Probing the Missing Human Proteome: A Computational Perspective

Kumar, Dhirendra; Jain, Aradhya; Dash, Debasis

doi:10.1021/acs.jproteome.5b00728

Cited by 6 publications

(2 citation statements)

References 43 publications

(79 reference statements)

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“…Recent advances in instrumentation and analytical methods associated with mass spectrometry (MS)‐based proteome profiling makes it a powerful technique for probing gene expression changes at the protein level . The major goal of proteomics is to build the complete proteome map of a species which must include precise cellular localization of each protein, delineate signaling pathways and describe their regulatory PTMs . Combined with liquid chromatography (LC), tandem mass spectrometry (MS/MS) also provides a sensitive method to capture protein quantity differences .…”

Section: Introductionmentioning

confidence: 99%

Integrating transcriptome and proteome profiling: Strategies and applications

et al. 2016

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Discovering the gene expression signature associated with a cellular state is one of the basic quests in majority of biological studies. For most of the clinical and cellular manifestations, these molecular differences may be exhibited across multiple layers of gene regulation like genomic variations, gene expression, protein translation and post-translational modifications. These system wide variations are dynamic in nature and their crosstalk is overwhelmingly complex, thus analyzing them separately may not be very informative. This necessitates the integrative analysis of such multiple layers of information to understand the interplay of the individual components of the biological system. Recent developments in high throughput RNA sequencing and mass spectrometric (MS) technologies to probe transcripts and proteins made these as preferred methods for understanding global gene regulation. Subsequently, improvements in "big-data" analysis techniques enable novel conclusions to be drawn from integrative transcriptomic-proteomic analysis. The unified analyses of both these data types have been rewarding for several biological objectives like improving genome annotation, predicting RNA-protein quantities, deciphering gene regulations, discovering disease markers and drug targets. There are different ways in which transcriptomics and proteomics data can be integrated; each aiming for different research objectives. Here, we review various studies, approaches and computational tools targeted for integrative analysis of these two high-throughput omics methods.

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Section: Introductionmentioning

confidence: 99%

Integrating transcriptome and proteome profiling: Strategies and applications

et al. 2016

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“…In EuGenoSuite, only OMSSA and X!Tandem are configured to search MS data against extra-large eukaryotic databases in a timely fashion. It has also been successfully used in our recent work to identify missing human proteins (37).…”

Section: Methodsmentioning

confidence: 99%

Integrated Transcriptomic-Proteomic Analysis Using a Proteogenomic Workflow Refines Rat Genome Annotation

Kumar

Yadav

Jia

et al. 2016

Molecular & Cellular Proteomics

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Proteogenomic re-annotation and mRNA splicing information can lead to the discovery of various protein forms for eukaryotic model organisms like rat. However, detection of novel proteoforms using mass spectrometry proteomics data remains a formidable challenge. We developed EuGenoSuite, an open source multiple algorithmic proteomic search tool and utilized it in our in-house integrated transcriptomic-proteomic pipeline to facilitate automated proteogenomic analysis. Using four proteogenomic pipelines (integrated transcriptomic-proteomic, Peppy, Enosi, and ProteoAnnotator) on publicly available RNA-sequence and MS proteomics data, we discovered 363 novel peptides in rat brain microglia representing novel proteoforms for 249 gene loci in the rat genome. These novel peptides aided in the discovery of novel exons, translation of annotated untranslated regions, pseudogenes, and splice variants for various loci; many of which have known disease associations, including neurological disorders like schizophrenia, amyotrophic lateral sclerosis, etc. Novel isoforms were also discovered for genes implicated in cardiovascular diseases and breast cancer for which rats are considered model organisms. Our integrative multi-omics data analysis not only enables the discovery of new proteoforms but also generates an improved reference for human disease studies in the rat model. Molecular & Cellular

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Proteogenomic Tools and Approaches to Explore Protein Coding Landscapes of Eukaryotic Genomes

Kumar

Dash

2016

Advances in Experimental Medicine and Biology

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Proteogenomic strategies aim to refine genome-wide annotations of protein coding features by using actual protein level observations. Most of the currently applied proteogenomic approaches include integrative analysis of multiple types of high-throughput omics data, e.g., genomics, transcriptomics, proteomics, etc. Recent efforts towards creating a human proteome map were primarily targeted to experimentally detect at least one protein product for each gene in the genome and extensively utilized proteogenomic approaches. The 14 year long wait to get a draft human proteome map, after completion of similar efforts to sequence the genome, explains the huge complexity and technical hurdles of such efforts. Further, the integrative analysis of large-scale multi-omics datasets inherent to these studies becomes a major bottleneck to their success. However, recent developments of various analysis tools and pipelines dedicated to proteogenomics reduce both the time and complexity of such analysis. Here, we summarize notable approaches, studies, software developments and their potential applications towards eukaryotic genome annotation and clinical proteogenomics.

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Probing the Missing Human Proteome: A Computational Perspective

Cited by 6 publications

References 43 publications

Integrating transcriptome and proteome profiling: Strategies and applications

Integrating transcriptome and proteome profiling: Strategies and applications

Integrated Transcriptomic-Proteomic Analysis Using a Proteogenomic Workflow Refines Rat Genome Annotation

Proteogenomic Tools and Approaches to Explore Protein Coding Landscapes of Eukaryotic Genomes

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