Conserved methylation signatures associate with the tumor immune microenvironment and immunotherapy response
ConclusionsOur findings demonstrated that the methylation signatures of distinct biological processes are associated with immune activity in the cancer microenvironment and predict immunotherapy response. (Source: Genome Medicine)
Source: Genome Medicine - April 2, 2024 Category: Genetics & Stem Cells Source Type: research
Full-spectral genome analysis of natural killer/T cell lymphoma highlights impacts of genome instability in driving its progression
ConclusionsThe striking differences underlying the mutational landscapes between the primary and relapsed/refractory NKTCL patients highlight the importance of genomic instability in driving the progression of NKTCL. Our newly proposed molecular subtyping system is valuable in assisting patient stratification and novel treatment design towards a better prognosis in the age of precision medicine. (Source: Genome Medicine)
Source: Genome Medicine - April 2, 2024 Category: Genetics & Stem Cells Source Type: research
Glioblastoma-instructed microglia transition to heterogeneous phenotypic states with phagocytic and dendritic cell-like features in patient tumors and patient-derived orthotopic xenografts
ConclusionsOur data provide novel insights into the phenotypic adaptation of the heterogeneous TME instructed by GBM tumors. We show the key role of microglial phenotypic states in supporting GBM tumor growth and response to treatment. Our data place PDOXs as relevant models to assess the functionality of the TME and changes in the GBM ecosystem upon treatment.Graphical Abstract (Source: Genome Medicine)
Source: Genome Medicine - April 2, 2024 Category: Genetics & Stem Cells Source Type: research
Leveraging new methods for comprehensive characterization of mitochondrial DNA in esophageal squamous cell carcinoma
ConclusionsOur new frameworks promote the characterization of mtDNA features, which enables the elucidation of the landscapes and roles of mtDNA in ESCC essential for extending the current understanding of ESCC etiology. dMTLV and fNUMT are freely available fromhttps://github.com/sunnyzxh/dMTLV andhttps://github.com/sunnyzxh/fNUMT, respectively. (Source: Genome Medicine)
Source: Genome Medicine - April 2, 2024 Category: Genetics & Stem Cells Source Type: research
Race-specific coregulatory and transcriptomic profiles associated with DNA methylation and androgen receptor in prostate cancer
ConclusionsOur study reveals unique signaling networks underlying prostate cancer biology in AA and EA men, offering potential insights for clinical management strategies tailored to specific racial groups. Targeting AR and associated pathways could be particularly beneficial in addressing the disparities observed in prostate cancer outcomes in the context of AA and EA men. Further investigation into these identified pathways may lead to the development of personalized therapeutic approaches to improve outcomes for prostate cancer patients across different racial backgrounds. (Source: Genome Medicine)
Source: Genome Medicine - April 2, 2024 Category: Genetics & Stem Cells Source Type: research
Deep learning in cancer genomics and histopathology
AbstractHistopathology and genomic profiling are cornerstones of precision oncology and are routinely obtained for patients with cancer. Traditionally, histopathology slides are manually reviewed by highly trained pathologists. Genomic data, on the other hand, is evaluated by engineered computational pipelines. In both applications, the advent of modern artificial intelligence methods, specifically machine learning (ML) and deep learning (DL), have opened up a fundamentally new way of extracting actionable insights from raw data, which could augment and potentially replace some aspects of traditional evaluation workflows. ...
Source: Genome Medicine - March 27, 2024 Category: Genetics & Stem Cells Source Type: research
Systematic immune cell dysregulation and molecular subtypes revealed by single-cell RNA-seq of subjects with type 1 diabetes
ConclusionsOur study reveals a surprisingly strong systemic dimension at the level of immune cell network in T1DM, defines disease-relevant molecular subtypes, and has the potential to guide non-invasive test development and patient stratification. (Source: Genome Medicine)
Source: Genome Medicine - March 27, 2024 Category: Genetics & Stem Cells Source Type: research
Diversity of CFTR variants across ancestries characterized using 454,727 UK biobank whole exome sequences
ConclusionsWe leveraged the UKBB database to comprehensively characterize the broad spectrum ofCFTR variants across ancestries. The detection of over 4000CFTR variants, including several ancestry-specific and uncharacterizedCFTR variants, warrants the need for further characterization of their functional and clinical relevance. Overall, the presentation of classical CF phenotypes seen in non-CF diagnosed participants with more than one CF-causing variant indicates that they may benefit from current CFTR modulator therapies. (Source: Genome Medicine)
Source: Genome Medicine - March 21, 2024 Category: Genetics & Stem Cells Source Type: research
Predicting the presence of coronary plaques featuring high-risk characteristics using polygenic risk scores and targeted proteomics in patients with suspected coronary artery disease
ConclusionsIn patients with suspected CAD, incorporating genetic data with either clinical or proteomic data improves the prediction of high-risk plaque presence.Trial registrationhttps://clinicaltrials.gov/ct2/show/NCT02264717 (September 2014). (Source: Genome Medicine)
Source: Genome Medicine - March 20, 2024 Category: Genetics & Stem Cells Source Type: research
scDrugPrio: a framework for the analysis of single-cell transcriptomics to address multiple problems in precision medicine in immune-mediated inflammatory diseases
ConclusionsWe propose a computational framework, scDrugPrio, for drug prioritisation based on scRNA-seq of IMID disease. Application to individual patients indicates scDrugPrio ’s potential for personalised network-based drug screening on cellulome-, genome-, and drugome-wide scales. For this purpose, we made scDrugPrio into an easy-to-use R package (https://github.com/SDTC-CPMed/scDrugPrio). (Source: Genome Medicine)
Source: Genome Medicine - March 20, 2024 Category: Genetics & Stem Cells Source Type: research
Ethnic variations in metabolic syndrome components and their associations with the gut microbiota: the HELIUS study
ConclusionsThe occurrence of MetS characteristics among ethnicities is heterogeneous. Both ethnic-independent and ethnic-specific associations were identified between the gut microbiota and MetS outcomes. Across multiple ethnicities, a one-size-fits-all approach may thus be reconsidered in regard to both the definition and/or treatment of MetS and its relation to the gut microbiota. (Source: Genome Medicine)
Source: Genome Medicine - March 20, 2024 Category: Genetics & Stem Cells Source Type: research
The exceptions that prove the rule —a historical view of bedaquiline susceptibility
AbstractIn the accompanying study, Nimmo and colleagues estimated the dates of emergence of mutations inmmpR5 (Rv0678), the most important resistance gene to the anti-tuberculosis drug bedaquiline, in over 3500 geographically diverseMycobacterium tuberculosis genomes. This provided important insights to improve the design and analysis of clinical trials, as well as the World Health Organization catalogue of resistance mutations, the global reference for interpreting genotypic antimicrobial susceptibility testing results. (Source: Genome Medicine)
Source: Genome Medicine - March 13, 2024 Category: Genetics & Stem Cells Source Type: research
Untargeted metabolomic profiling reveals molecular signatures associated with type 2 diabetes in Nigerians
ConclusionsWe demonstrate that metabolomic dysregulation associated with T2D in Nigerians affects multiple processes, including glycolysis, free fatty acid and bile metabolism, and branched chain amino acid catabolism. Our study replicated previous findings in other populations and identified a metabolic signature that could be used as a biomarker panel of T2D risk and glycemic control thus enhancing our knowledge of molecular pathophysiologic changes in T2D. The metabolomics dataset generated in this study represents an invaluable addition to publicly available multi-omics data on understudied African ancestry populations...
Source: Genome Medicine - March 5, 2024 Category: Genetics & Stem Cells Source Type: research
Long-term beneficial effect of faecal microbiota transplantation on colonisation of multidrug-resistant bacteria and resistome abundance in patients with recurrent Clostridioides difficile infection
ConclusionsTaken together, we hypothesise that FMT restores the gut microbiota to a composition that is closer to the composition of healthy donors, and potential pathogens are either lost or decreased to very low abundances. This process, however, does not end in the days following FMT. It may take months for the gut microbiome to re-establish a balanced state. Even though a reservoir of resistance genes remains, a notable part of which on plasmids, FMT decreases the total load of resistance genes. (Source: Genome Medicine)
Source: Genome Medicine - February 28, 2024 Category: Genetics & Stem Cells Source Type: research
Deciphering cancer cell state plasticity with single-cell genomics and artificial intelligence
AbstractCancer stem cell plasticity refers to the ability of tumour cells to dynamically switch between states —for example, from cancer stem cells to non-cancer stem cell states. Governed by regulatory processes, cells transition through a continuum, with this transition space often referred to as a cell state landscape. Plasticity in cancer cell states leads to divergent biological behaviours, with certa in cell states, or state transitions, responsible for tumour progression and therapeutic response. The advent of single-cell assays means these features can now be measured for individual cancer cells and at scale. How...
Source: Genome Medicine - February 26, 2024 Category: Genetics & Stem Cells Source Type: research
