High-throughput data production technologies, particularly 'next-generation' DNA sequencing, have ushered in widespread and disruptive changes to biomedical research. Making sense of the large datasets produced by these technologies requires sophisticated statistical and computational methods , as well as substantial computational power. This has led to an acute crisis in life sciences, as researchers without informatics training attempt to perform computation-dependent analyses. Since 2005, the Galaxy project has worked to address this problem by providing a framework that makes advanced computational tools usable by non experts. Galaxy seeks to make data-intensive research more accessible , transparent and reproducible by providing a Web-based environment in which users can perform computational analyses and have all of the details automatically tracked for later inspection, publication , or reuse. In this report we highlight recently added features enabling biomedical analyses on a large scale.

The Galaxy platform for accessible, reproducible and collaborative biomedical analyses: 2016 update

Major depression is a debilitating psychiatric illness that is typically associated with low mood and anhedonia. Depression has a heritable component that has remained difficult to elucidate with current sample sizes due to the polygenic nature of the disorder. To maximize sample size, we meta-analyzed data on 807,553 individuals (246,363 cases and 561,190 controls) from the three largest genome-wide association studies of depression. We identified 102 independent variants, 269 genes, and 15 genesets associated with depression, including both genes and gene pathways associated with synaptic structure and neurotransmission. An enrichment analysis provided further evidence of the importance of prefrontal brain regions. In an independent replication sample of 1,306,354 individuals (414,055 cases and 892,299 controls), 87 of the 102 associated variants were significant after multiple testing correction. These findings advance our understanding of the complex genetic architecture of depression and provide several future avenues for understanding etiology and developing new treatment approaches.

https://www.pure.ed.ac.uk/ws/files/79772532/Meta_analysis_of_depression.pdf

Genome-wide meta-analysis of depression identifies 102 independent variants and highlights the importance of the prefrontal brain regions

The Biological General Repository for Interaction Datasets (BioGRID) is a public database that archives and disseminates genetic and protein
 interaction data from model organisms and humans
 (http://www.thebiogrid.org). BioGRID currently holds 347 966
 interactions (170 162 genetic, 177 804 protein) curated from both
 high-throughput data sets and individual focused studies, as derived
 from over 23 000 publications in the primary literature. Complete
 coverage of the entire literature is maintained for budding yeast
 (Saccharomyces cerevisiae), fission yeast (Schizosaccharomyces pombe)
 and thale cress (Arabidopsis thaliana), and efforts to expand curation
 across multiple metazoan species are underway. The BioGRID houses 48
 831 human protein interactions that have been curated from 10 247
 publications. Current curation drives are focused on particular areas
 of biology to enable insights into conserved networks and pathways that
 are relevant to human health. The BioGRID 3.0 web interface contains
 new search and display features that enable rapid queries across
 multiple data types and sources. An automated Interaction Management
 System (IMS) is used to prioritize, coordinate and track curation
 across international sites and projects. BioGRID provides interaction
 data to several model organism databases, resources such as Entrez-Gene
 and other interaction meta-databases. The entire BioGRID 3.0 data
 collection may be downloaded in multiple file formats, including PSI MI
 XML. Source code for BioGRID 3.0 is freely available without any
 restrictions.

/pdf/the-biogrid-interaction-database-2011-update-4t23jtqdsl.pdf

The BioGRID Interaction Database: 2011 update

The Biological General Repository for Interaction Datasets (BioGRID: https://thebiogrid.org) is an open access database dedicated to the annotation and archival of protein, genetic and chemical interactions for all major model organism species and humans. As of September 2016 (build 3.4.140), the BioGRID contains 1 072 173 genetic and protein interactions, and 38 559 post-translational modifications, as manually annotated from 48 114 publications. This dataset represents interaction records for 66 model organisms and represents a 30% increase compared to the previous 2015 BioGRID update. BioGRID curates the biomedical literature for major model organism species, including humans, with a recent emphasis on central biological processes and specific human diseases. To facilitate network-based approaches to drug discovery, BioGRID now incorporates 27 501 chemical-protein interactions for human drug targets, as drawn from the DrugBank database. A new dynamic interaction network viewer allows the easy navigation and filtering of all genetic and protein interaction data, as well as for bioactive compounds and their established targets. BioGRID data are directly downloadable without restriction in a variety of standardized formats and are freely distributed through partner model organism databases and meta-databases.

The BioGRID interaction database: 2017 update

Intratumor heterogeneity (ITH) drives neoplastic progression and therapeutic resistance. We used the bioinformatics tools 'expanding ploidy and allele frequency on nested subpopulations' (EXPANDS) and PyClone to detect clones that are present at a ≥10% frequency in 1,165 exome sequences from tumors in The Cancer Genome Atlas. 86% of tumors across 12 cancer types had at least two clones. ITH in the morphology of nuclei was associated with genetic ITH (Spearman's correlation coefficient, ρ = 0.24-0.41; P 2 clones coexisted in the same tumor sample (HR = 1.49, 95% CI: 1.20-1.87). In two independent data sets, copy-number alterations affecting either 75% of a tumor's genome predicted reduced risk (HR = 0.15, 95% CI: 0.08-0.29). Mortality risk also declined when >4 clones coexisted in the sample, suggesting a trade-off between the costs and benefits of genomic instability. ITH and genomic instability thus have the potential to be useful measures that can universally be applied to all cancers.

Pan-cancer analysis of the extent and consequences of intratumor heterogeneity

The Drug-Gene Interaction database (DGIdb) mines existing resources that generate hypotheses about how mutated genes might be targeted therapeutically or prioritized for drug development. It provides an interface for searching lists of genes against a compendium of drug-gene interactions and potentially 'druggable' genes. DGIdb can be accessed at http://dgidb.org/.

/pdf/dgidb-mining-the-druggable-genome-lnfstkjgsn.pdf

DGIdb: mining the druggable genome

In this work, we present the Genome Modeling System (GMS), an analysis information management system capable of executing automated genome analysis pipelines at a massive scale. The GMS framework provides detailed tracking of samples and data coupled with reliable and repeatable analysis pipelines. The GMS also serves as a platform for bioinformatics development, allowing a large team to collaborate on data analysis, or an individual researcher to leverage the work of others effectively within its data management system. Rather than separating ad-hoc analysis from rigorous, reproducible pipelines, the GMS promotes systematic integration between the two. As a demonstration of the GMS, we performed an integrated analysis of whole genome, exome and transcriptome sequencing data from a breast cancer cell line (HCC1395) and matched lymphoblastoid line (HCC1395BL). These data are available for users to test the software, complete tutorials and develop novel GMS pipeline configurations. The GMS is available at https://github.com/genome/gms.

/pdf/genome-modeling-system-a-knowledge-management-platform-for-4xe1qm1x8w.pdf

James V. Weible

Papers

DGIdb: mining the druggable genome

Genome Modeling System: A Knowledge Management Platform for Genomics.