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chromMAGMA：基于调控元件的风险变异体分析。

chromMAGMA: regulatory element-centric interrogation of risk variants.

机构信息

Women's Cancer Research Program at the Samuel Oschin Comprehensive Cancer Center, Cedars-Sinai Medical Center, Los Angeles, CA, USA.

Division of Gynecologic Oncology, Department of Obstetrics and Gynecology, Cedars-Sinai Medical Center, Los Angeles, CA, USA.

出版信息

Life Sci Alliance. 2022 Jul 1;5(10). doi: 10.26508/lsa.202201446. Print 2022 Oct.

DOI:10.26508/lsa.202201446
PMID:35777959
原文链接:https://pmc.ncbi.nlm.nih.gov/articles/PMC9251535/
Abstract

Candidate causal risk variants from genome-wide association studies reside almost exclusively in noncoding regions of the genome and innovative approaches are necessary to understand their biological function. Multi-marker analysis of genomic annotation (MAGMA) is a widely used program that nominates candidate risk genes by mapping single-nucleotide polymorphism summary statistics from genome-wide association studies to gene bodies. We augmented MAGMA to create chromatin-MAGMA (chromMAGMA), a method to nominate candidate risk genes based on the presence of risk variants within noncoding regulatory elements (REs). We applied chromMAGMA to a genetic susceptibility dataset for epithelial ovarian cancer (EOC), a rare gynecologic malignancy characterized by high mortality. This identified 155 unique candidate EOC risk genes across five EOC histotypes; 83% (105/127) of high-grade serous ovarian cancer risk genes had not previously been implicated in this EOC histotype. Risk genes nominated by chromMAGMA converged on mRNA splicing and transcriptional dysregulation pathways. chromMAGMA is a pipeline that nominates candidate risk genes through a gene regulation-focused approach and helps interpret the biological mechanism of noncoding risk variants for complex diseases.

摘要

候选因果风险变异来自全基因组关联研究，几乎完全位于基因组的非编码区域，因此需要创新的方法来了解它们的生物学功能。全基因组关联研究中多标记分析基因组注释（MAGMA）是一种广泛使用的程序，通过将单核苷酸多态性汇总统计数据从全基因组关联研究映射到基因体来提名候选风险基因。我们扩展了 MAGMA 以创建染色质-MAGMA（chromMAGMA），这是一种基于非编码调控元件（REs）内存在风险变异来提名候选风险基因的方法。我们将 chromMAGMA 应用于上皮性卵巢癌（EOC）的遗传易感性数据集，EOC 是一种罕见的妇科恶性肿瘤，死亡率很高。这在五个 EOC 组织型中鉴定出了 155 个独特的候选 EOC 风险基因；83%（105/127）的高级别浆液性卵巢癌风险基因以前没有被牵连到这种 EOC 组织型中。chromMAGMA 提名的风险基因集中在 mRNA 剪接和转录失调途径上。chromMAGMA 是一种通过基因调控为重点的方法来提名候选风险基因的管道，并有助于解释复杂疾病中非编码风险变异的生物学机制。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/9c8f/9251535/77bdf0b01ba7/LSA-2022-01446_FigS4.jpg
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https://cdn.ncbi.nlm.nih.gov/pmc/blobs/9c8f/9251535/77bdf0b01ba7/LSA-2022-01446_FigS4.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/9c8f/9251535/2d71afca78fc/LSA-2022-01446_GA.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/9c8f/9251535/4ec39bf91f25/LSA-2022-01446_Fig1.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/9c8f/9251535/83205d086044/LSA-2022-01446_FigS1.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/9c8f/9251535/feea0125013d/LSA-2022-01446_FigS2.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/9c8f/9251535/7428a6cf4f0b/LSA-2022-01446_Fig2.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/9c8f/9251535/2a9dec336bea/LSA-2022-01446_FigS3.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/9c8f/9251535/8f92be06a1cc/LSA-2022-01446_Fig3.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/9c8f/9251535/9a9ecd9ce09a/LSA-2022-01446_Fig4.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/9c8f/9251535/9c2f2d4b734e/LSA-2022-01446_Fig5.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/9c8f/9251535/77bdf0b01ba7/LSA-2022-01446_FigS4.jpg

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本文引用的文献

1
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Nat Genet. 2021 Dec;53(12):1698-1711. doi: 10.1038/s41588-021-00972-2. Epub 2021 Dec 2.
2
Predicting master transcription factors from pan-cancer expression data.从泛癌表达数据中预测主转录因子。
Sci Adv. 2021 Nov 26;7(48):eabf6123. doi: 10.1126/sciadv.abf6123. Epub 2021 Nov 24.
3
Pleiotropy-guided transcriptome imputation from normal and tumor tissues identifies candidate susceptibility genes for breast and ovarian cancer.
Int J Mol Sci. 2022 Nov 9;23(22):13777. doi: 10.3390/ijms232213777.
基于正常组织和肿瘤组织的多效性引导转录组插补识别乳腺癌和卵巢癌的候选易感基因。
HGG Adv. 2021 Jul 8;2(3). doi: 10.1016/j.xhgg.2021.100042. Epub 2021 Jun 16.
4
Distinct Foxp3 enhancer elements coordinate development, maintenance, and function of regulatory T cells.不同的 Foxp3 增强子元件协调调节性 T 细胞的发育、维持和功能。
Immunity. 2021 May 11;54(5):947-961.e8. doi: 10.1016/j.immuni.2021.04.005. Epub 2021 Apr 29.
5
PAX8 and MECOM are interaction partners driving ovarian cancer.PAX8 和 MECOM 是驱动卵巢癌的相互作用伙伴。
Nat Commun. 2021 Apr 26;12(1):2442. doi: 10.1038/s41467-021-22708-w.
6
Genome-wide enhancer maps link risk variants to disease genes.全基因组增强子图谱将风险变异与疾病基因联系起来。
Nature. 2021 May;593(7858):238-243. doi: 10.1038/s41586-021-03446-x. Epub 2021 Apr 7.
7
Transcription factors in epithelial ovarian cancer: histotype-specific drivers and novel therapeutic targets.上皮性卵巢癌中的转录因子：组织型特异性驱动因子和新的治疗靶点。
Pharmacol Ther. 2021 Apr;220:107722. doi: 10.1016/j.pharmthera.2020.107722. Epub 2020 Nov 1.
8
Ovarian Cancer Risk Variants Are Enriched in Histotype-Specific Enhancers and Disrupt Transcription Factor Binding Sites.卵巢癌风险变异在组织亚型特异性增强子中富集，并破坏转录因子结合位点。
Am J Hum Genet. 2020 Oct 1;107(4):622-635. doi: 10.1016/j.ajhg.2020.08.021. Epub 2020 Sep 17.
9
Non-coding somatic mutations converge on the PAX8 pathway in ovarian cancer.非编码体突变在卵巢癌中汇聚于 PAX8 通路。
Nat Commun. 2020 Apr 24;11(1):2020. doi: 10.1038/s41467-020-15951-0.
10
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Nat Neurosci. 2020 Apr;23(4):583-593. doi: 10.1038/s41593-020-0603-0. Epub 2020 Mar 9.