A phenome-wide scan reveals convergence of common and rare variant associations
ConclusionsThe presented framework for the convergence signature has important implications for fine-mapping strategies and drug discovery efforts. In addition, our study provides a blueprint for the expectation from future large-scale whole-genome sequencing (WGS)/WES and sheds methodological light on post-GWAS studies. (Source: Genome Medicine)
Source: Genome Medicine - November 28, 2023 Category: Genetics & Stem Cells Source Type: research
GITR and TIGIT immunotherapy provokes divergent multicellular responses in the tumor microenvironment of gastrointestinal cancers
ConclusionsWe identified novel cellular mechanisms of action of GITR and TIGIT immunotherapy in the patients ’ TME. Unlike the GITR agonist that generated a limited transcriptional response, TIGIT antagonist orchestrated a multicellular response involving CD8 T cells, T follicular helper-like cells, dendritic cells, and regulatory T cells. Our experimental strategy combining single-cell genomics with pre clinical models can successfully identify mechanisms of action of novel immunotherapy agents. Understanding the cellular and transcriptional mechanisms of response or resistance will aid in prioritization of targets and ...
Source: Genome Medicine - November 26, 2023 Category: Genetics & Stem Cells Source Type: research
Massive underrepresentation of Arabs in genomic studies of common disease
AbstractArabs represent 5% of the world population and have a high prevalence of common disease, yet remain greatly underrepresented in genome-wide association studies, where only 1 in 600 individuals are Arab. We highlight the persistent and unaddressed underrepresentation of Arabs in genomic databases and discuss its impact on public health genomics and missed opportunities for biological discovery. (Source: Genome Medicine)
Source: Genome Medicine - November 22, 2023 Category: Genetics & Stem Cells Source Type: research
Loss of p53-DREAM-mediated repression of cell cycle genes as a driver of lymph node metastasis in head and neck cancer
ConclusionsIn HNC, patient survival is affected by multiple biological processes and is strongly influenced by the tumor immune and stromal microenvironments. In contrast, LNM appears to be driven primarily by malignant cell plasticity, characterized by epithelial dedifferentiation coupled with EMT-independent proliferation and stemness. Our findings postulate that LNM is initially caused by loss of p53-DREAM-mediated repression of cell cycle genes during early tumorigenesis. (Source: Genome Medicine)
Source: Genome Medicine - November 17, 2023 Category: Genetics & Stem Cells Source Type: research
The role of admixture in the rare variant contribution to inflammatory bowel disease
ConclusionsEuropean-derived Crohn ’s disease rare variants are even more rare in African Americans and contribute to disease risk mainly due to admixture, which needs to be accounted for when performing cross-ancestry genetic assessments. (Source: Genome Medicine)
Source: Genome Medicine - November 15, 2023 Category: Genetics & Stem Cells Source Type: research
Rapid profiling of Plasmodium parasites from genome sequences to assist malaria control
ConclusionsMalaria-Profiler is a user-friendly tool that can rapidly and accurately predict the geographical regional source and anti-malarial drug resistance profiles across large numbers of samples with WGS data. The software is flexible with modifiable bioinformatic pipelines. For example, it is possible to select the sequencing platform, display specific variants, and customise the format of outputs. With the increasing application of next-generation sequencing platforms onPlasmodium DNA,Malaria-Profiler has the potential to be integrated into point-of-care and surveillance settings, thereby assisting malaria control.M...
Source: Genome Medicine - November 10, 2023 Category: Genetics & Stem Cells Source Type: research
Skeletal muscle regeneration failure in ischemic-damaged limbs is associated with pro-inflammatory macrophages and premature differentiation of satellite cells
ConclusionsCollectively, our research provides the first single-cell transcriptome atlases of skeletal muscle from CLTI patients and a murine CLTI model, emphasizing the crucial role of macrophages and inflammation in regulating muscle regeneration in CLTI through interactions with MuSCs. (Source: Genome Medicine)
Source: Genome Medicine - November 10, 2023 Category: Genetics & Stem Cells Source Type: research
Structural and non-coding variants increase the diagnostic yield of clinical whole genome sequencing for rare diseases
ConclusionsGenome sequencing is increasingly being considered as a first-line genetic test in routine clinical settings and can make a substantial contribution to rapidly identifying a causal aetiology for many patients, shortening their diagnostic odyssey. We have demonstrated that structural, splice site and intronic variants make a significant contribution to diagnostic yield and that comprehensive analysis of the entire genome is essential to maximise the value of clinical genome sequencing. (Source: Genome Medicine)
Source: Genome Medicine - November 9, 2023 Category: Genetics & Stem Cells Source Type: research
Early detection of hepatocellular carcinoma via no end-repair enzymatic methylation sequencing of cell-free DNA and pre-trained neural network
ConclusionsBy combining high-fidelity methylation data from NEEM-seq with the DeepTrace model, our method has great potential for HCC early detection with high sensitivity and specificity, making it potentially suitable for clinical applications.DeepTrace:https://github.com/Bamrock/DeepTrace (Source: Genome Medicine)
Source: Genome Medicine - November 8, 2023 Category: Genetics & Stem Cells Source Type: research
Building blocks for better biorepositories in Africa
ConclusionsBiobanking in low- and middle-income countries by local skilled staff is critical to advance biobanking and genomic research and requires human capacity and resources for global partnerships. Biorepositories can help build human capacity and resources to support biobanking by partnering with researchers. Partnerships can be structured and customized to incorporate document development, ethics, training, mentorship, and pilots to prepare sites to collect, process, store, and transport biospecimens of high quality for future research. (Source: Genome Medicine)
Source: Genome Medicine - November 6, 2023 Category: Genetics & Stem Cells Source Type: research
Annotation of cell types (ACT): a convenient web server for cell type annotation
ConclusionsWe developed a knowledge-based resource and a corresponding method, together with an intuitive graphical web interface, for cell type annotation. We believe that ACT, emerging as a powerful tool for cell type annotation, would be widely used in single-cell research and considerably accelerate the process of cell type identification. (Source: Genome Medicine)
Source: Genome Medicine - November 3, 2023 Category: Genetics & Stem Cells Source Type: research
Multi-scale characterisation of homologous recombination deficiency in breast cancer
ConclusionsWe apply multi-scale approaches to characterise homologous recombination deficiency in breast cancer through the development of mutational and transcriptional signatures. We demonstrate how indels can improve homologous recombination deficiency classification in exome-sequenced breast cancers. Additionally, we demonstrate the heterogeneity of homologous recombination deficiency, especially in relation to BRCA1/2-defect status, and show that indications of this feature can be captured at a single-cell level, enabling further investigations into interactions between DNA repair deficient cells and their tumour micr...
Source: Genome Medicine - November 2, 2023 Category: Genetics & Stem Cells Source Type: research
DeepGAMI: deep biologically guided auxiliary learning for multimodal integration and imputation to improve genotype –phenotype prediction
ConclusionWe demonstrated that DeepGAMI improves phenotype prediction and prioritizes phenotypic features and networks in multiple multimodal datasets in complex brains and brain diseases. Also, it prioritized disease-associated variants, genes, and regulatory networks linked to different phenotypes, providing novel insights into the interpretation of gene regulatory mechanisms. DeepGAMI is open-source and available for general use. (Source: Genome Medicine)
Source: Genome Medicine - October 31, 2023 Category: Genetics & Stem Cells Source Type: research
Bacterial genome-wide association study substantiates papGII of Escherichia coli as a major risk factor for urosepsis
ConclusionsThis study builds on previous work linkingpapGII with invasive infection by showing that it is a major risk factor for progression from UTI to bacteraemia that has diagnostic potential. (Source: Genome Medicine)
Source: Genome Medicine - October 30, 2023 Category: Genetics & Stem Cells Source Type: research
Polygenic risk scores for disease risk prediction in Africa: current challenges and future directions
AbstractEarly identification of genetic risk factors for complex diseases can enable timely interventions and prevent serious outcomes, including mortality. While the genetics underlying many Mendelian diseases have been elucidated, it is harder to predict risk for complex diseases arising from the combined effects of many genetic variants with smaller individual effects on disease aetiology. Polygenic risk scores (PRS), which combine multiple contributing variants to predict disease risk, have the potential to influence the implementation for precision medicine. However, the majority of existing PRS were developed from Eu...
Source: Genome Medicine - October 30, 2023 Category: Genetics & Stem Cells Source Type: research
