Background: Proteogenomic characterization and integrative and comparative genomic analysis provide a functional context to annotate genomic abnormalities with prognostic value.
Methods: Here, we analyzed the proteomes and performed whole exome and transcriptome sequencing and single nucleotide polymorphism array profiling for 2 sets of triplet samples comprised of normal colorectal tissue, primary CRC tissue, and synchronous matched liver metastatic tissue.
Results: We identified 112 CNV-mRNA-protein correlated molecules, including up-regulated COL1A2 and BGN associated with prognosis, and four strongest hot spots (chromosomes X, 7, 16 and 1) driving global mRNA abundance variation in CRC liver metastasis. Two sites (DMRTB1 and PARP4) were revealed to frequent mutate only in the liver metastatic cohort and displayed dysregulated protein abundance. Moreover, we confirmed that the mutated peptide number has potential prognosis value and somatic variants displayed increased protein abundance, including high MYH9 and CCT6A expression, with clinical significance.
Conclusions: Our proteogenomic characterization and integrative and comparative genomic analysis provides a new paradigm for understanding human colon and rectal cancer liver metastasis.
Trial Registration: ClinicalTrials, NCT02917707. Registered 28 September 2016, https://clinicaltrials.gov/ct2/show/NCT02917707 .
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http://dx.doi.org/10.1186/s12943-018-0890-1 | DOI Listing |
Alzheimers Dement
December 2024
Northwestern University, Chicago, IL, USA.
Background: Recent advances in Alzheimer's disease (AD) therapeutics involve immunization against amyloid-β (Aβ). Post-mortem brain analysis from the first active Aβ immunotherapy trial indicated clearance of Aβ in some AD patients. Yet, the mechanisms regulating Aβ clearance following immunization remain unknown.
View Article and Find Full Text PDFTrans R Soc Trop Med Hyg
January 2025
Metabolomics and Proteomics Laboratory, Department of Biological Science and Engineering, Maulana Azad National Institute of Technology, Bhopal 462003, India.
Snake venom proteins have long been recognized for their therapeutic potential. Proteogenomic strategies, integrating transcriptomics and proteomics, have emerged as powerful tools for identifying and characterizing venom proteins for the development of novel therapeutic agents. Analytical techniques like mass spectrometry and next-generation sequencing enable comprehensive analysis, identifying key venom components and their variants.
View Article and Find Full Text PDFSci Rep
December 2024
Centro de Pesquisas em Biologia Molecular e Funcional (CPBMF) and Instituto Nacional de Ciência e Tecnologia em Tuberculose (INCT-TB), Escola de Ciências da Saúde e da Vida, Pontifícia Universidade Católica do Rio Grande do Sul (PUCRS), Porto Alegre, Rio Grande do Sul, 90619-900, Brazil.
Tuberculosis remains a burden to this day, due to the rise of multi and extensively drug-resistant bacterial strains. The genome of Mycobacterium tuberculosis (Mtb) strain H37Rv underwent an annotation process that excluded small Open Reading Frames (smORFs), which encode a class of peptides and small proteins collectively known as microproteins. As a result, there is an overlooked part of its proteome that is a rich source of potentially essential, druggable molecular targets.
View Article and Find Full Text PDFMethods Mol Biol
December 2024
The Centre for Crop and Disease Management, Curtin University, Bentley, WA, Australia.
The biochemical makeup of any organism provides insight into key factors regarding its biological functions. These factors can be explored using proteomics, which allows us to obtain a snapshot of the protein content and abundance in an organism, cell type or sub-cellular compartment. Here, we describe proteomic methodologies that can be used to dissect the biochemical mechanism of phytopathogenicity in oomycetes.
View Article and Find Full Text PDFEJHaem
December 2024
Translational Science and Therapeutics Division Fred Hutch Seattle Washington USA.
Introduction: Acute myeloid leukemia (AML) remains one of the deadliest hematopoietic malignancies. A better understanding of the molecular biology governing AML may lead to improved risk stratification and facilitate the development of novel therapies. Proteins are responsible for much of the biology of cells.
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