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Causal Modeling Using Network Ensemble Simulations of Genetic and Gene Expression Data Predicts Genes Involved in Rheumatoid Arthritis

Heming Xing, Paul D. McDonagh, Jadwiga Bienkowska, Tanya Cashorali, Karl Runge, Robert E. Miller, Dave DeCaprio, Bruce Church, Ronenn Roubenoff, Iya G. Khalil, John Carulli, Edmund J. Crampin
2011 PLoS Computational Biology  
We describe a data analysis strategy for predicting gene expression measures that are critical for rheumatoid arthritis using a combination of comprehensive genotyping, whole blood gene expression profiles  ...  In silico simulations of targeted, personalized perturbations of gene expression measures from both network ensembles identify transcripts in three broad categories.  ...  Gregesen and the Autoimmune Biomarkers Collaborative Network (ABCoN) collaborating investigators for access to the ABCoN dataset.  ... 
doi:10.1371/journal.pcbi.1001105 pmid:21423713 pmcid:PMC3053315 fatcat:nesper5zbnci7hrwa4f2vsp5ei

Pathway-Based Kernel Boosting for the Analysis of Genome-Wide Association Studies

Stefanie Friedrichs, Juliane Manitz, Patricia Burger, Christopher I. Amos, Angela Risch, Jenny Chang-Claude, Heinz-Erich Wichmann, Thomas Kneib, Heike Bickeböller, Benjamin Hofner
2017 Computational and Mathematical Methods in Medicine  
Applications to GWAS data on rheumatoid arthritis and lung cancer resulted in sparse models which were based on pathways interpretable in a clinical sense.  ...  Thus, kernel boosting constitutes a new, powerful tool in the analysis of GWAS data and towards the understanding of biological processes involved in disease susceptibility.  ...  The rheumatoid arthritis data considered in this article were provided by the National Institutes of Health (Grant AR44422). The analyzed lung cancer study was made available through TRICL Grant no.  ... 
doi:10.1155/2017/6742763 pmid:28785300 pmcid:PMC5530424 fatcat:cgfcskkjc5honnidp2xmxqvfwe

Discovery of Emphysema Relevant Molecular Networks from an A/J Mouse Inhalation Study Using Reverse Engineering and Forward Simulation (REFS™)

Yang Xiang, Ulrike Kogel, Stephan Gebel, Michael J. Peck, Manuel C. Peitsch, Viatcheslav R. Akmaev, Julia Hoeng
2014 Gene Regulation and Systems Biology  
An ensemble of molecular networks was generated using refS™, and simulations showed that it could successfully recover the measured experimental data for gene expression and COPD-relevant endpoints.  ...  The ensemble of networks was then employed to simulate thousands of in silico gene knockdown experiments.  ...  Acknowledgments We are grateful to Sam Ansari for submitting the gene expression data to Arrayexpress (e-MTAB-1426).  ... 
doi:10.4137/grsb.s13140 pmid:24596455 pmcid:PMC3937248 fatcat:pt7tcxfnu5fhjehl6nczevdqhy

Gene and Gene-Set Analysis for Genome-Wide Association Studies [article]

Inti Pedroso
2013 arXiv   pre-print
and gene-set analyses of GWAS data; c) mine GWAS of neuropsychiatric disorders using gene, gene-sets and integrative biology analyses with gene-expression studies; and d) explore the ability of these  ...  The project aimed to a) implement and develop new gene-based methods to derive gene-level statistics to use GWAS in well established system biology tools; b) use of these gene-level statistics in networks  ...  In these studies the causal network was a co-expression network highly enriched with genes that have a causal or driver role on metabolic traits.  ... 
arXiv:1308.4102v1 fatcat:plmjweiqrbggljkf3kxwvd4ify

Whole exome sequencing of a Saudi family and Systems Biology Analysis identifies CPED1 as a Putative Causative gene to Celiac Disease

Hifaa A. Bokhari, Noor A. Shaik, Babajan Banganapalli, Khalidah K. Nasser, Hossain Ibrahim Ageel, Ali Saad Al Shamrani, Omran M. Rashidi, Omar Yaseen Al Ghubayshi, Jilani Shaik, Aftab Ahmed, Nuha Mohammad Alrayes, Jumana Y. Al-Aama (+2 others)
2020 Saudi Journal of Biological Sciences  
Genotype-Tissue Expression (GTEx) data has revealed that CPED1 is abundantly expressed in gastrointestinal mucosa.  ...  The cell culture and animal model studies could provide further insight into the exact role of CPED1 p.Thr81Ala variant in the pathophysiology of CD.  ...  Overall, our results show a similar correlation that links CPED1 as a CD causal gene based on the genome wide association studies in UKBB with inflammatory bowel disease, rheumatoid arthritis and multiple  ... 
doi:10.1016/j.sjbs.2020.04.011 pmid:32489286 pmcid:PMC7254030 fatcat:vcyfacm7yfdcpki32ptngm46ky

Proteins Encoded in Genomic Regions Associated with Immune-Mediated Disease Physically Interact and Suggest Underlying Biology

Elizabeth J. Rossin, Kasper Lage, Soumya Raychaudhuri, Ramnik J. Xavier, Diana Tatar, Yair Benita, Chris Cotsapas, Mark J. Daly, Takashi Gojobori
2011 PLoS Genetics  
Using sets of loci defined in rheumatoid arthritis (RA) and Crohn's disease (CD) GWAS, we build protein-protein interaction (PPI) networks for genes within associated loci and find abundant physical interactions  ...  Furthermore, we show that the RA and CD networks have predictive power by demonstrating that proteins in these networks, not encoded in the confirmed list of disease associated loci, are significantly  ...  The Inflammatory Bowel Disease Genetics Consortium consists of the following people: Andre Franke 1 , Dermot P.B. McGovern 2,14 , Jeffrey C. Barrett  ... 
doi:10.1371/journal.pgen.1001273 pmid:21249183 pmcid:PMC3020935 fatcat:yjwrpekmhbfvpjnx3n3u46rjo4

Exome Sequencing Identifies the Extremely Rare ITGAV and FN1 Variants in Early Onset Inflammatory Bowel Disease Patients

Huda Husain Al-Numan, Rana Mohammed Jan, Najla bint Saud Al-Saud, Omran M. Rashidi, Nuha Mohammad Alrayes, Hadeel A. Alsufyani, Abdulrahman Mujalli, Noor Ahmad Shaik, Mahmoud Hisham Mosli, Ramu Elango, Omar I. Saadah, Babajan Banaganapalli
2022 Frontiers in Pediatrics  
Data from knockout mouse models for ITGAV gene has revealed that the dysregulated expression of this gene impacts intestinal immune homeostasis.  ...  Functional biology data suggested that both genes show abundant expression in gastrointestinal tract and immune organs, involved in immune cell restriction, regulation of different immune related pathways  ...  The authors would also extend their sincere thanks to 'Saudi Ajal for Health Services for their help in data analysis and presentation of our study results.  ... 
doi:10.3389/fped.2022.895074 pmid:35692981 pmcid:PMC9178107 fatcat:4jthjpvj2zamvmwp4ruax6njqi

46th European Mathematical Genetics Meeting (EMGM) 2018, Cagliari, Italy, April 18-20, 2018: Abstracts

2018 Human Heredity  
Studies have shown extensive migration and gene flow among European populations. We will focus on elucidation of ancient and  ...  We assume a genetic background contributing to a lower CVD mortality in resettlers and a healthy migrant effect for the ancestors of the resettlers migrating to the FSU.  ...  Our findings unravel tissue-specific, causal gene-expression networks shared among a range of phenotypes.  ... 
doi:10.1159/000488519 pmid:29669356 fatcat:wqy2xcswtngm3kw2oc4k7xglf4

The genetic architecture of osteoarthritis: insights from UK Biobank [article]

Eleni Zengini, Konstantinos Hatzikotoulas, Ioanna Tachmazidou, Julia Steinberg, Fernando P. Hartwig, Lorraine Southam, Sophie Hackinger, Cindy G. Boer, Unnur Styrkarsdottir, Daniel Suveges, Britt Kilian, Arthur Gilly (+11 others)
2017 bioRxiv   pre-print
Following replication and meta-analysis in up to 30,727 cases and 297,191 controls, we report 9 new osteoarthritis loci, in all of which the most likely causal variant is non-coding.  ...  For three loci, we detect association with biologically-relevant radiographic endophenotypes, and in five signals we identify genes that are differentially expressed in degraded compared to intact articular  ...  We are grateful to Roger Brooks, Jyoti Choudhary and Theodoros Roumeliotis for their contribution to the functional genomics data collection.  ... 
doi:10.1101/174755 fatcat:hknfyclzcvcnbemjykyohsrl5q

Integrative Omics for Informed Drug Repurposing: Targeting CNS Disorders [article]

Rammohan Shukla, Nicholas Henkel, Khaled Alganem, Abdul-rizaq Hamoud, James Reigle, Rawan S Alnafisah, Hunter M Eby, Ali S Imami, Justin Creeden, Scott A Miruzzi, Jaroslaw Meller, Robert E Mccullumsmith
2020 bioRxiv   pre-print
This is likely due to regulatory challenges involving the high cost and slow-pace of drug development for CNS disorders as well as due to limited understanding of disease causality.  ...  Historically, empirical drug-repurposing is a standard practice in psychiatry; however, recent advances in characterizing molecules with their structural and transcriptomic signatures along with ensemble  ...  This may be due to lack of animal models for the disease in question or poor simulation of disease in the animal model.  ... 
doi:10.1101/2020.04.24.060392 fatcat:af7hldmvmjeulagxjvbamai2ya

Crowdsourcing biomedical research: leveraging communities as innovation engines

Julio Saez-Rodriguez, James C. Costello, Stephen H. Friend, Michael R. Kellen, Lara Mangravite, Pablo Meyer, Thea Norman, Gustavo Stolovitzky
2016 Nature reviews genetics  
Crowdsourcing the analysis of complex and massive data has emerged as a framework to find robust methodologies.  ...  The generation of large-scale biomedical data is creating unprecedented opportunities for basic and translational science.  ...  The authors also thank the DREAM Challenges community, who taught them everything about Challenges that they have tried to share in this Review.  ... 
doi:10.1038/nrg.2016.69 pmid:27418159 pmcid:PMC5918684 fatcat:tap77ocblrbydl3fc6connsnwi

A Bayesian mathematical model of motor and cognitive outcomes in Parkinson's disease

Boris Hayete, Diane Wuest, Jason Laramie, Paul McDonagh, Bruce Church, Shirley Eberly, Anthony Lang, Kenneth Marek, Karl Runge, Ira Shoulson, Andrew Singleton, Caroline Tanner (+4 others)
2017 PLoS ONE  
Machine learning dynamic Bayesian graphical models were used to identify and simulate predictors and outcomes.  ...  Analyses were conducted in 244 participants with complete demographic, clinical, genetic, and dopamine transporter imaging data.  ...  Acknowledgments The authors would like to thank Jadwiga Bienkowska, Tao Song, and Matt Wien for their related analyses and data transfer activities at Biogen, and David Oakes at the University of Rochester  ... 
doi:10.1371/journal.pone.0178982 pmid:28604798 pmcid:PMC5467836 fatcat:my6bhslqjfh2lmwibfpbeeiihy

Whole genome sequencing analysis of the cardiometabolic proteome

Arthur Gilly, Young-Chan Park, Grace Png, Thea Bjornland, Lorraine Southam, Daniel Suveges, Sonja Neumeyer, Iris Fischer, Andrei Barysenka, N. William Rayner, Emmanouil Tsafantakis, Maria Karaleftheri (+2 others)
2019 biorxiv/medrxiv  
We construct and validate polygenic risk scores that explain up to 45% of protein level variation, and find significant correlation between genetically-predicted biomarker levels and cardiovascular disease  ...  We identify replicating evidence for rare-variant -acting protein quantitative trait loci for five genes, involving both coding and non-coding variation.  ...  The GATK3 program was made available through the generosity of the Medical and Population Genetics program at the Broad Institute, Inc.  ... 
doi:10.1101/854752 fatcat:h6qq65njuzghzicxoehfj23ti4

Systems Toxicology: From Basic Research to Risk Assessment

Shana J. Sturla, Alan R. Boobis, Rex E. FitzGerald, Julia Hoeng, Robert J. Kavlock, Kristin Schirmer, Maurice Whelan, Martin F. Wilks, Manuel C. Peitsch
2014 Chemical Research in Toxicology  
The integrated data analysis leads to the identification of how biological networks are perturbed by the exposure and enables the development of predictive mathematical models of toxicological processes  ...  In Systems Toxicology, quantitative systems-wide molecular changes in the context of an exposure are measured, and a causal chain of molecular events linking exposures with adverse outcomes (i.e., functional  ...  Notes The views expressed in this article are those of the author(s) and do not necessarily represent the views or policies of the U.S. Environmental Protection Agency.  ... 
doi:10.1021/tx400410s pmid:24446777 pmcid:PMC3964730 fatcat:fulgun73cjdgxk4iitavahcwvm

Programme Booklet Of The 11Th Iscb Student Council Symposium, Dublin, 2015 [article]

Mehedi Hassan, R Gonzalo Parra
2015 Zenodo  
This is a booklet containing programme of the day of the 11th ISCB Student Council Symposium, Dublin, 10 July 2015. This also contains all the abstracts of works presented on the day.  ...  For example, eFORGE enrichments were found in CD56+ cells and thymus tissue in an EWAS for rheumatoid arthritis, and CD4+ cells in an EWAS for multiple sclerosis.  ...  Recent findings, including ours on mammalian causal GRNs, showed that it is virtually impossible to infer causal GRNs in eukaryotes without using gene perturbation data.  ... 
doi:10.5281/zenodo.1253018 fatcat:b75h2xdwmralzfqdhs6jd6k4vm
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