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
Intra-prostatic tumour evolution, steps in metastatic spread and histogenomic associations revealed by integration of multi-region whole-genome sequencing with histopathological features
ConclusionsOur results link histological transformation with specific genomic alterations and phylogenetic branching. These findings have implications for diagnosis and risk stratification, in addition to providing a rationale for further studies to characterise the genetic changes causally linked to morphological transformation. Our study demonstrates the value of integrating multi-region sequencing with histopathological data to understand tumour evolution and identify mechanisms of prostate cancer spread. (Source: Genome Medicine)
Source: Genome Medicine - February 19, 2024 Category: Genetics & Stem Cells Source Type: research
Detection of a historic reservoir of bedaquiline/clofazimine resistance-associated variants in Mycobacterium tuberculosis
ConclusionsThe presence of a pre-existing reservoir ofMtb strains carrying bedaquiline RAVs prior to its clinical use augments the need for rapid drug susceptibility testing and individualised regimen selection to safeguard the use of bedaquiline in TB care and control. (Source: Genome Medicine)
Source: Genome Medicine - February 19, 2024 Category: Genetics & Stem Cells Source Type: research
Recent advances in polygenic scores: translation, equitability, methods and FAIR tools
AbstractPolygenic scores (PGS) can be used for risk stratification by quantifying individuals ’ genetic predisposition to disease, and many potentially clinically useful applications have been proposed. Here, we review the latest potential benefits of PGS in the clinic and challenges to implementation. PGS could augment risk stratification through combined use with traditional risk factors (demographics, disease-specific risk factors, family history, etc.), to support diagnostic pathways, to predict groups with therapeutic benefits, and to increase the efficiency of clinical trials. However, there exist challenges to max...
Source: Genome Medicine - February 19, 2024 Category: Genetics & Stem Cells Source Type: research
Genome sequencing as a generic diagnostic strategy for rare disease
ConclusionsGS can capture clinically relevant germline variants in a ‘GS-first strategy’ for the majority of clinical indications in a genetics diagnostic lab. (Source: Genome Medicine)
Source: Genome Medicine - February 14, 2024 Category: Genetics & Stem Cells Source Type: research
Implementation of type 1 diabetes genetic risk screening in children in diverse communities: the Virginia PrIMeD project
ConclusionsMinimally invasive saliva sampling implemented using a genetic risk score can identify children at genetic risk of T1D. Consent for autoantibody screening, however, was limited largely due to the SARS-CoV-2 pandemic and need for blood collection. (Source: Genome Medicine)
Source: Genome Medicine - February 14, 2024 Category: Genetics & Stem Cells Source Type: research
Molecular-guided therapy for the treatment of patients with relapsed and refractory childhood cancers: a Beat Childhood Cancer Research Consortium trial
ConclusionsThis trial demonstrated the feasibility, safety, and efficacy of a comprehensive sequencing model to guide personalized therapy for patients with any relapsed/refractory solid malignancy. Personalized therapy was well tolerated, and the clinical benefit rate of 65% in these heavily pretreated populations suggests that this treatment strategy could be an effective option for relapsed and refractory pediatric cancers.Trial registrationClinicalTrials.gov, NCT02162732. Prospectively registered on June 11, 2014. (Source: Genome Medicine)
Source: Genome Medicine - February 12, 2024 Category: Genetics & Stem Cells Source Type: research
Novel genetic markers for chronic kidney disease in a geographically isolated population of Indigenous Australians: Individual and multiple phenotype genome-wide association study
ConclusionsOur study highlights the Tiwi population ’s predisposition towards elevated ACR, and the collection of novel genetic variants associated with kidney function. These associations may prove valuable in the early diagnosis and treatment of renal disease in this underrepresented population. Additionally, further research is needed to compreh ensively validate the functions of the identified variants/genes. (Source: Genome Medicine)
Source: Genome Medicine - February 12, 2024 Category: Genetics & Stem Cells Source Type: research
An atlas of cell-type-specific interactome networks across 44 human tumor types
ConclusionsThis study presented CellNetdb, a comprehensive repository featuring an atlas of cell-type-specific interactome networks across 44 human tumor types. The findings underscore the utility of these networks in delineating the intricacies of tumor microenvironments and advancing the understanding of molecular mechanisms underpinning human tumors. (Source: Genome Medicine)
Source: Genome Medicine - February 12, 2024 Category: Genetics & Stem Cells Source Type: research
Microbial-derived imidazole propionate links the heart failure-associated microbiome alterations to disease severity
ConclusionsOur findings establish a connection between changes in the gut microbiota, the presence, etiology, and severity of HF, and the gut-microbially produced metabolite ImP. While ImP appears promising as a circulating biomarker reflecting gut dysbiosis related to HF, further studies are essential to demonstrate its causal or contributing role in HF pathogenesis.Trial registrationNCT02637167, registered December 22, 2015. (Source: Genome Medicine)
Source: Genome Medicine - February 8, 2024 Category: Genetics & Stem Cells Source Type: research
Rare subclonal sequencing of breast cancers indicates putative metastatic driver mutations are predominately acquired after dissemination
ConclusionsOur results strongly suggest that metastatic driver mutations are sequentially acquired and selected within the same clonal lineage both before, but more commonly after, dissemination from the primary tumor, and that these mutations are biologically consequential. Despite inherent limitations in sampling archival primary tumors, our findings indicate that tumor cells in most patients continue to undergo clinically relevant genomic evolution after their dissemination from the primary tumor. This provides further evidence that metastatic recurrence is a multi-step, mutation-driven process that extends beyond prima...
Source: Genome Medicine - February 6, 2024 Category: Genetics & Stem Cells Source Type: research
Historic methicillin-resistant Staphylococcus aureus: expanding current knowledge using molecular epidemiological characterization of a Swiss legacy collection
ConclusionsThe combined analysis of 1761 historic and contemporary MRSA isolates across more than 50 years uncovered novel STs and allowed us a glimpse into the lineage flux between Swiss-German and international MRSA across time. (Source: Genome Medicine)
Source: Genome Medicine - February 5, 2024 Category: Genetics & Stem Cells Source Type: research
Impact of individual level uncertainty of lung cancer polygenic risk score (PRS) on risk stratification
ConclusionsLung cancer PRS estimates using different methods have modest correlations at the individual level, highlighting the importance of considering individual-level uncertainty when evaluating the practical utility of PRS. (Source: Genome Medicine)
Source: Genome Medicine - February 5, 2024 Category: Genetics & Stem Cells Source Type: research
Pro-inflammatory feedback loops define immune responses to pathogenic Lentivirus infection
ConclusionsOur work presents a model of lentiviral pathogenicity where failures in early viral control mechanisms lead to delayed, sustained, and amplifying pro-inflammatory circuits, which in turn drives disease progression. (Source: Genome Medicine)
Source: Genome Medicine - February 5, 2024 Category: Genetics & Stem Cells Source Type: research
Novel functional insights into ischemic stroke biology provided by the first genome-wide association study of stroke in indigenous Africans
ConclusionsOur findings identify potential roles of regulatory miRNA, intergenic non-coding DNA, and intronic non-coding RNA in the biology of ischemic stroke. These findings reveal new molecular targets that promise to help close the current gaps in accurate African ancestry-based genetic stroke ’s risk prediction and development of new targeted interventions to prevent or treat stroke. (Source: Genome Medicine)
Source: Genome Medicine - February 5, 2024 Category: Genetics & Stem Cells Source Type: research
