British Journal of Cancer, Год журнала: 2023, Номер 128(6), С. 1095 - 1104
Опубликована: Янв. 2, 2023
Язык: Английский
Nature Communications, Год журнала: 2020, Номер 11(1)
Опубликована: Окт. 16, 2020
Abstract The Human Proteome Organization (HUPO) launched the Project (HPP) in 2010, creating an international framework for global collaboration, data sharing, quality assurance and enhancing accurate annotation of genome-encoded proteome. During subsequent decade, HPP established collaborations, developed guidelines metrics, undertook reanalysis previously deposited community data, continuously increasing coverage human On occasion HPP’s tenth anniversary, we here report a 90.4% complete high-stringency proteome blueprint. This knowledge is essential discerning molecular processes health disease, as demonstrate by highlighting potential roles plays our understanding, diagnosis treatment cancers, cardiovascular infectious diseases.
Язык: Английский
Процитировано
195
Nature reviews. Cancer, Год журнала: 2022, Номер 22(5), С. 298 - 313
Опубликована: Март 2, 2022
Язык: Английский
Процитировано
148
Cell, Год журнала: 2021, Номер 184(7), С. 1661 - 1670
Опубликована: Апрель 1, 2021
When it comes to precision oncology, proteogenomics may provide better prospects the clinical characterization of tumors, help make a more accurate diagnosis cancer, and improve treatment for patients with cancer. This perspective describes significant contributions The Cancer Genome Atlas Clinical Proteomic Tumor Analysis Consortium oncology makes case that needs be fully integrated into trials patient care in order deliver right cancer at dose time.
Язык: Английский
Процитировано
146
Nature, Год журнала: 2022, Номер 603(7902), С. 721 - 727
Опубликована: Март 9, 2022
Activated T cells secrete interferon-γ, which triggers intracellular tryptophan shortage by upregulating the indoleamine 2,3-dioxygenase 1 (IDO1) enzyme1-4. Here we show that despite depletion, in-frame protein synthesis continues across codons. We identified tryptophan-to-phenylalanine codon reassignment (W>F) as major event facilitating this process, and pinpointed tryptophanyl-tRNA synthetase (WARS1) its source. call these W>F peptides 'substitutants' to distinguish them from genetically encoded mutants. Using large-scale proteomics analyses, demonstrate substitutants be highly abundant in multiple cancer types. were enriched tumours relative matching adjacent normal tissues, associated with increased IDO1 expression, oncogenic signalling tumour-immune microenvironment. Functionally, can impair activity, but also expand landscape of antigens presented at cell surface activate responses. Thus, are generated an alternative decoding mechanism potential effects on gene function tumour immunoreactivity.
Язык: Английский
Процитировано
85
Cancer Cell, Год журнала: 2023, Номер 41(8), С. 1397 - 1406
Опубликована: Авг. 1, 2023
The National Cancer Institute's Clinical Proteomic Tumor Analysis Consortium (CPTAC) investigates tumors from a proteogenomic perspective, creating rich multi-omics datasets connecting genomic aberrations to cancer phenotypes. To facilitate pan-cancer investigations, we have generated harmonized genomic, transcriptomic, proteomic, and clinical data for >1000 in 10 cohorts create cohesive powerful dataset scientific discovery. We outline efforts by the CPTAC working group harmonization, dissemination, computational resources aiding biological discoveries. also discuss challenges integration analysis, specifically unique of with both nucleotide sequencing mass spectrometry proteomics data.
Язык: Английский
Процитировано
85
Cell, Год журнала: 2023, Номер 186(18), С. 3945 - 3967.e26
Опубликована: Авг. 1, 2023
Post-translational modifications (PTMs) play key roles in regulating cell signaling and physiology both normal cancer cells. Advances mass spectrometry enable high-throughput, accurate, sensitive measurement of PTM levels to better understand their role, prevalence, crosstalk. Here, we analyze the largest collection proteogenomics data from 1,110 patients with profiles across 11 types (10 National Cancer Institute's Clinical Proteomic Tumor Analysis Consortium [CPTAC]). Our study reveals pan-cancer patterns changes protein acetylation phosphorylation involved hallmark processes. These revealed subsets tumors, different types, including those dysregulated DNA repair driven by phosphorylation, altered metabolic regulation associated immune response acetylation, affected kinase specificity crosstalk between modified histone regulation. Overall, this resource highlights rich biology governed PTMs exposes potential new therapeutic avenues.
Язык: Английский
Процитировано
70
Cell, Год журнала: 2023, Номер 186(18), С. 3921 - 3944.e25
Опубликована: Авг. 1, 2023
Cancer driver events refer to key genetic aberrations that drive oncogenesis; however, their exact molecular mechanisms remain insufficiently understood. Here, our multi-omics pan-cancer analysis uncovers insights into the impacts of cancer drivers by identifying significant cis-effects and distal trans-effects quantified at RNA, protein, phosphoprotein levels. Salient observations include association point mutations copy-number alterations with rewiring protein interaction networks, notably, most genes converge toward similar states denoted sequence-based kinase activity profiles. A correlation between predicted neoantigen burden measured T cell infiltration suggests potential vulnerabilities for immunotherapies. Patterns hallmarks vary polygenic abundance ranging from uniform heterogeneous. Overall, work demonstrates value comprehensive proteogenomics in understanding functional oncogenic links development, surpassing limitations studying individual types.
Язык: Английский
Процитировано
54
Cell Reports, Год журнала: 2020, Номер 33(3), С. 108276 - 108276
Опубликована: Окт. 1, 2020
Many gene products exhibit great structural heterogeneity because of an array modifications. These modifications are not directly encoded in the genomic template but often affect functionality proteins. Protein glycosylation plays a vital role proper protein functions. However, analysis glycoproteins has been challenging compared with other modifications, such as phosphorylation. Here, we perform integrated proteomic and glycoproteomic 83 prospectively collected high-grade serous ovarian carcinoma (HGSC) 23 non-tumor tissues. Integration expression data from global proteomics glycoproteomics reveals tumor-specific glycosylation, uncovers different associated three tumor clusters, identifies enzymes that were correlated altered glycosylation. In addition to providing valuable resource, these results provide insights into potential roles pathogenesis HGSC, possibility distinguishing pathological outcomes tumors non-tumors, well classifying clusters.
Язык: Английский
Процитировано
117
Proceedings of the National Academy of Sciences, Год журнала: 2022, Номер 119(8)
Опубликована: Фев. 15, 2022
Retrotransposons are genomic DNA sequences that copy themselves to new locations via RNA intermediates; LINE-1 is the only active and autonomous retrotransposon in human genome. The mobility of largely repressed somatic tissues but derepressed many cancers, where retrotransposition correlated with p53 mutation number alteration (CNA). In cell lines, inducing expression can cause double-strand breaks (DSBs) replication stress. Reanalyzing multiomic data from breast, ovarian, endometrial, colon we confirmed correlations between expression, status, CNA. We observed a consistent correlation abundance complex components, indicating may also induce stress tumors. endometrial cancer, high-quality phosphoproteomic allowed us identify DSB-induced ATM-MRN-SMC S phase checkpoint pathway as primary damage response (DDR) associated expression. Induction an vitro model led increased phosphorylation MRN member RAD50, suggesting directly activates this pathway.
Язык: Английский
Процитировано
61
Cell Systems, Год журнала: 2023, Номер 14(9), С. 777 - 787.e5
Опубликована: Авг. 23, 2023
Язык: Английский
Процитировано
26