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An automated framework for efficiently designing deep convolutional neural networks in genomics [article]

Zijun Zhang, Christopher Y Park, Chandra L. Theesfeld, Olga G. Troyanskaya
<span title="2020-08-19">2020</span> <i title="Cold Spring Harbor Laboratory"> bioRxiv </i> &nbsp; <span class="release-stage" >pre-print</span>
Convolutional neural networks (CNNs) have become a standard for analysis of biological sequences. Tuning of network architectures is essential for CNN's performance, yet it requires substantial knowledge of machine learning and commitment of time and effort. This process thus imposes a major barrier to broad and effective application of modern deep learning in genomics. Here, we present AMBER, a fully automated framework to efficiently design and apply CNNs for genomic sequences. AMBER designs
more &raquo; ... ptimal models for user-specified biological questions through the state-of-the-art Neural Architecture Search (NAS). We applied AMBER to the task of modelling genomic regulatory features and demonstrated that the predictions of the AMBER-designed model are significantly more accurate than the equivalent baseline non-NAS models and match or even exceed published expert-designed models. Interpretation of AMBER architecture search revealed its design principles of utilizing the full space of computational operations for accurately modelling genomic sequences. Furthermore, we illustrated the use of AMBER to accurately discover functional genomic variants in allele-specific binding and disease heritability enrichment. AMBER provides an efficient automated method for designing accurate deep learning models in genomics.
<span class="external-identifiers"> <a target="_blank" rel="external noopener noreferrer" href="https://doi.org/10.1101/2020.08.18.251561">doi:10.1101/2020.08.18.251561</a> <a target="_blank" rel="external noopener" href="https://fatcat.wiki/release/34s7gnb66jah7mkytm2lgmmony">fatcat:34s7gnb66jah7mkytm2lgmmony</a> </span>
<a target="_blank" rel="noopener" href="https://web.archive.org/web/20201211022219/https://www.biorxiv.org/content/biorxiv/early/2020/08/19/2020.08.18.251561.full.pdf" title="fulltext PDF download" data-goatcounter-click="serp-fulltext" data-goatcounter-title="serp-fulltext"> <button class="ui simple right pointing dropdown compact black labeled icon button serp-button"> <i class="icon ia-icon"></i> Web Archive [PDF] <div class="menu fulltext-thumbnail"> <img src="https://blobs.fatcat.wiki/thumbnail/pdf/93/1d/931ddc0c250e9c051f1944bb65db06918d5769ee.180px.jpg" alt="fulltext thumbnail" loading="lazy"> </div> </button> </a> <a target="_blank" rel="external noopener noreferrer" href="https://doi.org/10.1101/2020.08.18.251561"> <button class="ui left aligned compact blue labeled icon button serp-button"> <i class="external alternate icon"></i> biorxiv.org </button> </a>

Discovery of biological networks from diverse functional genomic data

Chad L Myers, Drew Robson, Adam Wible, Matthew A Hibbs, Camelia Chiriac, Chandra L Theesfeld, Kara Dolinski, Olga G Troyanskaya
<span title="2005-12-19">2005</span> <i title="BMC"> <a target="_blank" rel="noopener" href="https://fatcat.wiki/container/6bzsiicmhvczjnsm7jbog7ysaa" style="color: black;">Genome Biology</a> </i> &nbsp;
We have developed a general probabilistic system for query-based discovery of pathway-specific networks through integration of diverse genome-wide data. This framework was validated by accurately recovering known networks for 31 biological processes in Saccharomyces cerevisiae and experimentally verifying predictions for the process of chromosomal segregation. Our system, bioPIXIE, a public, comprehensive system for integration, analysis, and visualization of biological network predictions for
more &raquo; ... . cerevisiae, is freely accessible over the worldwide web.
<span class="external-identifiers"> <a target="_blank" rel="external noopener noreferrer" href="https://doi.org/10.1186/gb-2005-6-13-r114">doi:10.1186/gb-2005-6-13-r114</a> <a target="_blank" rel="external noopener" href="https://www.ncbi.nlm.nih.gov/pubmed/16420673">pmid:16420673</a> <a target="_blank" rel="external noopener" href="https://pubmed.ncbi.nlm.nih.gov/PMC1414113/">pmcid:PMC1414113</a> <a target="_blank" rel="external noopener" href="https://fatcat.wiki/release/zbwq3u3eufebrdbwqlikgteljq">fatcat:zbwq3u3eufebrdbwqlikgteljq</a> </span>
<a target="_blank" rel="noopener" href="https://web.archive.org/web/20190428000955/https://genomebiology.biomedcentral.com/track/pdf/10.1186/gb-2005-6-13-r114" title="fulltext PDF download" data-goatcounter-click="serp-fulltext" data-goatcounter-title="serp-fulltext"> <button class="ui simple right pointing dropdown compact black labeled icon button serp-button"> <i class="icon ia-icon"></i> Web Archive [PDF] <div class="menu fulltext-thumbnail"> <img src="https://blobs.fatcat.wiki/thumbnail/pdf/37/8c/378c0066bfb4b2c775028db69eab11cc6b4791a1.180px.jpg" alt="fulltext thumbnail" loading="lazy"> </div> </button> </a> <a target="_blank" rel="external noopener noreferrer" href="https://doi.org/10.1186/gb-2005-6-13-r114"> <button class="ui left aligned compact blue labeled icon button serp-button"> <i class="unlock alternate icon" style="background-color: #fb971f;"></i> Publisher / doi.org </button> </a> <a target="_blank" rel="external noopener" href="https://www.ncbi.nlm.nih.gov/pmc/articles/PMC1414113" title="pubmed link"> <button class="ui compact blue labeled icon button serp-button"> <i class="file alternate outline icon"></i> pubmed.gov </button> </a>

Opposing Roles for Actin in Cdc42p Polarization

Javier E. Irazoqui, Audrey S. Howell, Chandra L. Theesfeld, Daniel J. Lew
<span title="">2005</span> <i title="American Society for Cell Biology (ASCB)"> <a target="_blank" rel="noopener" href="https://fatcat.wiki/container/btmjitlxs5by3dntmzk67gakxi" style="color: black;">Molecular Biology of the Cell</a> </i> &nbsp;
(C) Lawns of wild-type (ACT1: DDY354) and latrunculin-resistant actin mutant (act1-117: DDY345) cells were spread on YEPD plates, sterile paper discs spotted with 10 l DMSO (control), Lat A (2 mM), or  ... 
<span class="external-identifiers"> <a target="_blank" rel="external noopener noreferrer" href="https://doi.org/10.1091/mbc.e04-05-0430">doi:10.1091/mbc.e04-05-0430</a> <a target="_blank" rel="external noopener" href="https://www.ncbi.nlm.nih.gov/pubmed/15616194">pmid:15616194</a> <a target="_blank" rel="external noopener" href="https://pubmed.ncbi.nlm.nih.gov/PMC551493/">pmcid:PMC551493</a> <a target="_blank" rel="external noopener" href="https://fatcat.wiki/release/ormtlk5fxvg6zp2ejnkel3xojy">fatcat:ormtlk5fxvg6zp2ejnkel3xojy</a> </span>
<a target="_blank" rel="noopener" href="https://web.archive.org/web/20200507010431/http://europepmc.org/backend/ptpmcrender.fcgi?accid=PMC551493&amp;blobtype=pdf" title="fulltext PDF download" data-goatcounter-click="serp-fulltext" data-goatcounter-title="serp-fulltext"> <button class="ui simple right pointing dropdown compact black labeled icon button serp-button"> <i class="icon ia-icon"></i> Web Archive [PDF] <div class="menu fulltext-thumbnail"> <img src="https://blobs.fatcat.wiki/thumbnail/pdf/fd/4a/fd4add659f8536337302ffe99dfc5a468a9f83bc.180px.jpg" alt="fulltext thumbnail" loading="lazy"> </div> </button> </a> <a target="_blank" rel="external noopener noreferrer" href="https://doi.org/10.1091/mbc.e04-05-0430"> <button class="ui left aligned compact blue labeled icon button serp-button"> <i class="external alternate icon"></i> Publisher / doi.org </button> </a> <a target="_blank" rel="external noopener" href="https://www.ncbi.nlm.nih.gov/pmc/articles/PMC551493" title="pubmed link"> <button class="ui compact blue labeled icon button serp-button"> <i class="file alternate outline icon"></i> pubmed.gov </button> </a>

DeepArk: modeling cis-regulatory codes of model species with deep learning [article]

Evan M Cofer, João Raimundo, Alicja Tadych, Yuji Yamazaki, Aaron K Wong, Chandra L Theesfeld, Michael S Levine, Olga G Troyanskaya
<span title="2020-04-25">2020</span> <i title="Cold Spring Harbor Laboratory"> bioRxiv </i> &nbsp; <span class="release-stage" >pre-print</span>
To enable large-scale analyses of regulatory logic in model species, we developed DeepArk (https://DeepArk.princeton.edu), a set of deep learning models of the cis-regulatory codes of four widely-studied species: Caenorhabditis elegans, Danio rerio, Drosophila melanogaster, and Mus musculus. DeepArk accurately predicts the presence of thousands of different context-specific regulatory features, including chromatin states, histone marks, and transcription factors. In vivo studies show that
more &raquo; ... k can predict the regulatory impact of any genomic variant (including rare or not previously observed), and enables the regulatory annotation of understudied model species.
<span class="external-identifiers"> <a target="_blank" rel="external noopener noreferrer" href="https://doi.org/10.1101/2020.04.23.058040">doi:10.1101/2020.04.23.058040</a> <a target="_blank" rel="external noopener" href="https://fatcat.wiki/release/ntzwl6iph5auvic4utt4rkefuq">fatcat:ntzwl6iph5auvic4utt4rkefuq</a> </span>
<a target="_blank" rel="noopener" href="https://web.archive.org/web/20201103061325/https://www.biorxiv.org/content/biorxiv/early/2020/04/28/2020.04.23.058040.full.pdf" title="fulltext PDF download" data-goatcounter-click="serp-fulltext" data-goatcounter-title="serp-fulltext"> <button class="ui simple right pointing dropdown compact black labeled icon button serp-button"> <i class="icon ia-icon"></i> Web Archive [PDF] <div class="menu fulltext-thumbnail"> <img src="https://blobs.fatcat.wiki/thumbnail/pdf/a5/40/a540433a2a33a42e89216c29265bd801bf5c9d15.180px.jpg" alt="fulltext thumbnail" loading="lazy"> </div> </button> </a> <a target="_blank" rel="external noopener noreferrer" href="https://doi.org/10.1101/2020.04.23.058040"> <button class="ui left aligned compact blue labeled icon button serp-button"> <i class="external alternate icon"></i> biorxiv.org </button> </a>

The Role of Actin in Spindle Orientation Changes during theSaccharomyces cerevisiaeCell Cycle

Chandra L. Theesfeld, Javier E. Irazoqui, Kerry Bloom, Daniel J. Lew
<span title="1999-09-06">1999</span> <i title="Rockefeller University Press"> <a target="_blank" rel="noopener" href="https://fatcat.wiki/container/ye43mmowdfaidn3yibreupuvq4" style="color: black;">Journal of Cell Biology</a> </i> &nbsp;
In the budding yeast Saccharomyces cerevisiae , the mitotic spindle must align along the motherbud axis to accurately partition the sister chromatids into daughter cells. Previous studies showed that spindle orientation required both astral microtubules and the actin cytoskeleton. We now report that maintenance of correct spindle orientation does not depend on F-actin during G2/M phase of the cell cycle. Depolymerization of F-actin using Latrunculin-A did not perturb spindle orientation after
more &raquo; ... is stage. Even an early step in spindle orientation, the migration of the spindle pole body (SPB), became actin-independent if it was delayed until late in the cell cycle. Early in the cell cycle, both SPB migration and spindle orientation were very sensitive to perturbation of F-actin. Selective disruption of actin cables using a conditional tropomyosin double-mutant also led to defects in spindle orientation, even though cortical actin patches were still polarized. This suggests that actin cables are important for either guiding astral microtubules into the bud or anchoring them in the bud. In addition, F-actin was required early in the cell cycle for the development of the actin-independent spindle orientation capability later in the cell cycle. Finally, neither SPB migration nor the switch from actin-dependent to actin-independent spindle behavior required B-type cyclins.
<span class="external-identifiers"> <a target="_blank" rel="external noopener noreferrer" href="https://doi.org/10.1083/jcb.146.5.1019">doi:10.1083/jcb.146.5.1019</a> <a target="_blank" rel="external noopener" href="https://www.ncbi.nlm.nih.gov/pubmed/10477756">pmid:10477756</a> <a target="_blank" rel="external noopener" href="https://pubmed.ncbi.nlm.nih.gov/PMC2169477/">pmcid:PMC2169477</a> <a target="_blank" rel="external noopener" href="https://fatcat.wiki/release/gwhzmftdcze2rfetef5trocv6a">fatcat:gwhzmftdcze2rfetef5trocv6a</a> </span>
<a target="_blank" rel="noopener" href="https://web.archive.org/web/20170813005604/http://labs.bio.unc.edu/Bloom/pdf/theesfeld.pdf" title="fulltext PDF download" data-goatcounter-click="serp-fulltext" data-goatcounter-title="serp-fulltext"> <button class="ui simple right pointing dropdown compact black labeled icon button serp-button"> <i class="icon ia-icon"></i> Web Archive [PDF] <div class="menu fulltext-thumbnail"> <img src="https://blobs.fatcat.wiki/thumbnail/pdf/22/4e/224ee72bfe323242c502803d2c1a75a21ca4c499.180px.jpg" alt="fulltext thumbnail" loading="lazy"> </div> </button> </a> <a target="_blank" rel="external noopener noreferrer" href="https://doi.org/10.1083/jcb.146.5.1019"> <button class="ui left aligned compact blue labeled icon button serp-button"> <i class="external alternate icon"></i> Publisher / doi.org </button> </a> <a target="_blank" rel="external noopener" href="https://www.ncbi.nlm.nih.gov/pmc/articles/PMC2169477" title="pubmed link"> <button class="ui compact blue labeled icon button serp-button"> <i class="file alternate outline icon"></i> pubmed.gov </button> </a>

A Monitor for Bud Emergence in the Yeast Morphogenesis Checkpoint

Chandra L. Theesfeld, Trevin R. Zyla, Elaine G.S. Bardes, Daniel J. Lew
<span title="">2003</span> <i title="American Society for Cell Biology (ASCB)"> <a target="_blank" rel="noopener" href="https://fatcat.wiki/container/btmjitlxs5by3dntmzk67gakxi" style="color: black;">Molecular Biology of the Cell</a> </i> &nbsp;
Theesfeld et al.  ...  Theesfeld et al. function in Swe1p down-regulation in vivo.  ... 
<span class="external-identifiers"> <a target="_blank" rel="external noopener noreferrer" href="https://doi.org/10.1091/mbc.e03-03-0154">doi:10.1091/mbc.e03-03-0154</a> <a target="_blank" rel="external noopener" href="https://www.ncbi.nlm.nih.gov/pubmed/12925763">pmid:12925763</a> <a target="_blank" rel="external noopener" href="https://pubmed.ncbi.nlm.nih.gov/PMC181567/">pmcid:PMC181567</a> <a target="_blank" rel="external noopener" href="https://fatcat.wiki/release/m24thsutd5ao5hznl3y4d6vtjq">fatcat:m24thsutd5ao5hznl3y4d6vtjq</a> </span>
<a target="_blank" rel="noopener" href="https://web.archive.org/web/20200210043103/http://europepmc.org/backend/ptpmcrender.fcgi?accid=PMC181567&amp;blobtype=pdf" title="fulltext PDF download" data-goatcounter-click="serp-fulltext" data-goatcounter-title="serp-fulltext"> <button class="ui simple right pointing dropdown compact black labeled icon button serp-button"> <i class="icon ia-icon"></i> Web Archive [PDF] <div class="menu fulltext-thumbnail"> <img src="https://blobs.fatcat.wiki/thumbnail/pdf/84/d9/84d9a27fa0d3e7cd0d2247794fa1d9b4cc2a56d0.180px.jpg" alt="fulltext thumbnail" loading="lazy"> </div> </button> </a> <a target="_blank" rel="external noopener noreferrer" href="https://doi.org/10.1091/mbc.e03-03-0154"> <button class="ui left aligned compact blue labeled icon button serp-button"> <i class="external alternate icon"></i> Publisher / doi.org </button> </a> <a target="_blank" rel="external noopener" href="https://www.ncbi.nlm.nih.gov/pmc/articles/PMC181567" title="pubmed link"> <button class="ui compact blue labeled icon button serp-button"> <i class="file alternate outline icon"></i> pubmed.gov </button> </a>

Modeling transcriptional regulation of model species with deep learning

Evan M Cofer, João Raimundo, Alicja Tadych, Yuji Yamazaki, Aaron K Wong, Chandra L Theesfeld, Michael S Levine, Olga G Troyanskaya
<span title="2021-04-22">2021</span> <i title="Cold Spring Harbor Laboratory"> <a target="_blank" rel="noopener" href="https://fatcat.wiki/container/nwro4atxwbec5pfkpfslaxbdae" style="color: black;">Genome Research</a> </i> &nbsp;
Specifically, our objective function was the sum of the binary cross-entropy (BCE) loss and an L2 regularization term, L = BCE + l W 2 2 , BCE = − 1 N N i=1 y i log y i + (1 − y i )log(1 − y i ), where  ... 
<span class="external-identifiers"> <a target="_blank" rel="external noopener noreferrer" href="https://doi.org/10.1101/gr.266171.120">doi:10.1101/gr.266171.120</a> <a target="_blank" rel="external noopener" href="https://www.ncbi.nlm.nih.gov/pubmed/33888512">pmid:33888512</a> <a target="_blank" rel="external noopener" href="https://pubmed.ncbi.nlm.nih.gov/PMC8168591/">pmcid:PMC8168591</a> <a target="_blank" rel="external noopener" href="https://fatcat.wiki/release/xmdemc2xgrf4jhu5hk4wefudh4">fatcat:xmdemc2xgrf4jhu5hk4wefudh4</a> </span>
<a target="_blank" rel="noopener" href="https://web.archive.org/web/20210711062450/https://genome.cshlp.org/content/31/6/1097.full.pdf" title="fulltext PDF download" data-goatcounter-click="serp-fulltext" data-goatcounter-title="serp-fulltext"> <button class="ui simple right pointing dropdown compact black labeled icon button serp-button"> <i class="icon ia-icon"></i> Web Archive [PDF] <div class="menu fulltext-thumbnail"> <img src="https://blobs.fatcat.wiki/thumbnail/pdf/74/a4/74a4f902ac105a00b91da260c7522ca3a88d2303.180px.jpg" alt="fulltext thumbnail" loading="lazy"> </div> </button> </a> <a target="_blank" rel="external noopener noreferrer" href="https://doi.org/10.1101/gr.266171.120"> <button class="ui left aligned compact blue labeled icon button serp-button"> <i class="external alternate icon"></i> Publisher / doi.org </button> </a> <a target="_blank" rel="external noopener" href="https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8168591" title="pubmed link"> <button class="ui compact blue labeled icon button serp-button"> <i class="file alternate outline icon"></i> pubmed.gov </button> </a>

Determinants of Swe1p Degradation in Saccharomyces cerevisiae

John N. McMillan, Chandra L. Theesfeld, Jacob C. Harrison, Elaine S. G. Bardes, Daniel J. Lew, Mark J. Solomon
<span title="">2002</span> <i title="American Society for Cell Biology (ASCB)"> <a target="_blank" rel="noopener" href="https://fatcat.wiki/container/btmjitlxs5by3dntmzk67gakxi" style="color: black;">Molecular Biology of the Cell</a> </i> &nbsp;
<span class="external-identifiers"> <a target="_blank" rel="external noopener noreferrer" href="https://doi.org/10.1091/mbc.e02-05-0283">doi:10.1091/mbc.e02-05-0283</a> <a target="_blank" rel="external noopener" href="https://www.ncbi.nlm.nih.gov/pubmed/12388757">pmid:12388757</a> <a target="_blank" rel="external noopener" href="https://pubmed.ncbi.nlm.nih.gov/PMC129966/">pmcid:PMC129966</a> <a target="_blank" rel="external noopener" href="https://fatcat.wiki/release/dtije22qejboxaehyvhhnc5fme">fatcat:dtije22qejboxaehyvhhnc5fme</a> </span>
<a target="_blank" rel="noopener" href="https://web.archive.org/web/20191017113125/http://europepmc.org/backend/ptpmcrender.fcgi?accid=PMC129966&amp;blobtype=pdf" title="fulltext PDF download" data-goatcounter-click="serp-fulltext" data-goatcounter-title="serp-fulltext"> <button class="ui simple right pointing dropdown compact black labeled icon button serp-button"> <i class="icon ia-icon"></i> Web Archive [PDF] <div class="menu fulltext-thumbnail"> <img src="https://blobs.fatcat.wiki/thumbnail/pdf/88/1d/881d7de87a493a74af2565a18aa9bd6ba52a1694.180px.jpg" alt="fulltext thumbnail" loading="lazy"> </div> </button> </a> <a target="_blank" rel="external noopener noreferrer" href="https://doi.org/10.1091/mbc.e02-05-0283"> <button class="ui left aligned compact blue labeled icon button serp-button"> <i class="external alternate icon"></i> Publisher / doi.org </button> </a> <a target="_blank" rel="external noopener" href="https://www.ncbi.nlm.nih.gov/pmc/articles/PMC129966" title="pubmed link"> <button class="ui compact blue labeled icon button serp-button"> <i class="file alternate outline icon"></i> pubmed.gov </button> </a>

Genome-wide characterization of genetic and functional dysregulation in autism spectrum disorder [article]

Arjun Krishnan, Ran Zhang, Victoria Yao, Chandra L Theesfeld, Aaron K Wong, Alicja Tadych, Natalia Volfovsky, Alan Packer, Alex Lash, Olga G Troyanskaya
<span title="2016-06-09">2016</span> <i title="Cold Spring Harbor Laboratory"> bioRxiv </i> &nbsp; <span class="release-stage" >pre-print</span>
E a r l y F e t a l 2 E a r l y M i d f e t a l 1 E a r l y M i d f e t a l 2 L a t e M i d f e t a l L a t e F e t a l N e o n a t a l E a r l y I n f a n c y L a t e I n f a n c y E a r l y C h i l d  ...  h o o d M i d d l e -L a t e C h i l d h o o d A d o l e s c n e c e Y o u n g A d u l t h o o d M i d d l e A d u l t h o o d L a t e A d u l t h o o d Figure 4 : 4 Figure4: Autism-associated brain-specific  ... 
<span class="external-identifiers"> <a target="_blank" rel="external noopener noreferrer" href="https://doi.org/10.1101/057828">doi:10.1101/057828</a> <a target="_blank" rel="external noopener" href="https://fatcat.wiki/release/efy5oglidfg6zhajqclixkxw4u">fatcat:efy5oglidfg6zhajqclixkxw4u</a> </span>
<a target="_blank" rel="noopener" href="https://web.archive.org/web/20190426124910/https://www.biorxiv.org/content/biorxiv/early/2016/06/09/057828.full.pdf" title="fulltext PDF download" data-goatcounter-click="serp-fulltext" data-goatcounter-title="serp-fulltext"> <button class="ui simple right pointing dropdown compact black labeled icon button serp-button"> <i class="icon ia-icon"></i> Web Archive [PDF] <div class="menu fulltext-thumbnail"> <img src="https://blobs.fatcat.wiki/thumbnail/pdf/01/11/0111544a9ffb78d8eb364969e3e9bd20a3c90581.180px.jpg" alt="fulltext thumbnail" loading="lazy"> </div> </button> </a> <a target="_blank" rel="external noopener noreferrer" href="https://doi.org/10.1101/057828"> <button class="ui left aligned compact blue labeled icon button serp-button"> <i class="external alternate icon"></i> biorxiv.org </button> </a>

Genome-wide landscape of RNA-binding protein dysregulation reveals a major impact on psychiatric disorder risk [article]

Christopher Y Park, Jian Zhou, Aaron K Wong, Kathleen M Chen, Chandra L Theesfeld, Robert Darnell, Olga G. Troyanskaya
<span title="2020-05-20">2020</span> <i title="Cold Spring Harbor Laboratory"> bioRxiv </i> &nbsp; <span class="release-stage" >pre-print</span>
Despite the strong genetic basis of psychiatric disorders, the molecular origins of these diseases are still largely unmapped. RNA-binding proteins (RBPs) are responsible for most post- transcriptional regulation, from splicing to translational to localization. RBPs thus act as key gatekeepers of cellular homeostasis, especially in the brain. Here, we leverage a deep learning approach to interrogate variant effects genome-wide, and discover that the dysregulation of RBP target sites is a
more &raquo; ... al contributor to psychiatric disorder risk. We show that specific modes of RBP regulation are genetically linked to the heritability of psychiatric disorders, and demonstrate that diverse RBP regulatory functions are reflected in distinct genome-wide negative selection signatures. Notably, RBP dysregulation has a stronger impact on psychiatric disorders than common coding region variants and explains heritability not currently captured by large-scale molecular QTL studies (expression QTLs and splicing QTLs). We share genome-wide profiles of RBP target site dysregulation, which we used to identify DDHD2 as a candidate schizophrenia risk gene, in a public web server. This resource provides a novel analytical framework to connect the full range of RNA regulation to complex disease.
<span class="external-identifiers"> <a target="_blank" rel="external noopener noreferrer" href="https://doi.org/10.1101/2020.05.19.102319">doi:10.1101/2020.05.19.102319</a> <a target="_blank" rel="external noopener" href="https://fatcat.wiki/release/2jmtkzmo3bbvjg54przkteessi">fatcat:2jmtkzmo3bbvjg54przkteessi</a> </span>
<a target="_blank" rel="noopener" href="https://web.archive.org/web/20201108063008/https://www.biorxiv.org/content/biorxiv/early/2020/05/20/2020.05.19.102319.full.pdf" title="fulltext PDF download" data-goatcounter-click="serp-fulltext" data-goatcounter-title="serp-fulltext"> <button class="ui simple right pointing dropdown compact black labeled icon button serp-button"> <i class="icon ia-icon"></i> Web Archive [PDF] <div class="menu fulltext-thumbnail"> <img src="https://blobs.fatcat.wiki/thumbnail/pdf/1b/a4/1ba41c3dd74e1860670ec8fce82e40e27d5c4134.180px.jpg" alt="fulltext thumbnail" loading="lazy"> </div> </button> </a> <a target="_blank" rel="external noopener noreferrer" href="https://doi.org/10.1101/2020.05.19.102319"> <button class="ui left aligned compact blue labeled icon button serp-button"> <i class="external alternate icon"></i> biorxiv.org </button> </a>

Insulin-induced Gene Protein (INSIG)-dependent Sterol Regulation of Hmg2 Endoplasmic Reticulum-associated Degradation (ERAD) in Yeast

Chandra L. Theesfeld, Randolph Y. Hampton
<span title="2013-01-10">2013</span> <i title="American Society for Biochemistry &amp; Molecular Biology (ASBMB)"> <a target="_blank" rel="noopener" href="https://fatcat.wiki/container/mryncoafc5cxdicldzfm4vlsze" style="color: black;">Journal of Biological Chemistry</a> </i> &nbsp;
L. Theesfeld and R. Y.  ...  Beads were washed four times with IP Wash. 55 l of sample buffer was added to dried beads, and sample was heated at 50°C for 3 min. 80% of each sample was loaded on an 8% gel.  ... 
<span class="external-identifiers"> <a target="_blank" rel="external noopener noreferrer" href="https://doi.org/10.1074/jbc.m112.404517">doi:10.1074/jbc.m112.404517</a> <a target="_blank" rel="external noopener" href="https://www.ncbi.nlm.nih.gov/pubmed/23306196">pmid:23306196</a> <a target="_blank" rel="external noopener" href="https://pubmed.ncbi.nlm.nih.gov/PMC3605666/">pmcid:PMC3605666</a> <a target="_blank" rel="external noopener" href="https://fatcat.wiki/release/wxrap4253zdx3jbdwicva3znlu">fatcat:wxrap4253zdx3jbdwicva3znlu</a> </span>
<a target="_blank" rel="noopener" href="https://web.archive.org/web/20190222123339/http://pdfs.semanticscholar.org/3ee6/28831cb87015c839c833233327292ee4214e.pdf" title="fulltext PDF download" data-goatcounter-click="serp-fulltext" data-goatcounter-title="serp-fulltext"> <button class="ui simple right pointing dropdown compact black labeled icon button serp-button"> <i class="icon ia-icon"></i> Web Archive [PDF] <div class="menu fulltext-thumbnail"> <img src="https://blobs.fatcat.wiki/thumbnail/pdf/3e/e6/3ee628831cb87015c839c833233327292ee4214e.180px.jpg" alt="fulltext thumbnail" loading="lazy"> </div> </button> </a> <a target="_blank" rel="external noopener noreferrer" href="https://doi.org/10.1074/jbc.m112.404517"> <button class="ui left aligned compact blue labeled icon button serp-button"> <i class="unlock alternate icon" style="background-color: #fb971f;"></i> Publisher / doi.org </button> </a> <a target="_blank" rel="external noopener" href="https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3605666" title="pubmed link"> <button class="ui compact blue labeled icon button serp-button"> <i class="file alternate outline icon"></i> pubmed.gov </button> </a>

The Morphogenesis Checkpoint inSaccharomyces cerevisiae: Cell Cycle Control of Swe1p Degradation by Hsl1p and Hsl7p

John N. McMillan, Mark S. Longtine, Rey A. L. Sia, Chandra L. Theesfeld, Elaine S. G. Bardes, John R. Pringle, Daniel J. Lew
<span title="1999-10-01">1999</span> <i title="American Society for Microbiology"> <a target="_blank" rel="noopener" href="https://fatcat.wiki/container/ki5pr2lmenbmbijbb4tkftguwe" style="color: black;">Molecular and Cellular Biology</a> </i> &nbsp;
For immunoprecipitation, 200 g of lysate was incubated for 1 h with 1 l of antibody and then for a further 1 h with 30 l of a 50% slurry of protein A-Sepharose (Sigma) at 4°C with gentle rocking.  ... 
<span class="external-identifiers"> <a target="_blank" rel="external noopener noreferrer" href="https://doi.org/10.1128/mcb.19.10.6929">doi:10.1128/mcb.19.10.6929</a> <a target="_blank" rel="external noopener" href="https://www.ncbi.nlm.nih.gov/pubmed/10490630">pmid:10490630</a> <a target="_blank" rel="external noopener" href="https://pubmed.ncbi.nlm.nih.gov/PMC84688/">pmcid:PMC84688</a> <a target="_blank" rel="external noopener" href="https://fatcat.wiki/release/dyk2nipkjzfafjnqkrlqvnrpma">fatcat:dyk2nipkjzfafjnqkrlqvnrpma</a> </span>
<a target="_blank" rel="noopener" href="https://web.archive.org/web/20200507063103/https://mcb.asm.org/content/mcb/19/10/6929.full.pdf" title="fulltext PDF download" data-goatcounter-click="serp-fulltext" data-goatcounter-title="serp-fulltext"> <button class="ui simple right pointing dropdown compact black labeled icon button serp-button"> <i class="icon ia-icon"></i> Web Archive [PDF] <div class="menu fulltext-thumbnail"> <img src="https://blobs.fatcat.wiki/thumbnail/pdf/dd/dd/dddde5f9233bba6e81866f6717a4f03efb764349.180px.jpg" alt="fulltext thumbnail" loading="lazy"> </div> </button> </a> <a target="_blank" rel="external noopener noreferrer" href="https://doi.org/10.1128/mcb.19.10.6929"> <button class="ui left aligned compact blue labeled icon button serp-button"> <i class="external alternate icon"></i> asm.org </button> </a> <a target="_blank" rel="external noopener" href="https://www.ncbi.nlm.nih.gov/pmc/articles/PMC84688" title="pubmed link"> <button class="ui compact blue labeled icon button serp-button"> <i class="file alternate outline icon"></i> pubmed.gov </button> </a>

Accurate genome-wide predictions of spatio-temporal gene expression during embryonic development

Jian Zhou, Ignacio E. Schor, Victoria Yao, Chandra L. Theesfeld, Raquel Marco-Ferreres, Alicja Tadych, Eileen E. M. Furlong, Olga G. Troyanskaya, Claude Desplan
<span title="2019-09-25">2019</span> <i title="Public Library of Science (PLoS)"> <a target="_blank" rel="noopener" href="https://fatcat.wiki/container/j6fzfstrmzcj3aeps7bx6tpoy4" style="color: black;">PLoS Genetics</a> </i> &nbsp;
Comprehensive information on the timing and location of gene expression is fundamental to our understanding of embryonic development and tissue formation. While high-throughput in situ hybridization projects provide invaluable information about developmental gene expression patterns for model organisms like Drosophila, the output of these experiments is primarily qualitative, and a high proportion of protein coding genes and most non-coding genes lack any annotation. Accurate data-centric
more &raquo; ... tions of spatio-temporal gene expression will therefore complement current in situ hybridization efforts. Here, we applied a machine learning approach by training models on all public gene expression and chromatin data, even from whole-organism experiments, to provide genome-wide, quantitative spatio-temporal predictions for all genes. We developed structured in silico nano-dissection, a computational approach that predicts gene expression in >200 tissue-developmental stages. The algorithm integrates expression signals from a compendium of 6,378 genome-wide expression and chromatin profiling experiments in a cell lineage-aware fashion. We systematically evaluated our performance via cross-validation and experimentally confirmed 22 new predictions for four different embryonic tissues. The model also predicts complex, multi-tissue expression and developmental regulation with high accuracy. We further show the potential of applying these genome-wide predictions to extract tissue specificity signals from non-tissue-dissected experiments, and to prioritize tissues and stages for disease modeling. This resource, together with the exploratory tools are freely available at our webserver http://find.princeton.edu, which provides a valuable tool for a range of applications, from predicting spatio-temporal expression patterns to recognizing tissue signatures from differential gene expression profiles.
<span class="external-identifiers"> <a target="_blank" rel="external noopener noreferrer" href="https://doi.org/10.1371/journal.pgen.1008382">doi:10.1371/journal.pgen.1008382</a> <a target="_blank" rel="external noopener" href="https://www.ncbi.nlm.nih.gov/pubmed/31553718">pmid:31553718</a> <a target="_blank" rel="external noopener" href="https://pubmed.ncbi.nlm.nih.gov/PMC6779412/">pmcid:PMC6779412</a> <a target="_blank" rel="external noopener" href="https://fatcat.wiki/release/m62jcv4kibgytdxi2zmt3kzxfi">fatcat:m62jcv4kibgytdxi2zmt3kzxfi</a> </span>
<a target="_blank" rel="noopener" href="https://web.archive.org/web/20191214185807/https://journals.plos.org/plosgenetics/article/file?id=10.1371/journal.pgen.1008382&amp;type=printable" title="fulltext PDF download" data-goatcounter-click="serp-fulltext" data-goatcounter-title="serp-fulltext"> <button class="ui simple right pointing dropdown compact black labeled icon button serp-button"> <i class="icon ia-icon"></i> Web Archive [PDF] <div class="menu fulltext-thumbnail"> <img src="https://blobs.fatcat.wiki/thumbnail/pdf/c1/56/c1567acd103a38aa3cb2cad626e0f836489a68c1.180px.jpg" alt="fulltext thumbnail" loading="lazy"> </div> </button> </a> <a target="_blank" rel="external noopener noreferrer" href="https://doi.org/10.1371/journal.pgen.1008382"> <button class="ui left aligned compact blue labeled icon button serp-button"> <i class="unlock alternate icon" style="background-color: #fb971f;"></i> plos.org </button> </a> <a target="_blank" rel="external noopener" href="https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6779412" title="pubmed link"> <button class="ui compact blue labeled icon button serp-button"> <i class="file alternate outline icon"></i> pubmed.gov </button> </a>

Genome-wide prediction and functional characterization of the genetic basis of autism spectrum disorder

Arjun Krishnan, Ran Zhang, Victoria Yao, Chandra L Theesfeld, Aaron K Wong, Alicja Tadych, Natalia Volfovsky, Alan Packer, Alex Lash, Olga G Troyanskaya
<span title="2016-08-01">2016</span> <i title="Springer Nature"> <a target="_blank" rel="noopener" href="https://fatcat.wiki/container/lnbpt3q37zbs5nc5hp4wlttdwy" style="color: black;">Nature Neuroscience</a> </i> &nbsp;
By setting l i equal to the evidence-weight of the labeled gene (where negatives have l i of 1), we ensured that our model rarely misclassi-fies high-confidence genes while giving certain latitude in correctly  ...  Given the network features (x i ) and a positive/negative label (y i ) for all the m training genes, the linear SVM solves the following optimization problem 56 : where l i is a penalty parameter specific  ... 
<span class="external-identifiers"> <a target="_blank" rel="external noopener noreferrer" href="https://doi.org/10.1038/nn.4353">doi:10.1038/nn.4353</a> <a target="_blank" rel="external noopener" href="https://www.ncbi.nlm.nih.gov/pubmed/27479844">pmid:27479844</a> <a target="_blank" rel="external noopener" href="https://pubmed.ncbi.nlm.nih.gov/PMC5803797/">pmcid:PMC5803797</a> <a target="_blank" rel="external noopener" href="https://fatcat.wiki/release/eewcnklzena2fo6jbw3mtgjhpq">fatcat:eewcnklzena2fo6jbw3mtgjhpq</a> </span>
<a target="_blank" rel="noopener" href="https://web.archive.org/web/20200209104451/http://europepmc.org/backend/ptpmcrender.fcgi?accid=PMC5803797&amp;blobtype=pdf" title="fulltext PDF download" data-goatcounter-click="serp-fulltext" data-goatcounter-title="serp-fulltext"> <button class="ui simple right pointing dropdown compact black labeled icon button serp-button"> <i class="icon ia-icon"></i> Web Archive [PDF] <div class="menu fulltext-thumbnail"> <img src="https://blobs.fatcat.wiki/thumbnail/pdf/de/9a/de9ad79f290044a58e68618bbb3870ad66a7280a.180px.jpg" alt="fulltext thumbnail" loading="lazy"> </div> </button> </a> <a target="_blank" rel="external noopener noreferrer" href="https://doi.org/10.1038/nn.4353"> <button class="ui left aligned compact blue labeled icon button serp-button"> <i class="external alternate icon"></i> nature.com </button> </a> <a target="_blank" rel="external noopener" href="https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5803797" title="pubmed link"> <button class="ui compact blue labeled icon button serp-button"> <i class="file alternate outline icon"></i> pubmed.gov </button> </a>

Modeling molecular development of breast cancer in canine mammary tumors

Kiley Graim, Dmitriy Gorenshteyn, David G Robinson, Nicholas J Carriero, James Andrew Cahill, Rumela Chakrabarti, Michael H Goldschmidt, Amy C Durham, Julien Funk, John Storey, Vessela N Kristensen, Chandra L Theesfeld (+2 others)
<span title="2020-12-23">2020</span> <i title="Cold Spring Harbor Laboratory"> <a target="_blank" rel="noopener" href="https://fatcat.wiki/container/nwro4atxwbec5pfkpfslaxbdae" style="color: black;">Genome Research</a> </i> &nbsp;
Understanding the changes in diverse molecular pathways underlying the development of breast tumors is critical for improving diagnosis, treatment, and drug development. Here, we used RNA-profiling of canine mammary tumors (CMTs) coupled with a robust analysis framework to model molecular changes in human breast cancer. Our study leveraged a key advantage of the canine model, the frequent presence of multiple naturally occurring tumors at diagnosis, thus providing samples spanning normal
more &raquo; ... benign and malignant tumors from each patient. We demonstrated human breast cancer signals, at both expression and mutation level, are evident in CMTs. Profiling multiple tumors per patient enabled by the CMT model allowed us to resolve statistically robust transcription patterns and biological pathways specific to malignant tumors versus those arising in benign tumors or shared with normal tissues. We demonstrated that multiple-histological-samples per patient is necessary to effectively capture these progression-related signatures, and that carcinoma-specific signatures are predictive of survival for human breast cancer patients. To catalyze and support similar analyses and use of the CMT model by other biomedical researchers, we provide FREYA, a robust data processing pipeline and statistical analyses framework.
<span class="external-identifiers"> <a target="_blank" rel="external noopener noreferrer" href="https://doi.org/10.1101/gr.256388.119">doi:10.1101/gr.256388.119</a> <a target="_blank" rel="external noopener" href="https://www.ncbi.nlm.nih.gov/pubmed/33361113">pmid:33361113</a> <a target="_blank" rel="external noopener" href="https://pubmed.ncbi.nlm.nih.gov/PMC7849403/">pmcid:PMC7849403</a> <a target="_blank" rel="external noopener" href="https://fatcat.wiki/release/kfqs63crwzedbny6fdfdkh3yti">fatcat:kfqs63crwzedbny6fdfdkh3yti</a> </span>
<a target="_blank" rel="noopener" href="https://web.archive.org/web/20210716102508/https://genome.cshlp.org/content/31/2/337.full.pdf" title="fulltext PDF download" data-goatcounter-click="serp-fulltext" data-goatcounter-title="serp-fulltext"> <button class="ui simple right pointing dropdown compact black labeled icon button serp-button"> <i class="icon ia-icon"></i> Web Archive [PDF] <div class="menu fulltext-thumbnail"> <img src="https://blobs.fatcat.wiki/thumbnail/pdf/99/32/99326af6448d648d4984ebbc54fcc6a1bff0b1cb.180px.jpg" alt="fulltext thumbnail" loading="lazy"> </div> </button> </a> <a target="_blank" rel="external noopener noreferrer" href="https://doi.org/10.1101/gr.256388.119"> <button class="ui left aligned compact blue labeled icon button serp-button"> <i class="external alternate icon"></i> Publisher / doi.org </button> </a> <a target="_blank" rel="external noopener" href="https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7849403" title="pubmed link"> <button class="ui compact blue labeled icon button serp-button"> <i class="file alternate outline icon"></i> pubmed.gov </button> </a>
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