-
Molecular & Cellular Proteomics : MCP Nov 2020MS-based proteome profiling has become increasingly comprehensive and quantitative, yet a persistent shortcoming has been the relatively large samples required to... (Review)
Review
MS-based proteome profiling has become increasingly comprehensive and quantitative, yet a persistent shortcoming has been the relatively large samples required to achieve an in-depth measurement. Such bulk samples, typically comprising thousands of cells or more, provide a population average and obscure important cellular heterogeneity. Single-cell proteomics capabilities have the potential to transform biomedical research and enable understanding of biological systems with a new level of granularity. Recent advances in sample processing, separations and MS instrumentation now make it possible to quantify >1000 proteins from individual mammalian cells, a level of coverage that required an input of thousands of cells just a few years ago. This review discusses important factors and parameters that should be optimized across the workflow for single-cell and other low-input measurements. It also highlights recent developments that have advanced the field and opportunities for further development.
Topics: Cells, Cultured; Chromatography, Liquid; Humans; Mass Spectrometry; Proteome; Proteomics; RNA-Seq; Single-Cell Analysis
PubMed: 32847821
DOI: 10.1074/mcp.R120.002234 -
Biomolecules May 2021Homocysteine is a non-proteinogenic sulfhydryl-containing amino acid derived from methionine and is a homologue of cysteine [...].
Homocysteine is a non-proteinogenic sulfhydryl-containing amino acid derived from methionine and is a homologue of cysteine [...].
Topics: Animals; Biochemistry; Disease; Homocysteine; Humans; Molecular Biology
PubMed: 34063494
DOI: 10.3390/biom11050737 -
Cancer Cell Mar 2022Acute myeloid leukemia (AML) is an aggressive blood cancer with a poor prognosis. We report a comprehensive proteogenomic analysis of bone marrow biopsies from 252...
Acute myeloid leukemia (AML) is an aggressive blood cancer with a poor prognosis. We report a comprehensive proteogenomic analysis of bone marrow biopsies from 252 uniformly treated AML patients to elucidate the molecular pathophysiology of AML in order to inform future diagnostic and therapeutic approaches. In addition to in-depth quantitative proteomics, our analysis includes cytogenetic profiling and DNA/RNA sequencing. We identify five proteomic AML subtypes, each reflecting specific biological features spanning genomic boundaries. Two of these proteomic subtypes correlate with patient outcome, but none is exclusively associated with specific genomic aberrations. Remarkably, one subtype (Mito-AML), which is captured only in the proteome, is characterized by high expression of mitochondrial proteins and confers poor outcome, with reduced remission rate and shorter overall survival on treatment with intensive induction chemotherapy. Functional analyses reveal that Mito-AML is metabolically wired toward stronger complex I-dependent respiration and is more responsive to treatment with the BCL2 inhibitor venetoclax.
Topics: Humans; Leukemia, Myeloid, Acute; Proteogenomics; Proteomics
PubMed: 35245447
DOI: 10.1016/j.ccell.2022.02.006 -
Nucleic Acids Research Jan 2022The Human Metabolome Database or HMDB (https://hmdb.ca) has been providing comprehensive reference information about human metabolites and their associated biological,...
The Human Metabolome Database or HMDB (https://hmdb.ca) has been providing comprehensive reference information about human metabolites and their associated biological, physiological and chemical properties since 2007. Over the past 15 years, the HMDB has grown and evolved significantly to meet the needs of the metabolomics community and respond to continuing changes in internet and computing technology. This year's update, HMDB 5.0, brings a number of important improvements and upgrades to the database. These should make the HMDB more useful and more appealing to a larger cross-section of users. In particular, these improvements include: (i) a significant increase in the number of metabolite entries (from 114 100 to 217 920 compounds); (ii) enhancements to the quality and depth of metabolite descriptions; (iii) the addition of new structure, spectral and pathway visualization tools; (iv) the inclusion of many new and much more accurately predicted spectral data sets, including predicted NMR spectra, more accurately predicted MS spectra, predicted retention indices and predicted collision cross section data and (v) enhancements to the HMDB's search functions to facilitate better compound identification. Many other minor improvements and updates to the content, the interface, and general performance of the HMDB website have also been made. Overall, we believe these upgrades and updates should greatly enhance the HMDB's ease of use and its potential applications not only in human metabolomics but also in exposomics, lipidomics, nutritional science, biochemistry and clinical chemistry.
Topics: Databases, Genetic; Humans; Lipidomics; Mass Spectrometry; Metabolome; Metabolomics; User-Computer Interface
PubMed: 34986597
DOI: 10.1093/nar/gkab1062 -
Cancer Cell Aug 2023The National Cancer Institute's Clinical Proteomic Tumor Analysis Consortium (CPTAC) investigates tumors from a proteogenomic perspective, creating rich multi-omics... (Review)
Review
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 tumors in 10 cohorts to create a cohesive and powerful dataset for scientific discovery. We outline efforts by the CPTAC pan-cancer working group in data harmonization, data dissemination, and computational resources for aiding biological discoveries. We also discuss challenges for multi-omics data integration and analysis, specifically the unique challenges of working with both nucleotide sequencing and mass spectrometry proteomics data.
Topics: Humans; Proteogenomics; Proteomics; Genomics; Neoplasms; Gene Expression Profiling
PubMed: 37582339
DOI: 10.1016/j.ccell.2023.06.009 -
Survey of Ophthalmology 2022The human tear film is at the interface between the ocular surface and the external environment. Although investigation has been hindered by its small volume,... (Review)
Review
The human tear film is at the interface between the ocular surface and the external environment. Although investigation has been hindered by its small volume, improvements in preanalytical and analytical methods have allowed the omics approach to represent an innovative biomarker search strategy. There is still a significant lack of standardization, representing a barrier for performing between-studies comparisons and transferring experimental findings into clinical use and trials. We summarize the preanalytical and analytical procedures, describe the biomarkers that can be found using the metabo-lipidomics approach, and provide our expert opinion for omics investigations in human tears. For this systematic review of 38 studies, we searched PubMed by combining Boolean operators with the following keywords: tear, metabolomic, lipidomic, -omics. The human tear metabo-lipidome has been well-characterized in normal individuals using high-resolution liquid chromatography coupled with mass spectrometry. Lipid and metabolite profiles were influenced by ocular (e.g., dry eye disorders; Meibomian gland dysfunction; contact lens wear; glaucoma; keratoconus; pterygium) and systemic conditions (e.g., multiple sclerosis). Investigating the tear metabo-lipidome could improve our understanding of the pathogenesis of both ocular and systemic diseases, but also provide diagnostic as well as prognostic biomarkers.
Topics: Biomarkers; Dry Eye Syndromes; Humans; Lipidomics; Meibomian Glands; Metabolomics; Tears
PubMed: 35093405
DOI: 10.1016/j.survophthal.2022.01.010 -
Cell Feb 2024Despite the successes of immunotherapy in cancer treatment over recent decades, less than <10%-20% cancer cases have demonstrated durable responses from immune...
Despite the successes of immunotherapy in cancer treatment over recent decades, less than <10%-20% cancer cases have demonstrated durable responses from immune checkpoint blockade. To enhance the efficacy of immunotherapies, combination therapies suppressing multiple immune evasion mechanisms are increasingly contemplated. To better understand immune cell surveillance and diverse immune evasion responses in tumor tissues, we comprehensively characterized the immune landscape of more than 1,000 tumors across ten different cancers using CPTAC pan-cancer proteogenomic data. We identified seven distinct immune subtypes based on integrative learning of cell type compositions and pathway activities. We then thoroughly categorized unique genomic, epigenetic, transcriptomic, and proteomic changes associated with each subtype. Further leveraging the deep phosphoproteomic data, we studied kinase activities in different immune subtypes, which revealed potential subtype-specific therapeutic targets. Insights from this work will facilitate the development of future immunotherapy strategies and enhance precision targeting with existing agents.
Topics: Humans; Combined Modality Therapy; Genomics; Neoplasms; Proteogenomics; Proteomics; Tumor Escape
PubMed: 38359819
DOI: 10.1016/j.cell.2024.01.027 -
Signal Transduction and Targeted Therapy Mar 2023Tumour cells have exquisite flexibility in reprogramming their metabolism in order to support tumour initiation, progression, metastasis and resistance to therapies.... (Review)
Review
Tumour cells have exquisite flexibility in reprogramming their metabolism in order to support tumour initiation, progression, metastasis and resistance to therapies. These reprogrammed activities include a complete rewiring of the bioenergetic, biosynthetic and redox status to sustain the increased energetic demand of the cells. Over the last decades, the cancer metabolism field has seen an explosion of new biochemical technologies giving more tools than ever before to navigate this complexity. Within a cell or a tissue, the metabolites constitute the direct signature of the molecular phenotype and thus their profiling has concrete clinical applications in oncology. Metabolomics and fluxomics, are key technological approaches that mainly revolutionized the field enabling researchers to have both a qualitative and mechanistic model of the biochemical activities in cancer. Furthermore, the upgrade from bulk to single-cell analysis technologies provided unprecedented opportunity to investigate cancer biology at cellular resolution allowing an in depth quantitative analysis of complex and heterogenous diseases. More recently, the advent of functional genomic screening allowed the identification of molecular pathways, cellular processes, biomarkers and novel therapeutic targets that in concert with other technologies allow patient stratification and identification of new treatment regimens. This review is intended to be a guide for researchers to cancer metabolism, highlighting current and emerging technologies, emphasizing advantages, disadvantages and applications with the potential of leading the development of innovative anti-cancer therapies.
Topics: Humans; Metabolomics; Neoplasms; Energy Metabolism; Biomarkers
PubMed: 36949046
DOI: 10.1038/s41392-023-01380-0 -
International Journal of Molecular... Jun 2022In the Special Issue entitled "Orchid Biochemistry", researchers explored the biochemistry and molecular mechanisms of pigment formation, flower scent, bioactive...
In the Special Issue entitled "Orchid Biochemistry", researchers explored the biochemistry and molecular mechanisms of pigment formation, flower scent, bioactive compounds, plant-microbial interaction, as well as aspects of biotechnology, and these studies have greatly enriched the understanding in the field of orchid biology [...].
Topics: Biochemistry; Biotechnology; Flowers; Odorants; Orchidaceae
PubMed: 35743269
DOI: 10.3390/ijms23126823 -
Cells Apr 2022Platelets may be pivotal mediators of the thrombotic and coagulopathic complications of preeclampsia (PE), linking inflammation and thrombosis with endothelial and...
Platelets may be pivotal mediators of the thrombotic and coagulopathic complications of preeclampsia (PE), linking inflammation and thrombosis with endothelial and vascular dysfunction. Both PE and gestational hypertension (GH) fall within the spectrum of hypertensive complications of pregnancy, with GH being a risk factor for preeclampsia. However, it is unclear what biomarkers distinguish PE from GH. Using a discovery size cohort, we aimed to characterize specific plasma and platelet thrombo-inflammatory drivers indicative of PE and differentiate PE from GH. We performed multiplex immunoassays, platelet and plasma quantitative proteomics and metabolomics of PE patients, comparing with non-pregnant (NP), healthy pregnant controls (PC) and GH participants. The expression pattern of plasma proteins and metabolites in PE/GH platelets was distinct from that of NP and PC. Whilst procoagulation in PC may be fibrinogen driven, inter-alpha-trypsin inhibitors ITIH2 and ITIH3 are likely mediators of thrombo-inflammation in GH and PE, and fibronectin and S100A8/9 may be major procoagulant agonists in PE only. Also enriched in PE were CCL1 and CCL27 plasma cytokines, and the platelet leucine-rich repeat-containing protein 27 and 42 (LRRC27/42), whose effects on platelets were explored using STRING analysis. Through protein-protein interactions analysis, we generated a new hypothesis for platelets' contribution to the thrombo-inflammatory states of preeclampsia.
Topics: Blood Platelets; Female; Humans; Hypertension, Pregnancy-Induced; Inflammation; Metabolomics; Pre-Eclampsia; Pregnancy; Proteomics
PubMed: 35455936
DOI: 10.3390/cells11081256