Gene hunting with hidden Markov model knockoffs

Biometrika
M SesiaE J Candès

Abstract

Modern scientific studies often require the identification of a subset of explanatory variables. Several statistical methods have been developed to automate this task, and the framework of knockoffs has been proposed as a general solution for variable selection under rigorous Type I error control, without relying on strong modelling assumptions. In this paper, we extend the methodology of knockoffs to problems where the distribution of the covariates can be described by a hidden Markov model. We develop an exact and efficient algorithm to sample knockoff variables in this setting and then argue that, combined with the existing selective framework, this provides a natural and powerful tool for inference in genome-wide association studies with guaranteed false discovery rate control. We apply our method to datasets on Crohn's disease and some continuous phenotypes.

References

Feb 4, 1994·Journal of Molecular Biology·A KroghD Haussler
Apr 1, 1996·Computer Applications in the Biosciences : CABIOS·R Hughey, A Krogh
Mar 20, 2001·American Journal of Human Genetics·M StephensP Donnelly
May 29, 2002·Proceedings of the National Academy of Sciences of the United States of America·Kui ZhangFengzhu Sun
Jul 29, 2003·Proceedings of the National Academy of Sciences of the United States of America·John D Storey, Robert Tibshirani
Aug 5, 2003·Nature Reviews. Genetics·Jeffrey D Wall, Jonathan K Pritchard
Jul 22, 2004·Nature Reviews. Genetics·Orjan Carlborg, Chris S Haley
Dec 14, 2004·Genetic Epidemiology·Alexandre BureauPaul Van Eerdewegh
Jun 15, 2006·American Journal of Human Genetics·Hua TangNeil Risch
Jun 19, 2007·Nature Genetics·Jonathan MarchiniPeter Donnelly
Sep 28, 2007·Nature Genetics·Matthew D MailmanStephen T Sherry
Jul 26, 2008·PLoS Genetics·Clive J HoggartDavid J Balding
Dec 6, 2008·PLoS Genetics·Yongtao Guan, Matthew Stephens
Jan 30, 2009·Bioinformatics·Tong Tong WuKenneth Lange
Aug 6, 2009·Bioinformatics·Zhi WeiHakon Hakonarson
Oct 9, 2009·Nature·Teri A ManolioPeter M Visscher
Jun 3, 2010·Nature Reviews. Genetics·Jonathan Marchini, Bryan Howie
Nov 9, 2010·Genetic Epidemiology·Yun LiGonçalo R Abecasis
Dec 16, 2010·Bioinformatics·Jiahan LiRongling Wu
Sep 17, 2011·Nature Reviews. Genetics·Sharon R Browning, Brian L Browning
Oct 20, 2011·Genetic Epidemiology·David H Alexander, Kenneth Lange
Jan 10, 2012·Proceedings of the National Academy of Sciences of the United States of America·Or ZukEric S Lander
Mar 1, 2012·Nature Methods·Jason Ernst, Manolis Kellis
Aug 12, 2014·Genetics·Farhad HormozdiariEleazar Eskin
Oct 28, 2016·Genetics·Damian BrzyskiChiara Sabatti
Feb 2, 2017·Nature·Eirini MarouliGuillaume Lettre

❮ Previous
Next ❯

Citations

Jun 20, 2020·Journal of Magnetic Resonance Imaging : JMRI·Cinthia Cruz-RomeroMichael S Gee
Feb 29, 2020·Nature Communications·Matteo SesiaChiara Sabatti
Sep 20, 2020·Proceedings of the National Academy of Sciences of the United States of America·Stephen BatesEmmanuel Candès
Nov 7, 2019·The Annals of Applied Statistics·Eugene Katsevich, Chiara Sabatti
May 18, 2021·Genetic Epidemiology·Anna C Reisetter, Patrick Breheny
Jul 31, 2021·Statistics in Medicine·Konstantinos SechidisDavid Ohlssen
Sep 5, 2021·Proceedings of the National Academy of Sciences of the United States of America·Zifan ZhuFengzhu Sun

❮ Previous
Next ❯

Related Concepts

Trending Feeds

COVID-19

Coronaviruses encompass a large family of viruses that cause the common cold as well as more serious diseases, such as the ongoing outbreak of coronavirus disease 2019 (COVID-19; formally known as 2019-nCoV). Coronaviruses can spread from animals to humans; symptoms include fever, cough, shortness of breath, and breathing difficulties; in more severe cases, infection can lead to death. This feed covers recent research on COVID-19.

Blastomycosis

Blastomycosis fungal infections spread through inhaling Blastomyces dermatitidis spores. Discover the latest research on blastomycosis fungal infections here.

Nuclear Pore Complex in ALS/FTD

Alterations in nucleocytoplasmic transport, controlled by the nuclear pore complex, may be involved in the pathomechanism underlying multiple neurodegenerative diseases including Amyotrophic Lateral Sclerosis and Frontotemporal Dementia. Here is the latest research on the nuclear pore complex in ALS and FTD.

Applications of Molecular Barcoding

The concept of molecular barcoding is that each original DNA or RNA molecule is attached to a unique sequence barcode. Sequence reads having different barcodes represent different original molecules, while sequence reads having the same barcode are results of PCR duplication from one original molecule. Discover the latest research on molecular barcoding here.

Chronic Fatigue Syndrome

Chronic fatigue syndrome is a disease characterized by unexplained disabling fatigue; the pathology of which is incompletely understood. Discover the latest research on chronic fatigue syndrome here.

Evolution of Pluripotency

Pluripotency refers to the ability of a cell to develop into three primary germ cell layers of the embryo. This feed focuses on the mechanisms that underlie the evolution of pluripotency. Here is the latest research.

Position Effect Variegation

Position Effect Variagation occurs when a gene is inactivated due to its positioning near heterochromatic regions within a chromosome. Discover the latest research on Position Effect Variagation here.

STING Receptor Agonists

Stimulator of IFN genes (STING) are a group of transmembrane proteins that are involved in the induction of type I interferon that is important in the innate immune response. The stimulation of STING has been an active area of research in the treatment of cancer and infectious diseases. Here is the latest research on STING receptor agonists.

Microbicide

Microbicides are products that can be applied to vaginal or rectal mucosal surfaces with the goal of preventing, or at least significantly reducing, the transmission of sexually transmitted infections. Here is the latest research on microbicides.

Related Papers

The Journal of Family Planning and Reproductive Health Care
Pamela Warner
Journal of the American Statistical Association
Bin ZhuPeter X-K Song
Tanpakushitsu kakusan koso. Protein, nucleic acid, enzyme
T Yada
© 2022 Meta ULC. All rights reserved