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TF-centered downstream gene set enrichment analysis: Inference of causal regulators by integrating TF-DNA interactions and protein post-translational modifications information

Qi Liu, Yejun Tan, Tao Huang, Guohui Ding, Zhidong Tu, Lei Liu, Yixue Li, Hongyue Dai, Lu Xie
2010 BMC Bioinformatics  
We constructed hierarchical and multi-layer regulation models to derive possible downstream gene sets of a TF using not only TF-DNA interactions, but also, for the first time, post-translational modifications  ...  Results: We developed a TF-centered downstream gene set enrichment analysis approach to identify potential causal regulators responsible for expression changes.  ...  The downstream gene sets of each TF were derived by integrating TF-DNA interactions and post-translational modifications (PTM) information.  ... 
doi:10.1186/1471-2105-11-s11-s5 pmid:21172055 pmcid:PMC3024863 fatcat:uc7ata2dczgsnhvxlar5qml5ia

Multiscale Analysis of Independent Alzheimer's Cohorts Finds Disruption of Molecular, Genetic, and Clinical Networks by Human Herpesvirus

Ben Readhead, Jean-Vianney Haure-Mirande, Cory C. Funk, Matthew A. Richards, Paul Shannon, Vahram Haroutunian, Mary Sano, Winnie S. Liang, Noam D. Beckmann, Nathan D. Price, Eric M. Reiman, Eric E. Schadt (+3 others)
2018 Neuron  
We constructed multiscale networks of the late-onset AD-associated virome, integrating genomic, transcriptomic, proteomic, and histopathological data across four brain regions from human post-mortem tissue  ...  We observed regulatory relationships linking viral abundance and modulators of APP metabolism, including induction of APBB2, APPBP2, BIN1, BACE1, CLU, PICALM, and PSEN1 by HHV-6A.  ...  Kinase enrichment analysis of candidate virus-TF associations were performed as described in "Molecular and functional enrichment analysis", while subsetting the gene background to the set of 569 TF within  ... 
doi:10.1016/j.neuron.2018.05.023 pmid:29937276 pmcid:PMC6551233 fatcat:td24marnojev3i6iooageqtggi

Multiomics analysis reveals extensive epigenome remodeling during cortical development [article]

Florian Noack, Silvia Vangelisti, Madalena Carido, Faye Chong, Boyan Bonev
2020 bioRxiv   pre-print
Our analysis identifies thousands of novel enhancer-gene pairs associated with dynamic changes in chromatin accessibility and gene expression along the differentiation trajectory.  ...  Applying an integrative multiomics approach, e.g. combining single-cell RNA-seq, single-cell ATAC-seq together with cell-type-specific DNA methylation and 3D genome measurements, we systematically map  ...  Collectively, these results highlight how integrating scRNA and scATAC and utilizing correlated enhancer-gene pairs can be used to successfully infer GRNs downstream of TFs, even in the absence of ChIP-seq  ... 
doi:10.1101/2020.08.07.241828 fatcat:vyuauhgq5ffufkg34yeq6nhw2y

Network analysis identifies regulators of lineage-specific phenotypes in Mycobacterium tuberculosis [article]

Amir Banaei-Esfahani, Andrej Trauner, Sonia Borrell Farnov, Sebastian M. Gygli, Tige R. Rustad, Julia Feldmann, Ludovic C. Gillet, Olga T. Schubert, David R. Sherman, Christian Beisel, Sebastien Gagneux, Ruedi Aebersold (+1 others)
2020 bioRxiv   pre-print
Our data revealed different degrees of correlation between transcript and protein abundances across clinical strains and functional gene categories, indicating variable levels of post-transcriptional regulation  ...  Contrasting genomic and gene expression data showed that the magnitude of the transcriptional and translational changes was proportional to the phylogenetic distance between strains, with one out of three  ...  We would also thank the Scientific IT Support (ID SIS) of ETH Zurich and the scientific computing center at University of Basel for support and maintenance of the laboratory-internal computing infrastructure  ... 
doi:10.1101/2020.02.14.943365 fatcat:skcjeon75ncihhgwxwbjk5xwfu

Integrated Inference and Analysis of Regulatory Networks from Multi-Level Measurements [chapter]

Christopher S. Poultney, Alex Greenfield, Richard Bonneau
2012 Methods in Cell Biology  
models for the control of the co-regulated groups from the biclustering step; and a visualization and analysis step, designed to find and communicate key features of the network.  ...  Learning biological networks from even the most complete data sets is challenging; we argue that integrating new data types into the inference pipeline produces networks of increased accuracy, validity  ...  The mediators of these effects are transcription factors (TFs), which are proteins that bind the DNA and modulate the transcript abundance of their downstream targets, and environmental factors (EFs),  ... 
doi:10.1016/b978-0-12-388403-9.00002-3 pmid:22482944 pmcid:PMC5615108 fatcat:p2bycgc4a5e7xixoqwy2nudzd4

APG: an Active Protein-Gene Network Model to Quantify Regulatory Signals in Complex Biological Systems

Jiguang Wang, Yidan Sun, Si Zheng, Xiang-Sun Zhang, Huarong Zhou, Luonan Chen
2013 Scientific Reports  
Firstly, we theoretically and computationally demonstrate the effectiveness of APG by comparing with the traditional strategy based only on TF downstream-regulation information.  ...  TF upstream-regulation and downstream-regulation high-throughput data.  ...  Acknowledgement We thank Katsuhisa Horimoto and Qianfei Wang for critical reading and suggestions.  ... 
doi:10.1038/srep01097 pmid:23346354 pmcid:PMC3549541 fatcat:qlpddiyzjbb53kpgosq6k5ohay

Genomic and regulatory characteristics of significant transcription factors in colorectal cancer metastasis

Bin Zhou, Rui Guo
2018 Scientific Reports  
Finally, we inferred the associations between the target genes by Bayesian networks and identified LMO7 and ARL8A as potential clinical biomarkers.  ...  Besides that, rely on the ATAC-Seq and ChIP-Seq profiles, we detected the target genes regulated by each transcription factor in the active chromatin zones.  ...  Data Availability The clinical information, RNA-Seq profiles, copy number variation files, DNA methylation files analyzed during the current study are available in [  ... 
doi:10.1038/s41598-018-36168-8 pmid:30546056 pmcid:PMC6292939 fatcat:aqhj6gg72vhkxj3nxxushy3ysq

An integrated multi-omic analysis of iPSC-derived motor neurons from C9ORF72 ALS patients [article]

The NeuroLINCS Consortium, Loren Ornelas, Emilda Gomez, Lindsay Panther, Aaron Frank, Susan Lei, Berhan Mandefro, Maria G Banuelos, Brandon Shelley, Julia A Kaye, Leandro Lima, Stacia Wyman (+35 others)
2020 bioRxiv   pre-print
of the relationship between DNA, RNA, epigenetics and protein in the same pool of tissue.  ...  However, a number of the core dysregulated pathways remained significant using the integrated multiomic analysis.  ...  We also acknowledge and thank the Target ALS Postmortem Tissue Core for their contribution of samples and data.  ... 
doi:10.1101/2020.11.01.362269 fatcat:6p3kludh2zahpj5nemdqi4rqke

Systems biology analysis reveals NFAT5 as a novel biomarker and master regulator of inflammatory breast cancer

Andrea Remo, Ines Simeone, Massimo Pancione, Pietro Parcesepe, Pascal Finetti, Luigi Cerulo, Halima Bensmail, Daniel Birnbaum, Steven J Van Laere, Vittorio Colantuoni, Franco Bonetti, François Bertucci (+2 others)
2015 Journal of Translational Medicine  
Pathway enrichment analysis was used to characterize predicted targets of candidate genes.  ...  Methods: In-silico modeling and Algorithm for the Reconstruction of Accurate Cellular Networks (ARACNe) on IBC/ non-IBC (nIBC) gene expression data (n = 197) was employed to identify novel master regulators  ...  The transcriptional activity of NFATs is primarily regulated by post-translational modifications that in turn determine the subcellular localization.  ... 
doi:10.1186/s12967-015-0492-2 pmid:25928084 pmcid:PMC4438533 fatcat:taxoedgkwvd2vfewzcodzgicau

A Pan-Cancer Analysis of Enhancer Expression in Nearly 9000 Patient Samples

Han Chen, Chunyan Li, Xinxin Peng, Zhicheng Zhou, John N. Weinstein, Han Liang, Samantha J. Caesar-Johnson, John A. Demchok, Ina Felau, Melpomeni Kasapi, Martin L. Ferguson, Carolyn M. Hutter (+719 others)
2018 Cell  
A computational method that infers causal enhancer-targetgene relationships d Enhancers as key regulators of therapeutic targets, including PD-L1  ...  Graphical Abstract Highlights d Systematic analysis of enhancer expression across 9,000 samples of 33 cancer types d Global enhancer activation positively correlates with aneuploidy but not mutations d  ...  The plasmids with upstream and downstream sgRNAs were mixed and then transfected using lipofectamine 3000 into the human embryonic kidney (HEK) 293T cell line grown in Dulbecco's modification of Eagle's  ... 
doi:10.1016/j.cell.2018.03.027 pmid:29625054 pmcid:PMC5890960 fatcat:fxvqzmbptfe2toh43pkxlysfgy

Integration of pan-cancer transcriptomics with RPPA proteomics reveals mechanisms of epithelial-mesenchymal transition

Simon Koplev, Katie Lin, Anders B. Dohlman, Avi Ma'ayan, Julio Saez-Rodriguez
2018 PLoS Computational Biology  
By querying gene expression signatures collected from cancer cell lines after small-molecule perturbations, we identify enrichment for histone deacetylase (HDAC) inhibitors as inducers of EMT, and kinase  ...  In conclusion, integrative analysis of pan-cancer proteomic and transcriptomic data reveals key regulatory mechanisms of oncogenic transformation.  ...  Acknowledgments We would like to give special thanks to Professor Gordon Mills from MD Anderson Cancer Center who shared the RPPA data prior to its publication, and also provided us with useful comments  ... 
doi:10.1371/journal.pcbi.1005911 pmid:29293502 pmcid:PMC5766255 fatcat:5b6lhlrpo5empdtsut5wkoqchu

Global analysis of epigenetic heterogeneity identifies divergent drivers of esophageal squamous cell carcinoma [article]

WEI CAO, Hayan Lee, Wei Wu, Aubhishek Zaman, Sean McCorkle, Ming Yan, Justin Chen, Qinghe Xing, Nasa Sinnott-Armstrong, Hongen Xu, M.Reza Sailani, Wenxue Tang (+18 others)
2019 bioRxiv   pre-print
Gene body methylation, polycomb repressive complex occupancy, and CTCF binding sites associate with cancer-specific gene regulation.  ...  Gene-specific cancer driver roles of epigenetic alterations and heterogeneity are identified.  ...  Acknowledgements This study was supported by the National Natural Science Foundation of China (Grants 81171992,  ... 
doi:10.1101/641357 fatcat:yueijf5iybgpva3sclb6qcvxpu

Chromatin accessibility profiling methods

Liesbeth Minnoye, Georgi K. Marinov, Thomas Krausgruber, Lixia Pan, Alexandre P. Marand, Stefano Secchia, William J. Greenleaf, Eileen E. M. Furlong, Keji Zhao, Robert J. Schmitz, Christoph Bock, Stein Aerts
2021 Nature Reviews Methods Primers  
These post-translational modifications are often correlated with chromatin accessibility and can reflect specific functionalities of genomic regions related to the regulation of gene expression 11, 12  ...  Changes in these post-translational modifications, such as increased or decreased histone methylation and acetylation, are affected by a large set of chromatin-modifying enzymes that can be recruited to  ...  Acknowledgements This work was supported by the Division of Intramural Research, National Heart, Lung and Blood Institute, National Institutes of Health (NIH) (K.Z.) and the National Science Foundation  ... 
doi:10.1038/s43586-020-00008-9 fatcat:cohn4r55uvb5hpxklzn7qv2qg4

The Emerging Potential for Network Analysis to Inform Precision Cancer Medicine

Kivilcim Ozturk, Michelle Dow, Daniel E. Carlin, Rafael Bejar, Hannah Carter
2018 Journal of Molecular Biology  
However biological systems are complex, and patients may differ not only by the specific genetic alterations in their tumor, but by more subtle interactions among such alterations.  ...  Here we discuss applications of network analysis to study tumor biology, early methods for N-of-1 tumor genome analysis and the path for such tools to the clinic.  ...  Acknowledgments This work was supported by the National Institutes of Health (NIH) grant DP5-OD017937 to H.C., SDCSB Systems Biology training grant (GM085764 and CA209891) to K.O., National Library of  ... 
doi:10.1016/j.jmb.2018.06.016 pmid:29908887 pmcid:PMC6097914 fatcat:x2jgrae22be4bfzgc4nh46mwni

Reverse Engineering: A Key Component of Systems Biology to Unravel Global Abiotic Stress Cross-Talk

Swetlana Friedel, Björn Usadel, Nicolaus von Wirén, Nese Sreenivasulu
2012 Frontiers in Plant Science  
We further propose to combine information on gene-by-gene interactions with data from physical interaction platforms such as protein-protein or TF-gene networks.  ...  To explore the full potential of gene network inference in the area of abiotic stress tolerance, we need to validate hypotheses by implementing time-dependent gene expression data from genetically engineered  ...  Types of interactions in MetNetDB include transcription, translation, protein modification, assembly, allosteric regulation, translocation from one subcellular compartment to another.  ... 
doi:10.3389/fpls.2012.00294 pmid:23293646 pmcid:PMC3533172 fatcat:hhqvotht6jdnbpuwayxljdd5ya
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