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A reference map of the human binary protein interactome 期刊论文
NATURE, 2020, 580 (7803) : 402-+
作者:  Fan, Chen;  Sukomon, Nattakan;  Flood, Emelie;  Rheinberger, Jan;  Allen, Toby W.;  Nimigean, Crina M.
收藏  |  浏览/下载:6/0  |  提交时间:2020/07/03

Global insights into cellular organization and genome function require comprehensive understanding of the interactome networks that mediate genotype-phenotype relationships(1,2). Here we present a human '  all-by-all'  reference interactome map of human binary protein interactions, or '  HuRI'  . With approximately 53,000 protein-protein interactions, HuRI has approximately four times as many such interactions as there are high-quality curated interactions from small-scale studies. The integration of HuRI with genome(3), transcriptome(4) and proteome(5) data enables cellular function to be studied within most physiological or pathological cellular contexts. We demonstrate the utility of HuRI in identifying the specific subcellular roles of protein-protein interactions. Inferred tissue-specific networks reveal general principles for the formation of cellular context-specific functions and elucidate potential molecular mechanisms that might underlie tissue-specific phenotypes of Mendelian diseases. HuRI is a systematic proteome-wide reference that links genomic variation to phenotypic outcomes.


  
The strength and pattern of natural selection on gene expression in rice 期刊论文
NATURE, 2020, 578 (7796) : 572-+
作者:  Lipson, Mark;  Ribot, Isabelle;  Mallick, Swapan;  Rohland, Nadin;  Olalde, Inigo;  Adamski, Nicole;  Broomandkhoshbacht, Nasreen;  Lawson, Ann Marie;  Lopez, Saioa;  Oppenheimer, Jonas;  Stewardson, Kristin
收藏  |  浏览/下载:19/0  |  提交时间:2020/07/03

Levels of gene expression underpin organismal phenotypes(1,2), but the nature of selection that acts on gene expression and its role in adaptive evolution remain unknown(1,2). Here we assayed gene expression in rice (Oryza sativa)(3), and used phenotypic selection analysis to estimate the type and strength of selection on the levels of more than 15,000 transcripts(4,5). Variation in most transcripts appears (nearly) neutral or under very weak stabilizing selection in wet paddy conditions (with median standardized selection differentials near zero), but selection is stronger under drought conditions. Overall, more transcripts are conditionally neutral (2.83%) than are antagonistically pleiotropic(6) (0.04%), and transcripts that display lower levels of expression and stochastic noise(7-9) and higher levels of plasticity(9) are under stronger selection. Selection strength was further weakly negatively associated with levels of cis-regulation and network connectivity(9). Our multivariate analysis suggests that selection acts on the expression of photosynthesis genes(4,5), but that the efficacy of selection is genetically constrained under drought conditions(10). Drought selected for earlier flowering(11,12) and a higher expression of OsMADS18 (Os07g0605200), which encodes a MADS-box transcription factor and is a known regulator of early flowering(13)-marking this gene as a drought-escape gene(11,12). The ability to estimate selection strengths provides insights into how selection can shape molecular traits at the core of gene action.


Phenotypic selection analysis is used to estimate the type and strength of selection that acts on more than 15,000 transcripts in rice (Oryza sativa), which provides insight into the adaptive evolutionary role of selection on gene expression.


  
Deconstructing the sources of genotype-phenotype associations in humans 期刊论文
SCIENCE, 2019, 365 (6460) : 1396-1400
作者:  Young, Alexander I.;  Benonisdottir, Stefania;  Przeworski, Molly;  Kong, Augustine
收藏  |  浏览/下载:5/0  |  提交时间:2019/11/27
A key metabolic gene for recurrent freshwater colonization and radiation in fishes 期刊论文
SCIENCE, 2019, 364 (6443) : 886-+
作者:  Ishikawa, Asano;  Kabeya, Naoki;  Ikeya, Koki;  Kakioka, Ryo;  Cech, Jennifer N.;  Osada, Naoki;  Leal, Miguel C.;  Inoue, Jun;  Kume, Manabu;  Toyoda, Atsushi;  Tezuka, Ayumi;  Nagano, Atsushi J.;  Yamasaki, Yo Y.;  Suzuki, Yuto;  Kokita, Tomoyuki;  Takahashi, Hiroshi;  Lucek, Kay;  Marques, David;  Takehana, Yusuke;  Naruse, Kiyoshi;  Mori, Seiichi;  Monroig, Oscar;  Ladd, Nemiah;  Schubert, Carsten J.;  Matthews, Blake;  Peichel, Catherine L.;  Seehausen, Ole;  Yoshizaki, Goro;  Kitano, Jun
收藏  |  浏览/下载:11/0  |  提交时间:2019/11/27
Destabilizing mutations encode nongenetic variation that drives evolutionary innovation 期刊论文
SCIENCE, 2018, 359 (6383) : 1542-1545
作者:  Petrie, Katherine L.;  Palmer, Nathan D.;  Johnson, Daniel T.;  Medina, Sarah J.;  Yan, Stephanie J.;  Li, Victor;  Burmeister, Alita R.;  Meyer, Justin R.
收藏  |  浏览/下载:6/0  |  提交时间:2019/11/27
Basal resistance enhances warming tolerance of alien over indigenous species across latitude 期刊论文
PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA, 2018, 115 (1) : 145-150
作者:  Janion-Scheepers, Charlene;  Phillips, Laura;  Sgro, Carla M.;  Duffy, Grant A.;  Hallas, Rebecca;  Chown, Steven L.
收藏  |  浏览/下载:8/0  |  提交时间:2019/11/27
climate change  introduced species  soil fauna  thermal limits  laboratory evolution  
Common genetic variation drives molecular heterogeneity in human iPSCs 期刊论文
NATURE, 2017, 546 (7658) : 370-+
作者:  Kilpinen, Helena;  Goncalves, Angela;  Leha, Andreas;  Afzal, Vackar;  Alasoo, Kaur;  Ashford, Sofie;  Bala, Sendu;  Bensaddek, Dalila;  Casale, Francesco Paolo;  Ulley, Oliver J. C.;  Danecek, Petr;  Faulconbridge, Adam;  Harrison, Peter W.;  Kathuria, Annie;  McCarthy, Davis;  McCarthy, Shane A.;  Meleckyte, Ruta;  Memari, Yasin;  Moens, Nathalie;  Soares, Filipa;  Mann, Alice;  Streeter, Ian;  Agu, Chukwuma A.;  Alderton, Alex;  Nelson, Rachel;  Harper, Sarah;  Patel, Minal;  White, Alistair;  Patel, Sharad R.;  Clarke, Laura;  Halai, Reena;  Kirton, Christopher M.;  Kolb-Kokocinski, Anja;  Beales, Philip;  Birney, Ewan;  Danovi, Davide;  Lamond, Angus I.;  Ouwehand, Willem H.;  Vallier, Ludovic;  Watt, Fiona M.;  Durbin, Richard;  Stegle, Oliver;  Gaffney, Daniel J.
收藏  |  浏览/下载:14/0  |  提交时间:2019/11/27
Biased partitioning of the multidrug efflux pump AcrAB-TolC underlies long-lived phenotypic heterogeneity 期刊论文
SCIENCE, 2017, 356 (6335) : 309-311
作者:  Bergmiller, Tobias;  Andersson, Anna M. C.;  Tomasek, Kathrin;  Balleza, Enrique;  Kiviet, Daniel J.;  Hauschild, Robert;  Tkacik, Gasper;  Guet, Calin C.
收藏  |  浏览/下载:11/0  |  提交时间:2019/11/27
Human knockouts and phenotypic analysis in a cohort with a high rate of consanguinity 期刊论文
NATURE, 2017, 544 (7649) : 235-+
作者:  Saleheen, Danish;  39;Donnell-Luria, Anne H.
收藏  |  浏览/下载:0/0  |  提交时间:2019/04/09