Nền tảng MR-Base hỗ trợ suy diễn nguyên nhân một cách hệ thống trên toàn bộ biểu hiện ở người

eLife - Tập 7
Gibran Hemani1,2, Jie Zheng3,4,5,1,6,7,8, Benjamin Elsworth3,4,5,1,6,7,8, Kaitlin H. Wade3,4,5,1,6,7,8, Valeriia Haberland3,4,5,1,6,7,8, Denis Baird3,4,5,1,6,7,8, Charles Laurin3,4,5,1,6,7,8, Stephen Burgess9, Jack Bowden1,2, Ryan Langdon1,2, Vanessa Y. Tan1,2, James Yarmolinsky1,2, Hashem A. Shihab1,2, Nicholas J. Timpson1,2, David M. Evans1,2,10,11, Caroline L. Relton1,2, Richard M. Martin1,2, George Davey Smith3,4,5,1,6,7,8, Tom R. Gaunt1,2, Philip Haycock1,2
1Medical Research Council (MRC) Integrative Epidemiology Unit, Population Health Sciences, Bristol Medical School, University of Bristol, Bristol, United Kingdom
2National Institute for Health Research NIHR Bristol BRC
3Australian Research Council
4Cancer Research UK Population Research Postdoctoral Fellowship, C52724/A20138
5Castle Lung Cancer Foun-dation
6Medical Research Council Methodology Research Fellowship, MR/N501906/
7National Health and Medical Research Council.
8The Icahn School of Medicine at Mount Sinai, United States
9Department of Public Health and Primary Care, University of Cambridge, Cambridge, United Kingdom
10University of Queensland Diamantina Institute
11University of Queensland Diamantina Institute, Translational Research Institute, Brisbane, Australia

Tóm tắt

Những kết quả từ các nghiên cứu liên kết toàn bộ genome (GWAS) có thể được sử dụng để suy diễn các mối quan hệ nguyên nhân giữa các kiểu hình, bằng cách sử dụng một chiến lược được gọi là ngẫu nhiên Mendel hai mẫu (2SMR) và vượt qua nhu cầu dữ liệu cấp cá nhân. Tuy nhiên, các phương pháp 2SMR đang phát triển nhanh chóng và kết quả GWAS thường không được quản lý đầy đủ, làm giảm hiệu quả triển khai của phương pháp này. Do đó, chúng tôi đã phát triển MR-Base (http://www.mrbase.org): một nền tảng tích hợp cơ sở dữ liệu được biên soạn từ các kết quả GWAS hoàn chỉnh (không có hạn chế theo ý nghĩa thống kê) với một giao diện lập trình ứng dụng, ứng dụng web và các gói R tự động hóa 2SMR. Phần mềm bao gồm một số phân tích nhạy cảm để đánh giá tác động của sự đa hợp kém chiều ngang và các vi phạm giả định khác. Cơ sở dữ liệu hiện tại bao gồm 11 tỷ liên kết đa hình nucleotide đơn-đặc tính từ 1673 GWAS và được cập nhật thường xuyên. Việc tích hợp dữ liệu với phần mềm đảm bảo áp dụng nghiêm ngặt hơn các phân tích dựa trên giả thuyết và cho phép đánh giá hiệu quả hàng triệu mối quan hệ nguyên nhân tiềm năng trong các nghiên cứu liên kết biểu hiện rộng rãi.

Từ khóa


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