092	0.229863666276065	0.349678373489556	0.282025451365885	0.459067305718621	0.375919944001599	0.403869546539441	0.516808183132462	0.503973177775445	NIPA like domain containing 3 [Source:HGNC Symbol;Acc:HGNC:25233]	-	-	-	-	GO:0016020//membrane;GO:0016021//integral component of membrane	GO:0005515//protein binding;GO:0015095//magnesium ion transmembrane transporter activity	GO:0015693//magnesium ion transport;GO:1903830//magnesium ion transmembrane transport
ENSG00000001497	734	0.01	0.01	0	o	LAS1L	0.220497940240364	0.322984182806361	0.315227496541331	0.144841330961884	0.187226066285159	0.260518533278509	0.230013115333458	0.22093863858261	0.457119497356833	0.436485367302679	0.212853574263126	0.392765099882973	0.178006243153337	0.308392533942423	0.202664868796408	0.430746822852625	0	0.17526333315807	LAS1 like ribosome biogenesis factor [Source:HGNC Symbol;Acc:HGNC:25726]	-	-	-	-	GO:0005634//nucleus;GO:0005654//nucleoplasm;GO:0005730//nucleolus;GO:0005737//cytoplasm;GO:0016020//membrane;GO:0030687//preribosome, large subunit precursor;GO:0071339//MLL1 complex;GO:0090730//Las1 complex	GO:0003723//RNA binding;GO:0004519//endonuclease activity;GO:0005515//protein binding	GO:0000460//maturation of 5.8S rRNA;GO:0000470//maturation of LSU-rRNA;GO:0006364//rRNA processing;GO:0090305//nucleic acid phosphodiester bond hydrolysis
ENSG00000001561	453	21.65	0.02	1	o406-428i	ENPP4	0.22476363386287	0.0662689191743426	0.256930548552625	0.244221519852028	0.0994136110642092	0.0738149896364404	0.157972303423702	0.426375607032852	0.0483600517259508	0.428059947900829	0.0835734657731551	0.105221687037835	0.201336597313442	0.20735525966964	0.133947958880161	0.0440631680143388	0	0	ectonucleotide pyrophosphatase/phosphodiesterase 4 [Source:HGNC Symbol;Acc:HGNC:3359]	Metabolism;Metabolism	Global and overview maps;Nucleotide metabolism	ko01100//Metabolic pathways;ko00230//Purine metabolism	K18424;K18424	GO:0005886//plasma membrane;GO:0016020//membrane;GO:0016021//integral component of membrane;GO:0070062//extracellular exosome;GO:0101003//ficolin-1-rich granule membrane	GO:0003824//catalytic activity;GO:0005515//protein binding;GO:0016787//hydrolase activity;GO:0046872//metal ion binding;GO:0047710//bis(5'-adenosyl)-triphosphatase activity	GO:0007596//blood coagulation;GO:0007599//hemostasis;GO:0030194//positive regulation of blood coagulation;GO:0043312//neutrophil degranulation;GO:0046130//purine ribonucleoside catabolic process
ENSG00000001617	785	0.53	0.52	0	o	SEMA3F	0.00173231265471717	0	0.00177017217402633	2.85576556220885e-04	0.00638612884277665	0	0.00879826520630746	0	0	0.0930272970223032	0.00291328340835908	0	0	0	0	0	0	0	semaphorin 3F [Source:HGNC Symbol;Acc:HGNC:10728]	Organismal Systems	Development	ko04360//Axon guidance	K06840	GO:0005576//extracellular region;GO:0005615//extracellular space;GO:0005887//integral component of plasma membrane;GO:0098978//glutamatergic synapse	GO:0005515//protein binding;GO:0030215//semaphorin receptor binding;GO:0045499//chemorepellent activity	GO:0001755//neural crest cell migration;GO:0007411//axon guidance;GO:0021612//facial nerve structural organization;GO:0021637//trigeminal nerve structural organization;GO:0021675//nerve development;GO:0021785//branchiomotor neuron axon guidance;GO:0030335//positive regulation of cell migration;GO:0036486//ventral trunk neural crest cell migration;GO:0048843//negative regulation of axon extension involved in axon guidance;GO:0048846//axon extension involved in axon guidance;GO:0050919//negative chemotaxis;GO:0061549//sympathetic ganglion development;GO:0071526//semaphorin-plexin signaling pathway;GO:0097490//sympathetic neuron projection extension;GO:0097491//sympathetic neuron projection guidance;GO:0099175//regulation of postsynapse organization;GO:1901166//neural crest cell migration involved in autonomic nervous system development;GO:1902285//semaphorin-plexin signaling pathway involved in neuron projection guidance;GO:1902287//semaphorin-plexin signaling pathway involved in axon guidance
ENSG00000001626	1480	241.52	0.00	11	i84-106o121-143i196-215o219-241i304-326o859-881i901-923o986-1008i1015-1034o1098-1120i1129-1148o	CFTR	0	0	0	0	0	0	0.00121111947675636	0	0	0	0	0	0	0	0	0	0	0	CF transmembrane conductance regulator [Source:HGNC Symbol;Acc:HGNC:1884]	Environmental Information Processing;Cellular Processes;Environmental Information Processing;Organismal Systems;Organismal Systems;Organismal Systems;Human Diseases;Environmental Information Processing	Signal transduction;Cellular community - eukaryotes;Signal transduction;Digestive system;Digestive system;Digestive system;Infectious diseases;Membrane transport	ko04024//cAMP signaling pathway;ko04530//Tight junction;ko04152//AMPK signaling pathway;ko04972//Pancreatic secretion;ko04971//Gastric acid secretion;ko04976//Bile secretion;ko05110//Vibrio cholerae infection;ko02010//ABC transporters	K05031;K05031;K05031;K05031;K05031;K05031;K05031;K05031	GO:0005634//nucleus;GO:0005737//cytoplasm;GO:0005765//lysosomal membrane;GO:0005768//endosome;GO:0005769//early endosome;GO:0005783//endoplasmic reticulum;GO:0005789//endoplasmic reticulum membrane;GO:0005829//cytosol;GO:0005886//plasma membrane;GO:0005887//integral component of plasma membrane;GO:0009986//cell surface;GO:0010008//endosome membrane;GO:0016020//membrane;GO:0016021//integral component of membrane;GO:0016324//apical plasma membrane;GO:0030660//Golgi-associated vesicle membrane;GO:0030669//clathrin-coated endocytic vesicle membrane;GO:0031901//early endosome membrane;GO:0032991//protein-containing complex;GO:0034707//chloride channel complex;GO:0055037//recycling endosome;GO:0055038//recycling endosome membrane	GO:0000166//nucleotide binding;GO:0005254//chloride channel activity;GO:0005260//intracellularly ATP-gated chloride channel activity;GO:0005515//protein binding;GO:0005524//ATP binding;GO:0015106//bicarbonate transmembrane transporter activity;GO:0015108//chloride transmembrane transporter activity;GO:0016853//isomerase activity;GO:0016887//ATPase activity;GO:0019869//chloride channel inhibitor activity;GO:0019899//enzyme binding;GO:0030165//PDZ domain binding;GO:0042626//ATPase activity, coupled to transmembrane movement of substances;GO:0051087//chaperone binding;GO:0106138//Sec61 translocon complex binding	GO:0006695//cholesterol biosynthetic process;GO:0006811//ion transport;GO:0006821//chloride transport;GO:0006904//vesicle docking involved in exocytosis;GO:0015698//inorganic anion transport;GO:0015701//bicarbonate transport;GO:0016579//protein deubiquitination;GO:0030301//cholesterol transport;GO:0034220//ion transmembrane transport;GO:0034976//response to endoplasmic reticulum stress;GO:0035377//transepithelial water transport;GO:0035774//positive regulation of insulin secretion involved in cellular response to glucose stimulus;GO:0035973//aggrephagy;GO:0045921//positive regulation of exocytosis;GO:0048240//sperm capacitation;GO:0050891//multicellular organismal water homeostasis;GO:0051454//intracellular pH elevation;GO:0055085//transmembrane transport;GO:0060081//membrane hyperpolarization;GO:0061024//membrane organization;GO:0071320//cellular response to cAMP;GO:1902161//positive regulation of cyclic nucleotide-gated ion channel activity;GO:1902476//chloride transmembrane transport;GO:1902943//positive regulation of voltage-gated chloride channel activity;GO:1904322//cellular response to forskolin
ENSG00000001629	1089	0.02	0.00	0	o	ANKIB1	0.343265811478282	0.547645027969073	0.548643633973507	0.341469024180592	0.297144935905208	0.502570627097508	0.48168538853048	0.416666977234865	0.435941318168626	0.681877125260961	0.228418912301111	0.481893147719602	0.205710336366754	0.634397335006283	0.165812098809473	0.529642254542293	0.158075275446167	0.4721110932069	ankyrin repeat and IBR domain containing 1 [Source:HGNC Symbol;Acc:HGNC:22215]	-	-	-	-	GO:0000151//ubiquitin ligase complex;GO:0005737//cytoplasm	GO:0004842//ubiquitin-protein transferase activity;GO:0005515//protein binding;GO:0016740//transferase activity;GO:0031624//ubiquitin conjugating enzyme binding;GO:0046872//metal ion binding;GO:0061630//ubiquitin protein ligase activity	GO:0000209//protein polyubiquitination;GO:0006511//ubiquitin-dependent protein catabolic process;GO:0016567//protein ubiquitination;GO:0032436//positive regulation of proteasomal ubiquitin-dependent protein catabolic process
ENSG00000001630	509	40.07	33.71	2	o4-21i28-50o	CYP51A1	0.0114221529903086	0.035261288744084	0.0173815045670759	0.0507115075198771	0.055111173852182	0.0222415496100196	0.118927886580484	0.038927278087485	0.0755169402778459	0.1482857401433	0.0484280839581575	0.00739805298041661	0.228611036152519	0.00696097676425956	0.0947723634130964	0.126792348377981	0	0.208938384070538	cytochrome P450 family 51 subfamily A member 1 [Source:HGNC Symbol;Acc:HGNC:2649]	Metabolism;Metabolism	Global and overview maps;Lipid metabolism	ko01100//Metabolic pathways;ko00100//Steroid biosynthesis	K05917;K05917	GO:0005783//endoplasmic reticulum;GO:0005789//endoplasmic reticulum membrane;GO:0016020//membrane;GO:0016021//integral component of membrane;GO:0043231//intracellular membrane-bounded organelle	GO:0004497//monooxygenase activity;GO:0005506//iron ion binding;GO:0008398//sterol 14-demethylase activity;GO:0016491//oxidoreductase activity;GO:0016705//oxidoreductase activity, acting on paired donors, with incorporation or reduction of molecular oxygen;GO:0020037//heme binding;GO:0046872//metal ion binding	GO:0006629//lipid metabolic process;GO:0006694//steroid biosynthetic process;GO:0006695//cholesterol biosynthetic process;GO:0007399//nervous system development;GO:0008202//steroid metabolic process;GO:0008203//cholesterol metabolic process;GO:0016125//sterol metabolic process;GO:0016126//sterol biosynthetic process;GO:0019216//regulation of lipid metabolic process;GO:0033488//cholesterol biosynthetic process via 24,25-dihydrolanosterol;GO:0042177//negative regulation of protein catabolic process;GO:0050709//negative regulation of protein secretion;GO:0055114//oxidation-reduction process;GO:0070988//demethylation;GO:1900222//negative regulation of amyloid-beta clearance
ENSG00000001631	736	0.12	0.00	0	o	KRIT1	0.213928481114548	0.262328784182478	0.266191503138446	0.102019344775383	0.098969734980181	0.228862293486802	0.164201016541206	0.230003707961967	0.181494489017314	0.221743830056701	0.082807660261042	0.175568121013173	0.133357312651601	0.262981920399144	0.294681065085387	0.10789270557442	0.612357804544875	0.208938384070538	KRIT1 ankyrin repeat containing [Source:HGNC Symbol;Acc:HGNC:1573]	Environmental Information Processing	Signal transduction	ko04015//Rap1 signaling pathway	K17705	GO:0005615//extracellular space;GO:0005737//cytoplasm;GO:0005856//cytoskeleton;GO:0005886//plasma membrane;GO:0005911//cell-cell junction;GO:0016020//membrane;GO:0030054//cell junction	GO:0005515//protein binding;GO:0005546//phosphatidylinositol-4,5-bisphosphate binding;GO:0008017//microtubule binding;GO:0030695//GTPase regulator activity	GO:0001525//angiogenesis;GO:0001937//negative regulation of endothelial cell proliferation;GO:0007264//small GTPase mediated signal transduction;GO:0010596//negative regulation of endothelial cell migration;GO:0016525//negative regulation of angiogenesis;GO:0045454//cell redox homeostasis;GO:0050790//regulation of catalytic activity;GO:2000114//regulation of establishment of cell polarity;GO:2000352//negative regulation of endothelial cell apoptotic process
ENSG00000002016	418	0.00	0.00	0	o	RAD52	0.0397835964914088	0.03717003865096	0.0309314482222248	0.0176457448656085	0.0151602795477582	0.0377547204112302	0.0322419975716138	0.0269728835061434	0.0377499089854786	0.0538850712694102	0.0252003492861162	0	0.0622200099552016	0.0272116804762136	0.0109970457383705	0.0323501057848459	0.183432386822217	0	RAD52 homolog, DNA repair protein [Source:HGNC Symbol;Acc:HGNC:9824]	Genetic Information Processing	Replication and repair	ko03440//Homologous recombination	K10873	GO:0005634//nucleus;GO:0005654//nucleoplasm;GO:0032991//protein-containing complex;GO:0032993//protein-DNA complex	GO:0003677//DNA binding;GO:0003697//single-stranded DNA binding;GO:0005515//protein binding;GO:0042802//identical protein binding	GO:0000724//double-strand break repair via homologous recombination;GO:0000730//DNA recombinase assembly;GO:0006281//DNA repair;GO:0006302//double-strand break repair;GO:0006310//DNA recombination;GO:0006312//mitotic recombination;GO:0006974//cellular response to DNA damage stimulus;GO:0010792//DNA double-strand break processing involved in repair via single-strand annealing;GO:0034599//cellular response to oxidative stress;GO:0045002//double-strand break repair via single-strand annealing;GO:2000819//regulation of nucleotide-excision repair

9 细胞周期分析

9.1 细胞周期评估

常规样本中，仅干细胞、祖细胞、癌细胞等具备增殖分化潜力的细胞才具有细胞分裂的能力，即处于细胞周期中。我们通过周期蛋白在细胞中的表达情况对细胞所处的细胞周期进行评分，以此直观体现各个样本中的细胞分裂/增殖活性。

Fig 9-1-1 不同样本的细胞周期指数评估

9.2 细胞周期推断

每一个细胞周期都有特征表达的周期蛋白，通过每个细胞周期的特征周期蛋白^[21]，我们可以对细胞的各个细胞周期进行评分，通过评分，我们可以推测细胞所处的细胞周期：

• 我们可以推测细胞所处的细胞周期细胞在所有细胞周期中的评分均<0，则认为细胞不处于细胞周期中
• 细胞获得最高分值所对应的细胞周期被认为是细胞所处细胞周期

Tab 9-2-1 各细胞的细胞周期表

Cells	Samples	Clusters	G1	S	G2	M	CellCycle.Score	Phase
AdjacNormal_AAACCCAAGAAGATCT	AdjacNormal	1	0.0116144488108683	-0.0424193077599221	-0.0660583741165098	-0.0263608356346551	0.0116144488108683	G1
AdjacNormal_AAACCCAAGACTCGAG	AdjacNormal	5	-0.0434439808370012	0.0481355966792152	-0.0273299069290547	0.0187691759532517	0.0481355966792152	S
AdjacNormal_AAACCCACACTGGATT	AdjacNormal	5	-0.0404035085419784	-0.0850922468073793	0.0305228485059817	0.00252462744686152	0.0305228485059817	G2
AdjacNormal_AAACCCACAGAGGCTA	AdjacNormal	2	0.0716072804220174	0.035950941110335	0.0128345509623975	0.0359651948819074	0.0716072804220174	G1
AdjacNormal_AAACCCAGTTTGTTCT	AdjacNormal	14	-0.100669333403082	-0.0797571949551742	-0.0218257307389038	-0.0318318186320522	-0.0218257307389038	non-cycling
AdjacNormal_AAACCCATCGGAAGGT	AdjacNormal	6	-0.184635854661247	-0.216029363283324	-0.10688898571373	-0.0777946857335721	-0.0777946857335721	non-cycling
AdjacNormal_AAACGAAAGAGGATCC	AdjacNormal	3	-0.0417624993915903	-0.0333476092557671	-0.0725326456513034	-0.100543559462892	-0.0333476092557671	non-cycling
AdjacNormal_AAACGAAAGCACTCCG	AdjacNormal	0	0.0497452242565037	0.0288078982973114	-0.0564401978253098	-0.0360705487412817	0.0497452242565037	G1
AdjacNormal_AAACGAACAGTAGATA	AdjacNormal	1	-0.0871507663884806	0.0299758126369763	-0.0599967580361364	-0.0658887679115304	0.0299758126369763	S
AdjacNormal_AAACGAAGTAATGCGG	AdjacNormal	4	-0.11012409998223	-0.0635441153308885	0.045948737361201	0.0492754353277924	0.0492754353277924	M
AdjacNormal_AAACGAAGTATCCTTT	AdjacNormal	0	-0.192176473881201	0.019461554177533	-0.116390747271062	-0.116241765984339	0.019461554177533	S
AdjacNormal_AAACGAAGTGGCCACT	AdjacNormal	4	-0.153908798913884	-0.0971036266040841	-0.104308154803936	0.00104603279222987	0.00104603279222987	M
AdjacNormal_AAACGAAGTTGGCTAT	AdjacNormal	0	-0.0172322426095888	0.0149150085341538	0.0293337504152403	-0.100170603754287	0.0293337504152403	G2
AdjacNormal_AAACGAAGTTTAGTCG	AdjacNormal	5	-0.0567825855829962	-0.0753566120962961	-0.0833774827833383	-0.123560252018268	-0.0567825855829962	non-cycling
AdjacNormal_AAACGAATCGCATAGT	AdjacNormal	0	-0.0916990623077417	-0.0827937719545597	0.00231204752637706	-0.0794240895451596	0.00231204752637706	G2
AdjacNormal_AAACGCTAGAATCTAG	AdjacNormal	7	-0.109148004867408	-0.0803670224961999	-0.00986313780847131	-0.163963734957107	-0.00986313780847131	non-cycling
AdjacNormal_AAACGCTAGAGATCGC	AdjacNormal	6	-0.114586948428964	-0.204654822111741	-0.0441475728652551	-0.138470617729536	-0.0441475728652551	non-cycling
AdjacNormal_AAACGCTAGATGCGAC	AdjacNormal	2	-0.133572387513075	-0.0413708063962026	-0.0546673545839012	-0.0684203654998439	-0.0413708063962026	non-cycling
AdjacNormal_AAACGCTAGGAACATT	AdjacNormal	0	-0.0622745380266054	-0.0561355663282031	-0.0170165641130481	-0.0205165586392129	-0.0170165641130481	non-cycling
AdjacNormal_AAACGCTAGGTTACCT	AdjacNormal	5	-0.0869790377817816	0.148230255908973	-0.0175133530884733	-0.0871933883387812	0.148230255908973	S

Fig 9-2-1 不同样本的不同细胞周期细胞的数量堆叠图		Fig 9-2-2 不同样本的不同细胞周期细胞的数量比例堆叠图

Fig 9-2-3 不同细胞周期细胞的tSNE分布

Fig 9-2-4 Seurat分群与细胞周期推断对应circos图

9.3 周期蛋白基因分布可视化

细胞周期推断是基于每个细胞周期的特征周期蛋白基因在细胞中的表达量，利用软件预测的结果。那么我们就可以通过观察细胞周期特征基因的表达分布，对预测结果进行初步验证，这个过程即为周期蛋白基因分布可视化。

周期蛋白基因：CellCycle.genes.xls

热图可以同时展示大量基因在每个细胞中的表达量及其在细胞群体中的分布情况。使用热图展示周期蛋白基因在不同细胞周期的表达量，可以看到各时期特征蛋白基因相对集中表达在对应的时期中，是对细胞周期推断结果准确性的验证。

Fig 9-3-1 周期蛋白基因在不同细胞周期的表达量热图

广州基迪奥生物科技有限公司

10 个性化分析推荐

10.1 细胞亚群鉴定

10.2 拟时分析

10.3 细胞周期分析

10.4 WGCNA

10.5 转录因子分析

10.6 细胞通讯分析

广州基迪奥生物科技有限公司

11 目录结构

结果文件夹
├── 1.Expression                                            定量结果文件夹
│   ├── barcode_plot                                            有效细胞鉴定图文件夹
│   │   └── *.barcode_plot.{pdf,png}                                有效细胞鉴定图
│   ├── CellRanger_Report                                       Cell Ranger报告文件夹
│   │   └── CellRanger.*.result.html                                Cell Ranger count结果报告
│   ├── expressions                                             表达量结果文件夹
│   │   ├── *                                                       各样本结果文件夹
│   │   │   ├── expression.xls                                          表达量矩阵表
│   │   │   ├── barcodes.tsv                                            细胞barcode ID表
│   │   │   ├── genes.tsv                                               基因ID与名称表
│   │   │   └── matrix.mtx                                              表达量稀疏矩阵
│   │   └── *.expression.demo.xls                                   表达量矩阵示例表
│   ├── samples.align.stat.xls                                  各样本比对结果统计表
│   └── samples.sequence.stat.xls                               各样本测序数据统计表
├── 2.Cluster                                               聚类结果文件夹
│   ├── 1.QC                                                    质控结果文件夹
│   │   ├── AfterFilter.BasicInfo.merge.{pdf,png}                   过滤后各个样本细胞基本信息的分布图
│   │   ├── AfterFilter.BasicInfo.nUMI-nGene.{pdf,png}              过滤后各个样本细胞基本信息的分布散点图
│   │   ├── AfterFilter.BasicInfo.nUMI-pMito.{pdf,png}              过滤后各个样本细胞基本信息的分布散点图
│   │   ├── AfterFilter.BasicInfo.PresetMarker.{pdf,png}            过滤后各个样本细胞中预设标记基因的表达量分布
│   │   ├── BasicInfo.merge.{pdf,png}                               过滤前各个样本细胞基本信息的分布图
│   │   ├── BasicInfo.nUMI-nGene.{pdf,png}                          过滤前各个样本细胞基本信息的分布散点图
│   │   ├── BasicInfo.nUMI-pMito.{pdf,png}                          过滤前各个样本细胞基本信息的分布散点图
│   │   ├── BasicInfo.PresetMarker.{pdf,png}                        过滤前各个样本细胞中预设标记基因的表达量分布
│   │   └── Filter.stat.xls                                         过滤前后各个样本中细胞数据量统计表
│   ├── 2.cluster                                               分群结果文件夹
│   │   ├── AllGene.avg_exp.annot.xls                               基因在各个亚群中表达量的均值表
│   │   ├── Cells.cluster.list.xls                                  细胞与亚群对照表
│   │   ├── tSNE_*.{pdf,png}                                        各样本单细胞亚群分类tSNE图
│   │   └── tSNE.{pdf,png}                                          单细胞亚群分类tSNE图
│   ├── 3.cluster_stat                                          分群结果的统计结果文件夹
│   │   ├── Cluster.stat.inSamples.pct.{pdf,png}                    各亚群中各个样本细胞数量百分比堆叠图
│   │   ├── Cluster.stat.inSamples.{pdf,png}                        各亚群中各个样本细胞数量堆叠图
│   │   ├── Cluster.stat.bySamples.pct.{pdf,png}                    各样本中各亚群细胞数量百分比堆叠图
│   │   ├── Cluster.stat.bySamples.{pdf,png}                        各样本中各亚群细胞数量堆叠图
│   │   ├── Cluster.stat.Sample.xls                                 各样本中各亚群细胞数量统计表
│   │   ├── Cluster.stat.xls                                        细胞亚群分类结果统计表
│   │   ├── Cluster.cor.heatmap.{pdf,png}                           各亚群相关性系数热图
│   │   ├── PresetMarker.Distribution.{pdf,png}                     已知标记基因在各个细胞亚群中的表达分布
│   │   ├── PresetMarker.DotPlot.{pdf,png}                          已知标记基因在各个细胞亚群中的表达分布气泡图
│   │   ├── PresetMarker.Heatmap.{pdf,png}                          已知标记基因在各个亚群的表达量热图
│   │   └── PresetMarker.VlnPlot.{pdf,png}                          已知标记基因在各个细胞亚群中的表达分布小提琴图
│   └── 4.CellAnnotation                                        单细胞亚群鉴定结果文件夹
│       ├── Cell.annotation.stat.xls                                各样本在各个细胞类型中细胞数量统计表
│       ├── Cells.annotation.circos.{pdf,png}                       Seurat分群与singleR细胞鉴定对应circos图
│       ├── Cells.annotation.{pdf,png}                              各细胞类型在tSNE图的分布
│       ├── Cluster.correlation.heatmap.{pdf,png}                   Seurat分群与singleR鉴定细胞类型相关性热图
│       ├── Cluster.sample.singleR.stat.pct.{pdf,png}               各细胞类型中各样本细胞数量百分比堆叠图
│       ├── Cluster.sample.singleR.stat.{pdf,png}                   各细胞类型中各样本细胞数量堆叠图
│       ├── Cluster.stat.sample.singleR.xls                         各样本在各个细胞类型中细胞数量统计表
│       ├── Sample.cluster.singleR.stat.pct.{pdf,png}               各样本中各细胞类型数量百分比堆叠图
│       └── Sample.cluster.singleR.stat.{pdf,png}                   各样本中各细胞类型数量堆叠图
├── 3.MarkerGene                                            亚群上调表达基因分析结果文件夹
│   ├── DeGene.list.xls                                         各亚群差异基因注释表
│   ├── DeGene.stat.{pdf,png}                                   各亚群上调基因数量统计柱状图
│   ├── DeGene.stat.xls                                         各亚群上调基因数量统计表
│   ├── Enrichment                                              上调表达基因富集分析结果文件夹
│   │   ├── GO                                                      GO功能富集分析结果文件夹
│   │   ├── KO                                                      KO功能富集分析结果文件夹
│   │   ├── DO                                                      DO功能富集分析结果文件夹
│   │   └── Reactome                                                Reactome功能富集分析结果文件夹
│   ├── Plots                                                   上调基因表达分布结果文件夹
│   │   ├── Top.DotPlot.{pdf,png}                                   标记基因表达分布气泡图
│   │   ├── Top.Heatmap.{pdf,png}                                   标记基因表达热图
│   │   ├── ExpPlot                                                 标记基因表达分布图文件夹
│   │   ├── DensityPlot                                             标记基因表达分布密度图文件夹
│   │   └── ViolinPlot                                              标记基因表达分布小提琴图文件夹
│   └── String                                                  蛋白质互作网络分析结果文件夹
│       ├── Top.aln.links.xls                                       标记基因与String蛋白对应表及析构关系表
│       ├── Top.edge.tsv                                            Cytoscape绘图文件--连接信息文件
│       └── Top.node.tsv                                            Cytoscape绘图文件--节点信息文件
├── 4.GSVA                                                  GSVA分析
│   ├── *.gsva.xls                                              各细胞富集程度表
│   └── *.heatmap.cluster.{xls,pdf,png}                         各个亚群中的富集分数热图
├── 5.TF                                                    转录因子注释结果文件夹
│   └── TF.annot.xls                                            转录因子注释表
├── 6.CellCycle                                             细胞周期分析
│   ├── CellCycle.annot.xls                                     各细胞的细胞周期表
│   ├── CellCycle.boxplot.{pdf,png}                             不同样本的细胞周期指数评估盒形图
│   ├── CellCycle.DotPlot.{pdf,png}                             周期蛋白基因的分布气泡图
│   ├── CellCycle.Heatmap.{pdf,png}                             周期蛋白基因在不同细胞周期的表达量热图
│   ├── Phase.stat.bySamples.pct.{pdf,png}                      不同样本的不同细胞周期细胞的数量比例堆叠图
│   ├── Phase.stat.bySamples.{pdf,png}                          不同样本的不同细胞周期细胞的数量堆叠图
│   ├── CellCycle.Cluster.tSNE.{pdf,png}                        不同细胞周期细胞与分群的tSNE分布
│   └── CellCycle.Samples.tSNE.{pdf,png}                        不同细胞周期细胞与样本的tSNE分布
├── 7.RNAVelocity                                           RNA速率分析
│   ├── velocity.trajectory.tSNE.{pdf,png}                      RNA速率轨迹图
│   └── velocity.tSNE.{pdf,png}                                 RNA速率分布图
├── index.html                                              单细胞分析结果网页版报告
├── scRNA-seq_method.pdf                                    单细胞分析方法说明（英文版）
└── src                                                     网页版报告系统文件文件夹

广州基迪奥生物科技有限公司

12 参考文献

• [1] cellranger : http://support.10xgenomics.com/single-cell/software/overview/welcome
• [2] Butler A, Hoffman P, Smibert P, et al. Integrating single-cell transcriptomic data across different conditions, technologies, and species. Nat Biotechnol. 2018;36(5):411-420.
• [3] Stuart T, Butler A, Hoffman P, et al. Comprehensive Integration of Single-Cell Data. Cell. 2019;177(7):1888-1902.e21.
• [4] van der Maaten Laurens and Hinton Geoffrey. Visualizing data using t-SNE. Journal of Machine Learning Research. 2008;9(November):2579–2605.
• [5] Aran D, Looney AP, Liu L, et al. Reference-based analysis of lung single-cell sequencing reveals a transitional profibrotic macrophage. Nat Immunol. 2019;20(2):163-172.
• [6] Ashburner M, Ball CA, Blake JA, et al. Gene ontology: tool for the unification of biology. The Gene Ontology Consortium. Nat Genetics, 2000;25(1):25-29.
• [7] Kanehisa M, Goto S. KEGG: kyoto encyclopedia of genes and genomes. Nucleic Acids Res, 2000;28(1):27-30.
• [8] Fabregat A, Jupe S, Matthews L, et al. The Reactome Pathway Knowledgebase. Nucleic Acids Res. 2018;46(D1):D649-D655. doi:10.1093/nar/gkx1132
• [9] Schriml LM, Mitraka E, Munro J, et al. Human Disease Ontology 2018 update: classification, content and workflow expansion. Nucleic Acids Res. 2019;47(D1):D955-D962.
• [10] Franceschini A, Szklarczyk D, Frankild S, et al. STRING v9.1: protein-protein interaction networks, with increased coverage and integration. Nucleic Acids Res. 2013;41(Database issue):D808-D815.
• [11] Hänzelmann S, Castelo R, Guinney J. GSVA: gene set variation analysis for microarray and RNA-seq data. BMC Bioinformatics. 2013;14:7.
• [12] Liberzon A, Birger C, Thorvaldsdóttir H, Ghandi M, Mesirov JP, Tamayo P. The Molecular Signatures Database (MSigDB) hallmark gene set collection. Cell Syst. 2015;1(6):417-425.
• [13] Weijun Liu and Xiaowei Wang. Prediction of functional microRNA targets by integrative modeling of microRNA binding and target expression data. Genome Biology. 2019; 20(1):18.
• [14] Yuhao Chen and Xiaowei Wang. miRDB: an online database for prediction of functional microRNA targets. Nucleic Acids Research. 2020;48(D1):D127-D131.
• [15] Griffiths-Jones S, Grocock RJ, van Dongen S, Bateman A, Enright AJ. miRBase: microRNA sequences, targets and gene nomenclature. Nucleic Acids Res. 2006;34(Database issue):D140-D144.
• [16] Yevshin I, Sharipov R, Kolmykov S, Kondrakhin Y, Kolpakov F. GTRD: a database on gene transcription regulation-2019 update. Nucleic Acids Res. 2019;47(D1):D100-D105.
• [17] Xie X, Lu J, Kulbokas EJ, et al. Systematic discovery of regulatory motifs in human promoters and 3' UTRs by comparison of several mammals. Nature. 2005;434(7031):338-345.
• [18] Subramanian A, Tamayo P, Mootha VK, et al. Gene set enrichment analysis: a knowledge-based approach for interpreting genome-wide expression profiles. Proc Natl Acad Sci U S A. 2005;102(43):15545-15550.
• [19] Segal E, Friedman N, Koller D, Regev A. A module map showing conditional activity of expression modules in cancer. Nat Genet. 2004;36(10):1090-1098.
• [20] Godec J, Tan Y, Liberzon A, et al. Compendium of Immune Signatures Identifies Conserved and Species-Specific Biology in Response to Inflammation. Immunity. 2016;44(1):194-206.
• [21] Macosko EZ, Basu A, Satija R, et al. Highly Parallel Genome-wide Expression Profiling of Individual Cells Using Nanoliter Droplets. Cell. 2015;161(5):1202-1214.

广州基迪奥生物科技有限公司

13 附录

13.1 分析方法英文文档

13.2 结果文件查看

13.3 文章引用与致谢

• Method部分：The cDNA/DNA/Small RNA libraries were sequenced on the Illumina sequencing platform by Genedenovo Biotechnology Co., Ltd (Guangzhou, China).
• Acknowledgements部分：We are grateful to/thank Guangzhou Genedenovo Biotechnology Co., Ltd for assisting in sequencing and/or bioinformatics analysis.

广州基迪奥生物科技有限公司