Proteogenomic Analysis of Breast Cancer Transcriptomic and Proteomic Data, Using De Novo Transcript Assembly: Genome-Wide Identification of Novel Peptides and Clinical Implications

Hari, Parameswaran; Balakrishnan, Lavanya; Kotyada, Chaithanya; John, Arivusudar Everad; Tiwary, Shivani; Shah, Nameeta; Sirdeshmukh, Ravi

doi:10.1016/j.mcpro.2022.100220

Cited by 10 publications

(10 citation statements)

References 55 publications

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“…Such a large amount of data facilitates their re-use for applications beyond the originally intended ones (Perez-Riverol et al 2015; Martens and Vizcaíno 2017). Proteogenomics, which combines multi-omic data sets, may be one of the growing focuses of these proteomic data re-use activities (Hari et al 2022; Robin et al 2018).…”

Section: Introductionmentioning

confidence: 99%

Massive proteogenomic reanalysis of publicly available proteomic datasets of human tissues in search for protein recoding via adenosine-to-inosine RNA editing

Levitsky

Ivanov

Goncharov³

et al. 2022

Preprint

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The proteogenomic search pipeline developed in this work has been applied for re-analysis of 40 publicly available shotgun proteomic datasets from various human tissues comprising more than 8,000 individual LC-MS/MS runs, of which 5442 .raw data files were processed in total. The scope of this re-analysis was focused on searching for ADAR-mediated RNA editing events, their clustering across samples of different origin, and classification. In total, 33 recoded protein sites were identified in 21 datasets. Of those, 18 sites were detected in at least two datasets representing the core human protein editome. In agreement with prior art works, neural and cancer tissues were found being enriched with recoded proteins. Quantitative analysis indicated that recoding of specific sites did not directly depend on the levels of ADAR enzymes or targeted proteins themselves, rather it was provided by differential and yet undescribed regulation of interaction of enzymes with mRNA. Nine recoding sites conservative between human and rodents were validated by targeted proteomics using stable isotope standards in murine brain cortex and cerebellum, and an additional one was validated in human cerebrospinal fluid. In addition to previous data of the same type from cancer proteomes, we provide a comprehensive catalog of recoding events caused by ADAR RNA editing in the human proteome.

show abstract

Section: Introductionmentioning

confidence: 99%

Massive proteogenomic reanalysis of publicly available proteomic datasets of human tissues in search for protein recoding via adenosine-to-inosine RNA editing

Levitsky

Ivanov

Goncharov³

et al. 2022

Preprint

View full text Add to dashboard Cite

show abstract

“…18,19 Proteogenomics, which combines multi-omic data sets, may be one of the growing focuses of these proteomic data reuse activities. 20,21 Adenosine-to-inosine RNA editing is one of the interesting areas of proteogenomic research and may involve data reanalysis to search for the associated protein sequence variants. This evolutionary ancient posttranscriptional modification of RNA is catalyzed by adenosine deaminases of the ADAR family.…”

Section: ■ Introductionmentioning

confidence: 99%

“…Currently, it has well over 14,000 proteomic project datasets with half of them related to human samples . Such a large amount of data facilitates their reuse for applications beyond the originally intended ones. , Proteogenomics, which combines multi-omic data sets, may be one of the growing focuses of these proteomic data reuse activities. , …”

Section: Introductionmentioning

confidence: 99%

Massive Proteogenomic Reanalysis of Publicly Available Proteomic Datasets of Human Tissues in Search for Protein Recoding via Adenosine-to-Inosine RNA Editing

et al. 2023

View full text Add to dashboard Cite

The proteogenomic search pipeline developed in this work has been applied for reanalysis of 40 publicly available shotgun proteomic datasets from various human tissues comprising more than 8000 individual LC–MS/MS runs, of which 5442 .raw data files were processed in total. This reanalysis was focused on searching for ADAR-mediated RNA editing events, their clustering across samples of different origins, and classification. In total, 33 recoded protein sites were identified in 21 datasets. Of those, 18 sites were detected in at least two datasets, representing the core human protein editome. In agreement with prior artworks, neural and cancer tissues were found to be enriched with recoded proteins. Quantitative analysis indicated that recoding the rate of specific sites did not directly depend on the levels of ADAR enzymes or targeted proteins themselves, rather it was governed by differential and yet undescribed regulation of interaction of enzymes with mRNA. Nine recoding sites conservative between humans and rodents were validated by targeted proteomics using stable isotope standards in the murine brain cortex and cerebellum, and an additional one was validated in human cerebrospinal fluid. In addition to previous data of the same type from cancer proteomes, we provide a comprehensive catalog of recoding events caused by ADAR RNA editing in the human proteome.

show abstract

“…For instance, 4387 novel peptides were identified through proteogenomic analysis of breast cancer data. Most of these novel peptides were derived from novel proteins that are not included in widely used gene catalogs ( 25 ). In another study, with proteomic data from 95 projects, the OpenProt project identified 48,057 novel peptides based on known genic regions in the RefSeq and Ensembl gene catalogs ( 26 ).…”

mentioning

confidence: 99%

“…, SmProt, sORF) ( 27 , 28 ), and many focus on proteomes of a single disease/phenotype ( e.g. , breast cancer study) ( 25 ). Because many ncORFs were not included in the RefSeq and Ensembl transcripts and many proteomic studies did not include sample-specific transcriptome to predict ncORFs for proteogenomic search, a comprehensive proteogenomic survey of novel proteins in diverse range of tissues, sample types, and disease conditions is still lacking.…”

mentioning

confidence: 99%

A Massive Proteogenomic Screen Identifies Thousands of Novel Peptides From the Human “Dark” Proteome

Cao,

Sun,

Xing

2024

Molecular & Cellular Proteomics

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Proteogenomic Analysis of Breast Cancer Transcriptomic and Proteomic Data, Using De Novo Transcript Assembly: Genome-Wide Identification of Novel Peptides and Clinical Implications

Cited by 10 publications

References 55 publications

Massive proteogenomic reanalysis of publicly available proteomic datasets of human tissues in search for protein recoding via adenosine-to-inosine RNA editing

Massive proteogenomic reanalysis of publicly available proteomic datasets of human tissues in search for protein recoding via adenosine-to-inosine RNA editing

Massive Proteogenomic Reanalysis of Publicly Available Proteomic Datasets of Human Tissues in Search for Protein Recoding via Adenosine-to-Inosine RNA Editing

A Massive Proteogenomic Screen Identifies Thousands of Novel Peptides From the Human “Dark” Proteome

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