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一文解锁机制研究神器——IPA分析！
今天，我们一起看看IPA分析如何从组学数据中轻松get机制研究？
RNA-seq机制研究套餐采用了更高级的生信分析数据库Ingenuity Pathway Analysis（IPA）来对测序数据进行分析，IPA所基于的后台是一个高度结构化的ingenuity knowledge base数据库，并且它是一个收费数据库，每年的账号使用费数十万，该数据库经历20年的海量知识数据投入，号称拥有近500名PhD对近700多种权威杂志进行全文阅读，3000多种杂志进行摘要阅读，保存每周更新一次。目前数据库存储了530万条以上的生物实验发现，150万条互作信息和3万种以上的分子信息；此外，还构建了完整的功能疾病分类数据库，绘制了800种以上的信号通路，代谢通路等，为广大科研工作者提供及时、准确的生物信息学数据支持。
吉凯基因IPA分析主要包含5个模块
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一、经典通路分析
（ 寻找目的基因调控以后显著影响的信号通路）
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二、上游调控分析
（寻找差异基因上游关键调控因子）
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三、疾病和功能分析
（寻找差异基因主要影响的疾病功能方向）
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四、调控效应分析
（寻找上游因子、差异基因、下游功能之间的可能作用途径）
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五、互作网路分析
（寻找某一功能方向相关差异分子之间的互作关系）
应用案例
案例一
技术路线：
01
细胞基因操+RNA-seq
02
IPA分析
03
Q-PCR验证
总结：为了探索生长蛋白4抑制剂（ING4）在前列腺癌（PC）中的作用机制，在LNCaP细胞中，敲低ING4后进行了RNA-Seq，利用IPA网络分析模块，分析了差异基因的重要调控网络，第一次从整个基因调控的层面展示了ING4对PC细胞的调控作用。
案例二
技术路线：
01
外周血单核细胞（PBMC)+RNA-seq
02
IPA分析
03
Q-PCR验证
总结：为了研究长期暴露于砷污染饮用水个体的基因表达变化；将29名受试者外周血单核细胞（PBMC）中提取的RNA进行RNA-seq检测，IPA分析发现：总共1,054个基因与尿砷水平的升高显着相关其并且发现了潜在的靶基因（DAPK1，EGR2，APP），microRNA（miR-155，-338，-210）以及与砷致癌相关的途径（NOTCH信号途径）。
案例三
技术路线：
总结：该研究通过RNA-seq+IPA高级生信分析承上启下，发现了TRIM24是GLUT4的主要下游调节子；证实DDX58是TRIM24的下游靶标，提示：GLUT4促进头颈部鳞状细胞癌转移可能是通过TRIM24-DDX58轴实现的。
案例四
技术路线：
总结：该研究通过RNA-seq+IPA高级生信分析承上启下，发现了RAB3C促进结直肠癌发生发展的作用机制可能是通过调控IL-6来实现的。
RNA-seq+IPA分析应用文献集锦
1.Reperfusion-triggered stress protein response in the myocardium is blocked by post-conditioning. Systems biology pathway analysis highlights the key role of the canonical aryl-hydrocarbon receptor pathway IF=23.239
2.Low-Molecular-Weight Protein Tyrosine Phosphatase Predicts Prostate Cancer Outcome by Increasing the Metastatic Potential IF=17.298
3. Global gene expression profiling in mouse plasma cell tumor precursor and bystander cells reveals potential intervention targets for plasma cell neoplasia IF=16.562
4. The pruritus- and TH2-associated cytokine IL-31 promotes growth of sensory nerves IF=14.11
5.Use of contraceptive depot medroxyprogesterone acetate is associated with impaired cervicovaginal mucosal integrity IF=12.28
6. Kidney-targeted inhibition of protein kinase C-a ameliorates nephrotoxic nephritis with restoration of mitochondrial dysfunction IF=8.306
7. LncRNA MIR31HG targets HIF1A and P21 to facilitate head and neck cancer cell proliferation and tumorigenesis by promoting cell-cycle progression IF=10.698
8. Secretory RAB GTPase 3C modulates IL6-STAT3 pathway to promote colon cancer metastasis and is associated with poor prognosis IF=10.698
9. Phosphorylation of αB-crystallin supports reactive astrogliosis in demyelination IF=9.58
10.In Vivo Therapeutic Success of MicroRNA-155 Antagomir in a Mouse Model of Lupus Alveolar Hemorrhage IF=9.02
11. An FGFR3 autocrine loop sustains acquired resistance to trastuzumab in gastric cancer patients IF=8.91
12.Glucose transporter 4 promotes head and neck squamous cell carcinoma metastasis through the TRIM24-DDX58 axis IF=8.731
13. Epigenetic modification of microRNA-200b contributes to diabetic vasculopathy IF=8.402
14.Identification of transcriptome signature for myocardial reductive stress IF=7.79
15.Transcriptomic and Functional Analyses on the Effects of Dioxin on Insulin Secretion of Pancreatic Islets and #-cells IF=7.14
16. Human airway epithelial extracellular vesicle miRNA signature is altered upon asthma development IF=6.77
17.Essential role of JunD in cell proliferation is mediated via MYC signaling in prostate cancer cells IF=6.5
18.Poly(ADP-ribose) polymerase 1 is necessary for coactivating hypoxia-inducible factor-1- dependent gene expression by Epstein-Barr virus latent membrane protein 1 IF=6.46
19. RGS4 maintains chronic pain symptoms in rodent models IF=6.07
20.PUM1 knockdown prevents tumor progression by activating the PERK/eIF2/ ATF4 signaling pathway in pancreatic adenocarcinoma cells IF=5.95
21. Lamin A/C negatively regulated by miR‐124‐3p modulates apoptosis of vascular smooth muscle cells during cyclic stretch application in rats IF=5.86
22.PBMC gene expression profiles of female Bangladeshi adults chronically exposed to arsenic-contaminated drinking water IF=5.714
23.Gene Expression Profiling of NFATc1-Knockdown in RAW 264.7 Cells: An Alternative Pathway for Macrophage Differentiation IF=5.656
24.Differential Regulation of TLE3 in Sertoli Cells of the Testes during Postnatal Development IF=5.656
25.Matcha green tea (MGT) inhibits the propagation of cancer stem cells (CSCs), by targeting mitochondrial metabolism, glycolysis and multiple cell signalling pathways IF=5.515
26.Long-term exercise prevents hepatic steatosis: a novel role of FABP1 in regulation of autophagy-lysosomal machinery IF=5.39
27.Lysozyme-Induced Transcriptional Regulation of TNF-α Pathway Genes in Cells of the Monocyte Lineage IF=4.18
28.Moringa Isothiocyanate Activates Nrf2: Potential Role in Diabetic Nephropathy IF=3.545
29.IL-1-conferred gene expression pattern in ERα+ BCa and AR+ PCa cells is intrinsic to ERα− BCa and AR− PCa cells and promotes cell survival IF=2.933
30.Identification of the inhibitor of growth protein 4 (ING4) as a potential target in prostate cancer therapy IF=2.884
1.实验技术干货
2.蛋白质组学研究
3.腺病毒简介及应用
6.单细胞测序
8.悬浮细胞专用病毒
10.测序技术研究与应用
12.腺相关病毒选择/应用
13.表观遗传研究
14.文章解析
15.国自然课题设计思路解析
16.生物信息分析及工具
17.外泌体研究
18.肿瘤免疫研究
19.高分文章
