Phylogenomic insights into evolutionary trajectories of multidrug resistant S. pneumoniae CC271 over a period of 14 years in China
ConclusionsOur results refined the internal phylogenetic relationship of CC271, showing that the 19F ST271-B and 19A ST320 evolved independently from ST271-A, with different histories and driving forces for their evolution and dissemination in China. (Source: Genome Medicine)
Source: Genome Medicine - July 4, 2023 Category: Genetics & Stem Cells Source Type: research
Whole genome sequencing across clinical trials identifies rare coding variants in GPR68 associated with chemotherapy-induced peripheral neuropathy
ConclusionsOur genetic study provides insight into the impact of low-frequency and rare coding genetic variation on PN risk and suggests that further study ofGPR68 in sensory neurons may yield a therapeutic hypothesis for prevention of CIPN. (Source: Genome Medicine)
Source: Genome Medicine - June 21, 2023 Category: Genetics & Stem Cells Source Type: research
The clinical utility of rapid exome sequencing in a consanguineous population
ConclusionsThis work expands the diversity of environments in which RES has a demonstrable clinical utility. (Source: Genome Medicine)
Source: Genome Medicine - June 21, 2023 Category: Genetics & Stem Cells Source Type: research
ReporTree: a surveillance-oriented tool to strengthen the linkage between pathogen genetic clusters and epidemiological data
ConclusionsIn summary, ReporTree is a pan-pathogen tool for automated and reproducible identification and characterization of genetic clusters that contributes to a sustainable and efficient public health genomics-informed pathogen surveillance. ReporTree is implemented in python 3.8 and is freely available athttps://github.com/insapathogenomics/ReporTree. (Source: Genome Medicine)
Source: Genome Medicine - June 15, 2023 Category: Genetics & Stem Cells Source Type: research
Applications of long-read sequencing to Mendelian genetics
AbstractAdvances in clinical genetic testing, including the introduction of exome sequencing, have uncovered the molecular etiology for many rare and previously unsolved genetic disorders, yet more than half of individuals with a suspected genetic disorder remain unsolved after complete clinical evaluation. A precise genetic diagnosis may guide clinical treatment plans, allow families to make informed care decisions, and permit individuals to participate in N-of-1 trials; thus, there is high interest in developing new tools and techniques to increase the solve rate. Long-read sequencing (LRS) is a promising technology for ...
Source: Genome Medicine - June 14, 2023 Category: Genetics & Stem Cells Source Type: research
Not every estimate counts – evaluation of cell composition estimation approaches in brain bulk tissue data
ConclusionsOur work indicates that cell composition estimation or direct quantification in one tissue sample should not be used as a proxy to the cellular composition of another tissue sample from the same brain region of an individual —even if the samples are directly adjacent. The highly similar outcomes observed among vastly different estimation methods, highlight the need for brain benchmark datasets and better validation approaches. Finally, unless validated through complementary experiments, the interpretation of analyses outcomes based on data confounded by cell composition should be done with great caution, and i...
Source: Genome Medicine - June 7, 2023 Category: Genetics & Stem Cells Source Type: research
Mechanistic insights into the interactions between cancer drivers and the tumour immune microenvironment
ConclusionsOverall, our study delivers a comprehensive resource of TIME drivers, gives mechanistic insights into their immune-regulatory role, and provides an additional framework for patient prioritisation to immunotherapy. The full list of TIME drivers and associated properties are available athttp://www.network-cancer-genes.org. (Source: Genome Medicine)
Source: Genome Medicine - June 5, 2023 Category: Genetics & Stem Cells Source Type: research
Clinical utility of periodic reinterpretation of CNVs of uncertain significance: an 8-year retrospective study
ConclusionsThis study ’s high rate of reinterpretation suggests that CNV interpretation has rapidly evolved since 2010, thanks to the continuous enrichment of available databases. The reinterpreted CNV explained the phenotype for ten patients, leading to optimal genetic counseling. These findings suggest that CNVs sho uld be reinterpreted at least every 2 years. (Source: Genome Medicine)
Source: Genome Medicine - May 23, 2023 Category: Genetics & Stem Cells Source Type: research
Correction: Acetyl-CoA metabolism drives epigenome change and contributes to carcinogenesis risk in fatty liver disease
(Source: Genome Medicine)
Source: Genome Medicine - May 18, 2023 Category: Genetics & Stem Cells Source Type: research
Multi-label transcriptional classification of colorectal cancer reflects tumor cell population heterogeneity
ConclusionsThese results show that CRIS subtypes retain their biological and clinical features even when concomitantly assigned to the same CRC sample. This approach could be potentially extended to other cancer types and classification systems. (Source: Genome Medicine)
Source: Genome Medicine - May 15, 2023 Category: Genetics & Stem Cells Source Type: research
Sex differences in the polygenic architecture of hearing problems in adults
ConclusionsThe results provide many novel insights into the biology and epidemiology of HP in adults. Our sex-specific analyses and transcriptomic associations highlighted molecular pathways that may be targeted for drug development or repurposing. Additionally, the potential causal relationships identified may support novel preventive screening programs to identify individuals at risk. (Source: Genome Medicine)
Source: Genome Medicine - May 11, 2023 Category: Genetics & Stem Cells Source Type: research
High level of complexity and global diversity of the 3q29 locus revealed by optical mapping and long-read sequencing
ConclusionsWe have generated the most comprehensive haplotype map for the 3q29 locus using unaffected individuals, probands with del3q29S or dup3q29S, and available parents, and also determined the deletion breakpoint to be within a 374-bp region in one proband with del3q29S. These results should provide a better understanding of the underlying genetic architecture that contributes to the etiology of del3q29S and dup3q29S. (Source: Genome Medicine)
Source: Genome Medicine - May 10, 2023 Category: Genetics & Stem Cells Source Type: research
Comprehensive de novo mutation discovery with HiFi long-read sequencing
ConclusionsHiFi LRS can now produce the most comprehensive variant dataset obtainable by a single technology in a single laboratory, allowing accurate calling of substitutions, indels, STRs and SVs. The accuracy even allows sensitive calling of DNMs on all variant levels, and also allows for phasing, which helps to distinguish true positive from false positive DNMs. (Source: Genome Medicine)
Source: Genome Medicine - May 8, 2023 Category: Genetics & Stem Cells Source Type: research
Single-molecule methylation profiles of cell-free DNA in cancer with nanopore sequencing
AbstractEpigenetic characterization of cell-free DNA (cfDNA) is an emerging approach for detecting and characterizing diseases such as cancer. We developed a strategy using nanopore-based single-molecule sequencing to measure cfDNA methylomes. This approach generated up to 200 million reads for a single cfDNA sample from cancer patients, an order of magnitude improvement over existing nanopore sequencing methods. We developed a single-molecule classifier to determine whether individual reads originated from a tumor or immune cells. Leveraging methylomes of matched tumors and immune cells, we characterized cfDNA methylomes ...
Source: Genome Medicine - May 3, 2023 Category: Genetics & Stem Cells Source Type: research
Location and condition based reconstruction of colon cancer microbiome from human RNA sequencing data
ConclusionsWe implemented an approach to concurrently analyse clinical and molecular properties of the tumour as well as the composition of the associated microbiome. Our results may improve patient stratification and pave the path for mechanistic studies on microbiota-tumour crosstalk. (Source: Genome Medicine)
Source: Genome Medicine - May 2, 2023 Category: Genetics & Stem Cells Source Type: research
