Footprint-based functional analysis of multiomic data

Omic technologies allow us to generate extensive data, including transcriptomic, proteomic, phosphoproteomic and metabolomic. These data can be used to study signal transduction, gene regulation and metabolism. In this review, we summarise resources and methods to analysis these types of data. We focus on methods developed to recover functional insights using footprints. Footprints are signatures defined by the effect of molecules or processes of interest. They integrate information from multiple measurements whose abundances are under the influence of a common regulator. For example, transcripts controlled by a transcription factor or peptides phosphorylated by a kinase. Footprints can also be generalised across multiple types of omic data. Thus, we also present methods to integrate multiple types of omic data and features (such as the ones derived from footprints) together. We highlight some examples of studies that leverage such approaches to discover new biological mechanisms.

[1]  Mehmet Koyutürk,et al.  The KSEA App: a web‐based tool for kinase activity inference from quantitative phosphoproteomics , 2017, Bioinform..

[2]  Bertram Klinger,et al.  Discovering causal signaling pathways through gene-expression patterns , 2010, Nucleic Acids Res..

[3]  Panuwat Trairatphisan,et al.  From expression footprints to causal pathways: contextualizing large signaling networks with CARNIVAL , 2019, npj Systems Biology and Applications.

[4]  J. Sáez-Rodríguez,et al.  Perturbation-response genes reveal signaling footprints in cancer gene expression , 2016, Nature Communications.

[5]  Expression and activity of multidrug resistance proteins in mature endothelial cells and their precursors: A challenging correlation , 2017, PloS one.

[6]  Nils Blüthgen,et al.  Classification of gene signatures for their information value and functional redundancy , 2017, npj Systems Biology and Applications.

[7]  A. McKenna,et al.  Synthesizing Signaling Pathways from Temporal Phosphoproteomic Data , 2017, bioRxiv.

[8]  Helga Thorvaldsdóttir,et al.  Molecular signatures database (MSigDB) 3.0 , 2011, Bioinform..

[9]  Hyojin Kim,et al.  TRRUST v2: an expanded reference database of human and mouse transcriptional regulatory interactions , 2017, Nucleic Acids Res..

[10]  Glyn Bradley,et al.  CausalR: extracting mechanistic sense from genome scale data , 2017, Bioinform..

[11]  Antje Chang,et al.  BRENDA in 2019: a European ELIXIR core data resource , 2018, Nucleic Acids Res..

[12]  Susumu Goto,et al.  KEGG: Kyoto Encyclopedia of Genes and Genomes , 2000, Nucleic Acids Res..

[13]  Henning Hermjakob,et al.  The Reactome pathway Knowledgebase , 2015, Nucleic acids research.

[14]  Seon-Young Kim,et al.  PAGE: Parametric Analysis of Gene Set Enrichment , 2005, BMC Bioinform..

[15]  Gary D. Bader,et al.  Pathway Commons, a web resource for biological pathway data , 2010, Nucleic Acids Res..

[16]  Evan O. Paull,et al.  Phosphoproteome Integration Reveals Patient-Specific Networks in Prostate Cancer , 2016, Cell.

[17]  Korbinian Strimmer,et al.  A general modular framework for gene set enrichment analysis , 2009, BMC Bioinformatics.

[18]  Ernest Fraenkel,et al.  Revealing disease-associated pathways by network integration of untargeted metabolomics , 2016, Nature Methods.

[19]  Jihye Kim,et al.  DSigDB: drug signatures database for gene set analysis , 2015, Bioinform..

[20]  E. Ruppin,et al.  A joint analysis of transcriptomic and metabolomic data uncovers enhanced enzyme-metabolite coupling in breast cancer , 2016, Scientific Reports.

[21]  Ali Ebrahim,et al.  Multi-omic data integration enables discovery of hidden biological regularities , 2016, Nature Communications.

[22]  Fang-Xiang Wu,et al.  Identifying protein complexes and functional modules - from static PPI networks to dynamic PPI networks , 2014, Briefings Bioinform..

[23]  Sudha Ramaiah,et al.  Discerning molecular interactions: A comprehensive review on biomolecular interaction databases and network analysis tools. , 2018, Gene.

[24]  Christina S. Leslie,et al.  Pancancer modelling predicts the context-specific impact of somatic mutations on transcriptional programs , 2017, Nature Communications.

[25]  Damian Szklarczyk,et al.  STITCH 5: augmenting protein–chemical interaction networks with tissue and affinity data , 2015, Nucleic Acids Res..

[26]  Bin Zhang,et al.  PhosphoSitePlus: a comprehensive resource for investigating the structure and function of experimentally determined post-translational modifications in man and mouse , 2011, Nucleic Acids Res..

[27]  Andrew D. Rouillard,et al.  Enrichr: a comprehensive gene set enrichment analysis web server 2016 update , 2016, Nucleic Acids Res..

[28]  David Gomez-Cabrero,et al.  ChainRank, a chain prioritisation method for contextualisation of biological networks , 2016, BMC Bioinformatics.

[29]  Shila Ghazanfar,et al.  KinasePA: Phosphoproteomics data annotation using hypothesis driven kinase perturbation analysis , 2016, Proteomics.

[30]  Yutaka Suzuki,et al.  Trans-omic Analysis Reveals Selective Responses to Induced and Basal Insulin across Signaling, Transcriptional, and Metabolic Networks , 2018, iScience.

[31]  Benjamin J. Raphael,et al.  Hierarchical HotNet: identifying hierarchies of altered subnetworks , 2018, Bioinform..

[32]  Pedro Beltrão,et al.  Systematic Analysis of Transcriptional and Post-transcriptional Regulation of Metabolism in Yeast , 2016, bioRxiv.

[33]  Emanuel J. V. Gonçalves,et al.  Post-translational regulation of metabolism in fumarate hydratase deficient cancer cells , 2017, bioRxiv.

[34]  Brad T. Sherman,et al.  Systematic and integrative analysis of large gene lists using DAVID bioinformatics resources , 2008, Nature Protocols.

[35]  M. Ashburner,et al.  Gene Ontology: tool for the unification of biology , 2000, Nature Genetics.

[36]  Z. Nikoloski,et al.  Data Reduction Approaches for Dissecting Transcriptional Effects on Metabolism , 2018, Front. Plant Sci..

[37]  Mariano J. Alvarez,et al.  Network-based inference of protein activity helps functionalize the genetic landscape of cancer , 2016, Nature Genetics.

[38]  Julio Saez-Rodriguez,et al.  OmniPath: guidelines and gateway for literature-curated signaling pathway resources , 2016, Nature Methods.

[39]  Jill P. Mesirov,et al.  A Curated Resource for Phosphosite-specific Signature Analysis* , 2018, Molecular & Cellular Proteomics.

[40]  Angela N. Brooks,et al.  A Next Generation Connectivity Map: L1000 Platform and the First 1,000,000 Profiles , 2017, Cell.

[41]  Mehmet Koyutürk,et al.  CoPhosK: A Method for Comprehensive Kinase Substrate Annotation Using Co-phosphorylation Analysis , 2018 .

[42]  Monther Alhamdoosh,et al.  Combining multiple tools outperforms individual methods in gene set enrichment analyses , 2015, bioRxiv.

[43]  Alexander E. Kel,et al.  TRANSFAC® and its module TRANSCompel®: transcriptional gene regulation in eukaryotes , 2005, Nucleic Acids Res..

[44]  Autonomous Multimodal Metabolomics Data Integration for Comprehensive Pathway Analysis and Systems Biology. , 2018, Analytical chemistry.

[45]  Avlant Nilsson,et al.  Recon3D: A Resource Enabling A Three-Dimensional View of Gene Variation in Human Metabolism , 2018, Nature Biotechnology.

[46]  Sun Kim,et al.  Comprehensive and critical evaluation of individualized pathway activity measurement tools on pan-cancer data , 2018, Briefings Bioinform..

[47]  Avi Ma'ayan,et al.  KEA: kinase enrichment analysis , 2009, Bioinform..

[48]  L. Jensen,et al.  KinomeXplorer: an integrated platform for kinome biology studies , 2014, Nature Methods.

[49]  J. Saez-Rodriguez,et al.  Large-scale models of signal propagation in human cells derived from discovery phosphoproteomic data , 2015, Nature Communications.

[50]  J. Marioni,et al.  Multi‐Omics Factor Analysis—a framework for unsupervised integration of multi‐omics data sets , 2018, Molecular systems biology.

[51]  Nuno A. Fonseca,et al.  Transcription Factor Activities Enhance Markers of Drug Sensitivity in Cancer. , 2018, Cancer research.

[52]  J. Sáez-Rodríguez,et al.  Benchmark and integration of resources for the estimation of human transcription factor activities , 2018, bioRxiv.

[53]  Pedro Beltrão,et al.  Benchmarking substrate-based kinase activity inference using phosphoproteomic data , 2016, bioRxiv.

[54]  Pablo Tamayo,et al.  Gene set enrichment analysis: A knowledge-based approach for interpreting genome-wide expression profiles , 2005, Proceedings of the National Academy of Sciences of the United States of America.

[55]  S. Joel,et al.  Kinase-Substrate Enrichment Analysis Provides Insights into the Heterogeneity of Signaling Pathway Activation in Leukemia Cells , 2013, Science Signaling.

[56]  Joaquín Dopazo,et al.  A comparison of mechanistic signaling pathway activity analysis methods , 2018, Briefings Bioinform..

[57]  Davide Heller,et al.  STRING v10: protein–protein interaction networks, integrated over the tree of life , 2014, Nucleic Acids Res..