Multi-Omics Profiling for Health

Molecular & Cellular Proteomics, Год журнала: 2023, Номер 22(6), С. 100561 - 100561

Опубликована: Апрель 28, 2023

The world has witnessed a steady rise in both non-infectious and infectious chronic diseases, prompting cross-disciplinary approach to understand treating disease. Current medical care focuses on people after they become patients rather than preventing illness, leading high costs late-stage diseases. Additionally, "one-size-fits all" health does not take into account individual differences genetics, environment, or lifestyle factors, decreasing the number of benefiting from interventions. Rapid advances omics technologies progress computational capabilities have led development multi-omics deep phenotyping, which profiles interaction multiple levels biology over time empowers precision approaches. This review highlights current emerging modalities for discusses applications following areas: genetic variation, cardio-metabolic cancer, organ transplantation, pregnancy, longevity/aging. We will briefly discuss potential approaches disentangling host-microbe host-environmental interactions. touch areas electronic record clinical imaging integration with muti-omics health. Finally, we challenges implementation its future prospects.

Язык: Английский

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Proteogenomic data and resources for pan-cancer analysis

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

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Pharmacogenomics: Driving Personalized Medicine

Pharmacological Reviews, Год журнала: 2023, Номер 75(4), С. 789 - 814

Опубликована: Март 16, 2023

Abstract

Personalized medicine tailors therapies, disease prevention, and health maintenance to the individual, with pharmacogenomics serving as a key tool improve outcomes prevent adverse effects. Advances in genomics have transformed pharmacogenetics, traditionally focused on single gene-drug pairs, into pharmacogenomics, encompassing all "-omics" fields (e.g., proteomics, transcriptomics, metabolomics, metagenomics). This review summarizes basic principles relevant translation assessing pharmacogenomics' central role converging diverse elements of personalized medicine. We discuss genetic variations pharmacogenes (drug-metabolizing enzymes, drug transporters, receptors), their clinical relevance biomarkers, legacy decades research pharmacogenetics. All types including proteins, nucleic acids, viruses, cells, genes, irradiation, can benefit from genomics, expanding across Food Drug Administration approvals therapeutics involving biomarkers increase rapidly, demonstrating growing impact pharmacogenomics. A beacon for therapeutic approaches, molecularly targeted cancer therapies highlight trends discovery applications. To account human complexity, multicomponent biomarker panels genetic, personal, environmental factors guide diagnosis increasingly artificial intelligence cope extreme data complexities. However, application encounters substantial hurdles, such unknown validity ethnic groups, underlying bias care, real-world validation. address science technologies germane medicine, integrated economic, ethical, regulatory issues, providing insights current status future direction care.

Significance Statement

aims optimize care individual patients use predictive Pharmacogenomics drives guides development therapeutics. addresses large-scale repositories accelerating medical advances. The is discussed, along hurdles impeding broad implementation, context ethics, economics, affairs.

Язык: Английский

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Pan-cancer analysis of post-translational modifications reveals shared patterns of protein regulation

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

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Advancing CAR T cell therapy through the use of multidimensional omics data

Nature Reviews Clinical Oncology, Год журнала: 2023, Номер 20(4), С. 211 - 228

Опубликована: Янв. 31, 2023

Язык: Английский

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Pan-cancer proteogenomics expands the landscape of therapeutic targets

Cell, Год журнала: 2024, Номер 187(16), С. 4389 - 4407.e15

Опубликована: Июнь 24, 2024

Fewer than 200 proteins are targeted by cancer drugs approved the Food and Drug Administration (FDA). We integrate Clinical Proteomic Tumor Analysis Consortium (CPTAC) proteogenomics data from 1,043 patients across 10 types with additional public datasets to identify potential therapeutic targets. Pan-cancer analysis of 2,863 druggable reveals a wide abundance range identifies biological factors that affect mRNA-protein correlation. Integration proteomic tumors genetic screen cell lines protein overexpression- or hyperactivation-driven dependencies, enabling accurate predictions effective drug Proteogenomic identification synthetic lethality provides strategy target tumor suppressor gene loss. Combining proteogenomic MHC binding prediction prioritizes mutant KRAS peptides as promising neoantigens. Computational shared tumor-associated antigens followed experimental confirmation nominates immunotherapy These analyses, summarized at https://targets.linkedomics.org, form comprehensive landscape peptide targets for companion diagnostics, repurposing, therapy development.

Язык: Английский

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The 2023 Report on the Proteome from the HUPO Human Proteome Project

Journal of Proteome Research, Год журнала: 2024, Номер 23(2), С. 532 - 549

Опубликована: Янв. 17, 2024

Since 2010, the Human Proteome Project (HPP), flagship initiative of Organization (HUPO), has pursued two goals: (1) to credibly identify protein parts list and (2) make proteomics an integral part multiomics studies human health disease. The HPP relies on international collaboration, data sharing, standardized reanalysis MS sets by PeptideAtlas MassIVE-KB using Guidelines for quality assurance, integration curation non-MS neXtProt, plus extensive use antibody profiling carried out Protein Atlas. According neXtProt release 2023-04-18, expression now been detected (PE1) 18,397 19,778 predicted proteins coded in genome (93%). Of these PE1 proteins, 17,453 were with mass spectrometry (MS) accordance 944 a variety methods. number PE2, PE3, PE4 missing stands at 1381. Achieving unambiguous identification 93% encoded from across all chromosomes represents remarkable experimental progress list. Meanwhile, there are several categories that have proved resistant detection regardless protein-based methods used. Additionally some PE1–4 probably should be reclassified PE5, specifically 21 LINC entries ∼30 HERV entries; being addressed present year. Applying wide array biological clinical ensures other omics platforms as reported Biology Disease-driven teams pathology resource pillars. Current positioned transition its Grand Challenge focused determining primary function(s) every itself networks pathways within context

Язык: Английский

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5‐hydroxymethylcytosine features of portal venous blood predict metachronous liver metastases of colorectal cancer and reveal phosphodiesterase 4 as a therapeutic target

Clinical and Translational Medicine, Год журнала: 2025, Номер 15(2)

Опубликована: Фев. 1, 2025

Abstract Metachronous liver metastases (MLM) are characterised by high incidence and mortality in clinical colorectal cancer treatment. Currently traditional methods cannot effectively predict prevent the occurrence of metachronous metastasis cancer. Based on 5hmC‐Seal analysis blood tissue samples, this study found that portal venous was more relevant to tumour gDNA than peripheral blood. We performed a novel epigenetic liquid biopsy strategy using 10 5hmC alterations, accurately distinguish MLM patients from without metastases. Among these phosphodiesterase 4 (PDE4D) highly increased correlated with poor survival. Moreover, our studies demonstrated PDE4D key metastasis‐driven target for drug development. Interfering function significantly repressed Similarly, roflumilast, PDE4 inhibitor chronic obstructive pulmonary disease (COPD) therapy, also inhibits Further indicate blocking can affect CRC invasion through HIF‐1α‐CCN2 pathway. To develop efficient reduce adverse events, we designed several new compounds based 2‐arylbenzofurans discovered lead L11 potent affinity significant suppression In work, provides promising predicting discovers as potential repurposed inhibiting metastasis, which have benefit future. Key points markers derived could promoted via The newly synthesised compound specifically inhibit abolish obvious toxic side effects.

Язык: Английский

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Mass-spectrometry-based proteomics: from single cells to clinical applications

Nature, Год журнала: 2025, Номер 638(8052), С. 901 - 911

Опубликована: Фев. 26, 2025

Язык: Английский

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Enhanced Competition at the Nano–Bio Interface Enables Comprehensive Characterization of Protein Corona Dynamics and Deep Coverage of Proteomes

Advanced Materials, Год журнала: 2022, Номер 34(44)

Опубликована: Авг. 20, 2022

Introducing engineered nanoparticles (NPs) into a biofluid such as blood plasma leads to the formation of selective and reproducible protein corona at particle-protein interface, driven by relationship between protein-NP affinity abundance. This enables scalable systems that leverage protein-nano interactions overcome current limitations deep proteomics in large cohorts. Here importance NP-surface ratio (P/NP) is demonstrated dynamics are modeled, which determine competition proteins for binding. Tuning P/NP significantly modulates composition, enhancing depth precision fully automated NP-based proteomic workflow (Proteograph). By increasing binding on NPs, 1.2-1.7× more with 1% false discovery rate identified surface each NP, up 3× compared standard workflow. Moreover, data suggest plays significant role determining vivo fate nanomaterials biomedical applications. Together, study showcases key design element biomaterials nanomedicine powerful tuning strategy accurate, large-scale studies.

Язык: Английский

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