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Your search keyword '"Omelchenko, Tatiana"' showing total 5 results
Start Over Author "Omelchenko, Tatiana" Topic proteogenomics
5 results on '"Omelchenko, Tatiana"'

1. Proteogenomic insights suggest druggable pathways in endometrial carcinoma.

Author

Dou Y, Katsnelson L, Gritsenko MA, Hu Y, Reva B, Hong R, Wang YT, Kolodziejczak I, Lu RJ, Tsai CF, Bu W, Liu W, Guo X, An E, Arend RC, Bavarva J, Chen L, Chu RK, Czekański A, Davoli T, Demicco EG, DeLair D, Devereaux K, Dhanasekaran SM, Dottino P, Dover B, Fillmore TL, Foxall M, Hermann CE, Hiltke T, Hostetter G, Jędryka M, Jewell SD, Johnson I, Kahn AG, Ku AT, Kumar-Sinha C, Kurzawa P, Lazar AJ, Lazcano R, Lei JT, Li Y, Liao Y, Lih TM, Lin TT, Martignetti JA, Masand RP, Matkowski R, McKerrow W, Mesri M, Monroe ME, Moon J, Moore RJ, Nestor MD, Newton C, Omelchenko T, Omenn GS, Payne SH, Petyuk VA, Robles AI, Rodriguez H, Ruggles KV, Rykunov D, Savage SR, Schepmoes AA, Shi T, Shi Z, Tan J, Taylor M, Thiagarajan M, Wang JM, Weitz KK, Wen B, Williams CM, Wu Y, Wyczalkowski MA, Yi X, Zhang X, Zhao R, Mutch D, Chinnaiyan AM, Smith RD, Nesvizhskii AI, Wang P, Wiznerowicz M, Ding L, Mani DR, Zhang H, Anderson ML, Rodland KD, Zhang B, Liu T, and Fenyö D

Subjects
Female, Humans, Proto-Oncogene Proteins c-akt genetics, Prospective Studies, beta Catenin genetics, beta Catenin metabolism, Proteogenomics, Endometrial Neoplasms drug therapy, Endometrial Neoplasms genetics, Endometrial Neoplasms metabolism, Metformin pharmacology
Abstract

We characterized a prospective endometrial carcinoma (EC) cohort containing 138 tumors and 20 enriched normal tissues using 10 different omics platforms. Targeted quantitation of two peptides can predict antigen processing and presentation machinery activity, and may inform patient selection for immunotherapy. Association analysis between MYC activity and metformin treatment in both patients and cell lines suggests a potential role for metformin treatment in non-diabetic patients with elevated MYC activity. PIK3R1 in-frame indels are associated with elevated AKT phosphorylation and increased sensitivity to AKT inhibitors. CTNNB1 hotspot mutations are concentrated near phosphorylation sites mediating pS45-induced degradation of β-catenin, which may render Wnt-FZD antagonists ineffective. Deep learning accurately predicts EC subtypes and mutations from histopathology images, which may be useful for rapid diagnosis. Overall, this study identified molecular and imaging markers that can be further investigated to guide patient stratification for more precise treatment of EC., Competing Interests: Declaration of interests The authors declare no competing interests., (Published by Elsevier Inc.)

Published
2023
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2. A proteogenomic portrait of lung squamous cell carcinoma.

Author

Satpathy S, Krug K, Jean Beltran PM, Savage SR, Petralia F, Kumar-Sinha C, Dou Y, Reva B, Kane MH, Avanessian SC, Vasaikar SV, Krek A, Lei JT, Jaehnig EJ, Omelchenko T, Geffen Y, Bergstrom EJ, Stathias V, Christianson KE, Heiman DI, Cieslik MP, Cao S, Song X, Ji J, Liu W, Li K, Wen B, Li Y, Gümüş ZH, Selvan ME, Soundararajan R, Visal TH, Raso MG, Parra ER, Babur Ö, Vats P, Anand S, Schraink T, Cornwell M, Rodrigues FM, Zhu H, Mo CK, Zhang Y, da Veiga Leprevost F, Huang C, Chinnaiyan AM, Wyczalkowski MA, Omenn GS, Newton CJ, Schurer S, Ruggles KV, Fenyö D, Jewell SD, Thiagarajan M, Mesri M, Rodriguez H, Mani SA, Udeshi ND, Getz G, Suh J, Li QK, Hostetter G, Paik PK, Dhanasekaran SM, Govindan R, Ding L, Robles AI, Clauser KR, Nesvizhskii AI, Wang P, Carr SA, Zhang B, Mani DR, and Gillette MA

Subjects
Acetylation, Adult, Aged, Aged, 80 and over, Cluster Analysis, Cyclin-Dependent Kinase 4 genetics, Cyclin-Dependent Kinase 6 genetics, Epithelial-Mesenchymal Transition genetics, Female, Gene Expression Regulation, Neoplastic, Humans, Male, Middle Aged, Mutation genetics, Neoplasm Proteins metabolism, Phosphorylation, Protein Binding, Receptor Tyrosine Kinase-like Orphan Receptors metabolism, Receptors, Platelet-Derived Growth Factor metabolism, Signal Transduction, Ubiquitination, Carcinoma, Squamous Cell genetics, Lung Neoplasms genetics, Proteogenomics
Abstract

Lung squamous cell carcinoma (LSCC) remains a leading cause of cancer death with few therapeutic options. We characterized the proteogenomic landscape of LSCC, providing a deeper exposition of LSCC biology with potential therapeutic implications. We identify NSD3 as an alternative driver in FGFR1-amplified tumors and low-p63 tumors overexpressing the therapeutic target survivin. SOX2 is considered undruggable, but our analyses provide rationale for exploring chromatin modifiers such as LSD1 and EZH2 to target SOX2-overexpressing tumors. Our data support complex regulation of metabolic pathways by crosstalk between post-translational modifications including ubiquitylation. Numerous immune-related proteogenomic observations suggest directions for further investigation. Proteogenomic dissection of CDKN2A mutations argue for more nuanced assessment of RB1 protein expression and phosphorylation before declaring CDK4/6 inhibition unsuccessful. Finally, triangulation between LSCC, LUAD, and HNSCC identified both unique and common therapeutic vulnerabilities. These observations and proteogenomics data resources may guide research into the biology and treatment of LSCC., Competing Interests: Declaration of interests The authors declare no competing interests., (Copyright © 2021 The Author(s). Published by Elsevier Inc. All rights reserved.)

Published
2021
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3. Integrated Proteogenomic Characterization across Major Histological Types of Pediatric Brain Cancer.

Author

Petralia F, Tignor N, Reva B, Koptyra M, Chowdhury S, Rykunov D, Krek A, Ma W, Zhu Y, Ji J, Calinawan A, Whiteaker JR, Colaprico A, Stathias V, Omelchenko T, Song X, Raman P, Guo Y, Brown MA, Ivey RG, Szpyt J, Guha Thakurta S, Gritsenko MA, Weitz KK, Lopez G, Kalayci S, Gümüş ZH, Yoo S, da Veiga Leprevost F, Chang HY, Krug K, Katsnelson L, Wang Y, Kennedy JJ, Voytovich UJ, Zhao L, Gaonkar KS, Ennis BM, Zhang B, Baubet V, Tauhid L, Lilly JV, Mason JL, Farrow B, Young N, Leary S, Moon J, Petyuk VA, Nazarian J, Adappa ND, Palmer JN, Lober RM, Rivero-Hinojosa S, Wang LB, Wang JM, Broberg M, Chu RK, Moore RJ, Monroe ME, Zhao R, Smith RD, Zhu J, Robles AI, Mesri M, Boja E, Hiltke T, Rodriguez H, Zhang B, Schadt EE, Mani DR, Ding L, Iavarone A, Wiznerowicz M, Schürer S, Chen XS, Heath AP, Rokita JL, Nesvizhskii AI, Fenyö D, Rodland KD, Liu T, Gygi SP, Paulovich AG, Resnick AC, Storm PB, Rood BR, and Wang P

Subjects
Brain Neoplasms immunology, Child, DNA Copy Number Variations genetics, Gene Expression Regulation, Neoplastic, Gene Regulatory Networks, Genome, Human, Glioma genetics, Glioma pathology, Humans, Lymphocytes, Tumor-Infiltrating immunology, Mutation genetics, Neoplasm Grading, Neoplasm Recurrence, Local pathology, Phosphoproteins metabolism, Phosphorylation, RNA, Messenger genetics, RNA, Messenger metabolism, Transcriptome genetics, Brain Neoplasms genetics, Brain Neoplasms pathology, Proteogenomics
Abstract

We report a comprehensive proteogenomics analysis, including whole-genome sequencing, RNA sequencing, and proteomics and phosphoproteomics profiling, of 218 tumors across 7 histological types of childhood brain cancer: low-grade glioma (n = 93), ependymoma (32), high-grade glioma (25), medulloblastoma (22), ganglioglioma (18), craniopharyngioma (16), and atypical teratoid rhabdoid tumor (12). Proteomics data identify common biological themes that span histological boundaries, suggesting that treatments used for one histological type may be applied effectively to other tumors sharing similar proteomics features. Immune landscape characterization reveals diverse tumor microenvironments across and within diagnoses. Proteomics data further reveal functional effects of somatic mutations and copy number variations (CNVs) not evident in transcriptomics data. Kinase-substrate association and co-expression network analysis identify important biological mechanisms of tumorigenesis. This is the first large-scale proteogenomics analysis across traditional histological boundaries to uncover foundational pediatric brain tumor biology and inform rational treatment selection., Competing Interests: Declaration of Interests E.E.S. serves as chief executive officer for Sema4 and has an equity interest in this company., (Copyright © 2020 Elsevier Inc. All rights reserved.)

Published
2020
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4. Proteogenomic Characterization Reveals Therapeutic Vulnerabilities in Lung Adenocarcinoma.

Author

Gillette MA, Satpathy S, Cao S, Dhanasekaran SM, Vasaikar SV, Krug K, Petralia F, Li Y, Liang WW, Reva B, Krek A, Ji J, Song X, Liu W, Hong R, Yao L, Blumenberg L, Savage SR, Wendl MC, Wen B, Li K, Tang LC, MacMullan MA, Avanessian SC, Kane MH, Newton CJ, Cornwell M, Kothadia RB, Ma W, Yoo S, Mannan R, Vats P, Kumar-Sinha C, Kawaler EA, Omelchenko T, Colaprico A, Geffen Y, Maruvka YE, da Veiga Leprevost F, Wiznerowicz M, Gümüş ZH, Veluswamy RR, Hostetter G, Heiman DI, Wyczalkowski MA, Hiltke T, Mesri M, Kinsinger CR, Boja ES, Omenn GS, Chinnaiyan AM, Rodriguez H, Li QK, Jewell SD, Thiagarajan M, Getz G, Zhang B, Fenyö D, Ruggles KV, Cieslik MP, Robles AI, Clauser KR, Govindan R, Wang P, Nesvizhskii AI, Ding L, Mani DR, and Carr SA

Subjects
Adenocarcinoma of Lung immunology, Adult, Aged, Aged, 80 and over, Biomarkers, Tumor metabolism, Carcinogenesis genetics, Carcinogenesis pathology, DNA Copy Number Variations genetics, DNA Methylation genetics, Female, Humans, Lung Neoplasms immunology, Male, Middle Aged, Mutation genetics, Oncogene Proteins, Fusion, Phenotype, Phosphoproteins metabolism, Proteome metabolism, Adenocarcinoma of Lung drug therapy, Adenocarcinoma of Lung genetics, Lung Neoplasms drug therapy, Lung Neoplasms genetics, Proteogenomics
Abstract

To explore the biology of lung adenocarcinoma (LUAD) and identify new therapeutic opportunities, we performed comprehensive proteogenomic characterization of 110 tumors and 101 matched normal adjacent tissues (NATs) incorporating genomics, epigenomics, deep-scale proteomics, phosphoproteomics, and acetylproteomics. Multi-omics clustering revealed four subgroups defined by key driver mutations, country, and gender. Proteomic and phosphoproteomic data illuminated biology downstream of copy number aberrations, somatic mutations, and fusions and identified therapeutic vulnerabilities associated with driver events involving KRAS, EGFR, and ALK. Immune subtyping revealed a complex landscape, reinforced the association of STK11 with immune-cold behavior, and underscored a potential immunosuppressive role of neutrophil degranulation. Smoking-associated LUADs showed correlation with other environmental exposure signatures and a field effect in NATs. Matched NATs allowed identification of differentially expressed proteins with potential diagnostic and therapeutic utility. This proteogenomics dataset represents a unique public resource for researchers and clinicians seeking to better understand and treat lung adenocarcinomas., Competing Interests: Declaration of Interests B.Z. has received research funding from Bristol-Myers Squibb. All other authors have no conflict of interests to declare., (Copyright © 2020 Elsevier Inc. All rights reserved.)

Published
2020
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5. Integrated Proteogenomic Characterization of Clear Cell Renal Cell Carcinoma.

Author

Clark DJ, Dhanasekaran SM, Petralia F, Pan J, Song X, Hu Y, da Veiga Leprevost F, Reva B, Lih TM, Chang HY, Ma W, Huang C, Ricketts CJ, Chen L, Krek A, Li Y, Rykunov D, Li QK, Chen LS, Ozbek U, Vasaikar S, Wu Y, Yoo S, Chowdhury S, Wyczalkowski MA, Ji J, Schnaubelt M, Kong A, Sethuraman S, Avtonomov DM, Ao M, Colaprico A, Cao S, Cho KC, Kalayci S, Ma S, Liu W, Ruggles K, Calinawan A, Gümüş ZH, Geiszler D, Kawaler E, Teo GC, Wen B, Zhang Y, Keegan S, Li K, Chen F, Edwards N, Pierorazio PM, Chen XS, Pavlovich CP, Hakimi AA, Brominski G, Hsieh JJ, Antczak A, Omelchenko T, Lubinski J, Wiznerowicz M, Linehan WM, Kinsinger CR, Thiagarajan M, Boja ES, Mesri M, Hiltke T, Robles AI, Rodriguez H, Qian J, Fenyö D, Zhang B, Ding L, Schadt E, Chinnaiyan AM, Zhang Z, Omenn GS, Cieslik M, Chan DW, Nesvizhskii AI, Wang P, and Zhang H

Subjects
Adult, Aged, Aged, 80 and over, Biomarkers, Tumor genetics, Biomarkers, Tumor immunology, Carcinoma, Renal Cell immunology, Carcinoma, Renal Cell pathology, Disease-Free Survival, Exome genetics, Female, Gene Expression Regulation, Neoplastic genetics, Genome, Human genetics, Humans, Male, Middle Aged, Neoplasm Proteins immunology, Oxidative Phosphorylation, Phosphorylation genetics, Signal Transduction genetics, Transcriptome immunology, Tumor Microenvironment genetics, Tumor Microenvironment immunology, Exome Sequencing, Carcinoma, Renal Cell genetics, Neoplasm Proteins genetics, Proteogenomics, Transcriptome genetics
Abstract

To elucidate the deregulated functional modules that drive clear cell renal cell carcinoma (ccRCC), we performed comprehensive genomic, epigenomic, transcriptomic, proteomic, and phosphoproteomic characterization of treatment-naive ccRCC and paired normal adjacent tissue samples. Genomic analyses identified a distinct molecular subgroup associated with genomic instability. Integration of proteogenomic measurements uniquely identified protein dysregulation of cellular mechanisms impacted by genomic alterations, including oxidative phosphorylation-related metabolism, protein translation processes, and phospho-signaling modules. To assess the degree of immune infiltration in individual tumors, we identified microenvironment cell signatures that delineated four immune-based ccRCC subtypes characterized by distinct cellular pathways. This study reports a large-scale proteogenomic analysis of ccRCC to discern the functional impact of genomic alterations and provides evidence for rational treatment selection stemming from ccRCC pathobiology., (Copyright © 2019 Elsevier Inc. All rights reserved.)

Published
2019
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