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Uncovering Effective Explanations for Interactive Genomic Data Analysis

Silu Huang, Charles Blatti, Saurabh Sinha, Aditya Parameswaran
2020 Patterns  
Better tools are needed to enable researchers to quickly identify and explore effective and interpretable feature-based explanations for discriminating multi-class genomic datasets, e.g., healthy versus  ...  With its generalizable optimizations and framework, GENVISAGE opens up real-time feature-based explanation generation to data from massive sequencing efforts, as well as many other scientific domains.  ...  ACKNOWLEDGMENTS The authors gratefully acknowledge funding support for this work from the Na- DECLARATION OF INTERESTS The authors declare no competing interests.  ... 
doi:10.1016/j.patter.2020.100093 pmid:33205133 pmcid:PMC7660438 fatcat:nwyywzog4nbqjnne46a6f53ote

Understanding Genotype-Phenotype Effects in Cancer via Network Approaches

Yoo-Ah Kim, Dong-Yeon Cho, Teresa M. Przytycka, Rachel Karchin
2016 PLoS Computational Biology  
Indeed, network-centric approaches have proven to be helpful for finding genotypic causes of diseases, classifying disease subtypes, and identifying drug targets.  ...  In this review, we discuss how networks can be used to help understand patientto-patient variations and how one can leverage this variability to elucidate interactions between cancer drivers.  ...  Illustrations of how gene networks can be used in cancer data analysis.  ... 
doi:10.1371/journal.pcbi.1004747 pmid:26963104 pmcid:PMC4786343 fatcat:p2zqfax3gfag7jutp3tq52tqve

dcVar: a method for identifying common variants that modulate differential correlation structures in gene expression data

Caleb A. Lareau, Bill C. White, Courtney G. Montgomery, Brett A. McKinney
2015 Frontiers in Genetics  
We apply dcVar to the HapMap3 eQTL dataset and demonstrate the utility of this methodology at uncovering novel function of variants of interest with examples from a height genome-wide association and cancer  ...  Recent studies have implicated the role of differential co-expression or correlation structure in gene expression data to help explain phenotypic differences.  ...  Our implementation of a framework to compute differential correlation from variants in C++ provides a tool for researchers to uncover these effects in a genome-wide eQTL or RNA-Seq analysis.  ... 
doi:10.3389/fgene.2015.00312 pmid:26539209 pmcid:PMC4609883 fatcat:n6b6lmy43vgyvfk5opqbgydfmq

Perspective on the genetics of attention deficit/hyperactivity disorder

Benjamin M. Neale, Stephen V. Faraone
2008 American Journal of Medical Genetics Part B: Neuropsychiatric Genetics  
One hope for genetic studies is the potential for the discovery of new biological pathways and new targets for treatment.  ...  This set of articles recapitulates the major trends in the field of complex psychiatric genetics, underscoring how genetic studies of ADHD have evolved, and what approaches are needed to uncover the genetic  ...  None of the SNPs tested achieved genome-wide significance on the main effect of the moderator or the test for the interaction between the moderator and ADHD diagnosis.  ... 
doi:10.1002/ajmg.b.30875 pmid:18951432 fatcat:w2jkxzopczgkpayohg3vm64koi

Learning to swim in a sea of genomic data

Ekta Khurana
2013 Genome Biology  
Acknowledgements The author thanks Chris Tyler-Smith (Wellcome Trust Sanger Institute, UK), Jieming Chen and Suganthi Balasubramanian (Yale University, USA) for comments and suggestions.  ...  These talks highlighted the importance of integrating functional genomics studies with whole-genome sequencing data to uncover the effects of sequence variants.  ...  A likely explanation for this observation is that dominant mutations tend to be gain-offunction and mostly cause the gain of different functions in interacting proteins, as opposed to recessive mutations  ... 
doi:10.1186/gb4144 pmid:24314026 pmcid:PMC4053704 fatcat:72nxemflxzgr5kyx4c2y5pmrp4

Toward the dynamic interactome: it's about time

T. M. Przytycka, M. Singh, D. K. Slonim
2010 Briefings in Bioinformatics  
conditions, is increasingly helpful in elucidating interaction dynamics.  ...  Dynamic molecular interactions play a central role in regulating the functioning of cells and organisms.  ...  We thank her for many illuminating discussions, and the organizers of the PSB conference for supporting our session.  ... 
doi:10.1093/bib/bbp057 pmid:20061351 pmcid:PMC2810115 fatcat:xbj7ugs6nbed7guys2ie5z3efa

Pathway-based classification of genetic diseases

Ivan Y. Iourov, Svetlana G. Vorsanova, Yuri B. Yurov
2019 Molecular Cytogenetics  
However, recent achievements in systems biology have offered a possibility to explore the consequences of a genetic defect from genomic variations to molecular/cellular pathway alterations unique to a  ...  The basic idea of our classification is to propose pathways as parameters for designating a genetic disease.  ...  Focusing on uncovering underlying disease mechanisms using high-resolution genomic data, pathway-based analysis has provided numerous discoveries in the field of molecular medicine.  ... 
doi:10.1186/s13039-019-0418-4 pmid:30766616 pmcid:PMC6362588 fatcat:csahwgl3rfhqvox7zungdlkgdq

Identification and characterization of DNA sequences that prevent glucocorticoid receptor binding to nearby response elements

Jonas Telorac, Sergey V. Prykhozhij, Stefanie Schöne, David Meierhofer, Sascha Sauer, Morgane Thomas-Chollier, Sebastiaan H. Meijsing
2016 Nucleic Acids Research  
Motif analyses uncovered candidate Negative Regulatory Sequences (NRSs) that interfere with genomic GR binding.  ...  Instead, we find that NRSs interact with proteins found at sub-nuclear structures called paraspeckles and that these proteins might mediate the repressive effects of NRSs.  ...  Thus, one explanation for the effect of NRSs could be that they render nearby genomic regions inaccessible.  ... 
doi:10.1093/nar/gkw203 pmid:27016732 pmcid:PMC5291246 fatcat:mpaex2heofcidbfwtlt3qhkrpy

Reworking GWAS Data to Understand the Role of Nongenetic Factors in MS Etiopathogenesis

Mechelli, Umeton, Manfrè, Romano, Buscarinu, Rinaldi, Bellucci, Bigi, Ferraldeschi, Salvetti, Ristori
2020 Genes  
We then surveyed studies on the bioinformatic reworking of genome-wide association studies (GWAS) data, with aggregate analyses of many GWAS loci, each contributing with a small effect to the overall disease  ...  This complexity poses at least two challenges: the definition of an etiological model including the impact of nongenetic factors, and the clinical translation of genomic data that may be drivers for new  ...  which are known to interact with the genetic signals resulting from genome-scale data.  ... 
doi:10.3390/genes11010097 pmid:31947683 pmcid:PMC7017269 fatcat:l62b4ntdn5cazpp3m23mvektji

Highly polygenic architecture of antidepressant treatment response: Comparative analysis of SSRI and NRI treatment in an animal model of depression

Karim Malki, Maria Grazia Tosto, Héctor Mouriño-Talín, Sabela Rodríguez-Lorenzo, Oliver Pain, Irfan Jumhaboy, Tina Liu, Panos Parpas, Stuart Newman, Artem Malykh, Lucia Carboni, Rudolf Uher (+4 others)
2016 American Journal of Medical Genetics Part B: Neuropsychiatric Genetics  
Highly Polygenic Architecture of Antidepressant Treatment Response: Comparative Analysis of SSRI and NRI Treatment in an Animal Model of Depression. Am J Med Genet Part B 9999:1-16.  ...  ACKNOWLEDGMENTS The Genome-Based Therapeutic Drugs for Depression study was funded by a European Commission  ...  The same analysis was repeated for probe sets uncovered from the escitalopram versus saline classification analysis.  ... 
doi:10.1002/ajmg.b.32494 pmid:27696737 pmcid:PMC5434854 fatcat:pzvtelvifffg3nvubhgjb6o4bu

Computational solutions for omics data

Bonnie Berger, Jian Peng, Mona Singh
2013 Nature reviews genetics  
Finally, efficient means for storing, searching and retrieving data are of foremost concern as they are necessary for any analysis to proceed.  ...  Several software platforms and database systems have been developed for basic data analysis and integration 1-3 (BOX 1).  ...  Cowen for valuable feedback. B.B. thanks the US National Institutes of Health (NIH) for grant GM081871.  ... 
doi:10.1038/nrg3433 pmid:23594911 pmcid:PMC3966295 fatcat:b7n6xwzyc5gqzo7plgyoe257iq

Defining the genetic architecture of the predisposition to obesity: a challenging but not insurmountable task

Claude Bouchard
2009 American Journal of Clinical Nutrition  
However, a meta-analysis of 37 genome scan studies with data on 31,000 individuals from .10,000 families could not implicate unequivocally a single genetic locus for obesity or body mass index (BMI) (  ...  I see 2 possible avenues of explanation for this extraordinary discrepancy.  ... 
doi:10.3945/ajcn.2009.28933 pmid:19939981 fatcat:aq2leka22zaihdgs4cof7ob6x4

In the pursuit of complexity: Systems medicine in cancer biology

Edison T. Liu, Vladimir A. Kuznetsov, Lance D. Miller
2006 Cancer Cell  
This work shows that the intersect analysis of gene amplification and transcriptional expression on a genome-wide scale can uncover complex conditional interactions embedded in the systems map of transcriptional  ...  This work by Adler et al. highlights the fact that the intersection of two genome-wide scans (expression and chromosomal amplification) can yield interesting higher-order mechanistic explanations for biological  ... 
doi:10.1016/j.ccr.2006.03.026 pmid:16616330 fatcat:udnasembbzdynno5qkrayiq3ga

Expanding the uses of genome‐scale models with protein structures

Nathan Mih, Bernhard O Palsson
2019 Molecular Systems Biology  
In contrast, systems biology and genome-scale modeling have organically grown out of the wealth of data now being generated by diverse omics measurements.  ...  In this commentary, we highlight the challenges of integrating these two fields, with a focus on genome-scale metabolic modeling, and the novel findings that are made possible from such a merger.  ...  The authors graciously thank Marc Abrams for his help editing and proofreading this document. Conflict of interest The authors declare that they have no conflict of interest.  ... 
doi:10.15252/msb.20188601 pmid:31777175 pmcid:PMC6880182 fatcat:um26g7wm3bfojjcox5eie4f66y

Genome-wide analysis of interactions between ATP-dependent chromatin remodeling and histone modifications

Zhiming Dai, Xianhua Dai, Qian Xiang, Jihua Feng, Jiang Wang, Yangyang Deng, Caisheng He
2009 BMC Genomics  
Analysis of the genome-wide picture revealed that transcription-related modifications tend to interact with more chromatin remodelers.  ...  Our method succeeds in identifying known interactions and uncovers many previously unknown interactions between these two activities.  ...  Acknowledgements We thank Martin Kupiec for providing the chromatin modifier compendium and Euan Ashley for providing the Heatmap Builder.  ... 
doi:10.1186/1471-2164-10-304 pmid:19586523 pmcid:PMC2713269 fatcat:l6b37uif4femdd2cyeendqyun4
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