Genomic analysis of the international high-risk clonal lineage Klebsiella pneumoniae sequence type 395
ConclusionsTo the best of our knowledge, this is the first study that investigated a large international collection ofK. pneumoniae ST395 genomes and elucidated phylogenetics and detailed genomic characteristics of this emerging high-risk clonal lineage. (Source: Genome Medicine)
Source: Genome Medicine - February 13, 2023 Category: Genetics & Stem Cells Source Type: research
Pervasiveness of HLA allele-specific expression loss across tumor types
ConclusionsTogether, our results highlight the prevalence of HLA-I ASE loss and provide initial evidence of its clinical significance in cancer prognosis and immunotherapy treatment. (Source: Genome Medicine)
Source: Genome Medicine - February 9, 2023 Category: Genetics & Stem Cells Source Type: research
The genomic landscape of rare disorders in the Middle East
ConclusionsEarly access to genomic diagnostics for patients with suspected rare disorders in the Middle East is likely to improve clinical outcomes while driving gene discovery in this genetically underrepresented population. (Source: Genome Medicine)
Source: Genome Medicine - January 27, 2023 Category: Genetics & Stem Cells Source Type: research
Aggregation tests identify new gene associations with breast cancer in populations with diverse ancestry
ConclusionsUsing extended gene-based aggregation tests including coding and regulatory variation, we report identification of plausible target genes for previously identified single-marker associations with BC as well as the discovery of novel genes implicated in BC development. Including multi ancestral cohorts in this study enabled the identification of otherwise missed disease associations asESR1 (P = 1.31 × 10−5), demonstrating the importance of diversifying study cohorts. (Source: Genome Medicine)
Source: Genome Medicine - January 26, 2023 Category: Genetics & Stem Cells Source Type: research
The neuroimmune axis of Alzheimer ’s disease
AbstractAlzheimer ’s disease (AD) is a genetically complex and heterogeneous disorder with multifaceted neuropathological features, including β-amyloid plaques, neurofibrillary tangles, and neuroinflammation. Over the past decade, emerging evidence has implicated both beneficial and pathological roles for innate i mmune genes and immune cells, including peripheral immune cells such as T cells, which can infiltrate the brain and either ameliorate or exacerbate AD neuropathogenesis. These findings support a neuroimmune axis of AD, in which the interplay of adaptive and innate immune systems inside and outside t he brain c...
Source: Genome Medicine - January 26, 2023 Category: Genetics & Stem Cells Source Type: research
Risk assessment for colorectal cancer via polygenic risk score and lifestyle exposure: a large-scale association study of East Asian and European populations
ConclusionsIn summary, we systemically constructed an EAS-EUR PRS to effectively stratify colorectal cancer risk, which highlighted its clinical implication among diverse ancestries. Importantly, these findings also supported that a healthy lifestyle could reduce the genetic impact on incident colorectal cancer. (Source: Genome Medicine)
Source: Genome Medicine - January 24, 2023 Category: Genetics & Stem Cells Source Type: research
Large-scale genomic analysis of global Klebsiella pneumoniae plasmids reveals multiple simultaneous clusters of carbapenem-resistant hypervirulent strains
ConclusionsOur analysis demonstrates the importance of plasmid analysis in the monitoring of carbapenem-resistant and hypervirulent strains of Kp. With the growing adoption of omics-based technologies for clinical and surveillance applications, including in geographical regions with gaps in data and knowledge (e.g. sub-Saharan Africa), the identification of the spread of AMR will inform infection control globally. (Source: Genome Medicine)
Source: Genome Medicine - January 19, 2023 Category: Genetics & Stem Cells Source Type: research
Single-cell transcriptomics reveals a mechanosensitive injury signaling pathway in early diabetic nephropathy
ConclusionsOverall, our study presents a comprehensive single-cell transcriptomic landscape of early DN, highlighting mechanosensitive signaling pathways as novel targets of diabetic glomerulopathy. (Source: Genome Medicine)
Source: Genome Medicine - January 10, 2023 Category: Genetics & Stem Cells Source Type: research
The gut microbiota in multiple sclerosis varies with disease activity
ConclusionsConsiderable aberrations are present in the gut microbiota of patients with multiple sclerosis that are directly associated with blood biomarkers of inflammation, and in treatment-na ïve cases bacterial richness is positively associated with disease activity. Yet, the finding of two symbiotic bacterial species in non-disease-active cases that produce favorable immune-modulating compounds provides a rationale for testing these bacteria as adjunct therapeutics in future clinical trials. (Source: Genome Medicine)
Source: Genome Medicine - January 5, 2023 Category: Genetics & Stem Cells Source Type: research
A one-year genomic investigation of Escherichia coli epidemiology and nosocomial spread at a large US healthcare network
ConclusionBy coupling in-depth genomic characterization with a complete sampling of clinical isolates for a full year, this study provides a rare and contemporary survey on the epidemiology and spread ofE. coli in a large US healthcare network. While surveillance and infection control efforts often focus on ESBL and MDR lineages, our findings reveal that non-MDR isolates represent a large burden of infections, including those of predicted nosocomial origins. This increased awareness is key for implementing effective WGS-based surveillance as a routine technology for infection control. (Source: Genome Medicine)
Source: Genome Medicine - December 30, 2022 Category: Genetics & Stem Cells Source Type: research
Neutralization sensitivity, fusogenicity, and infectivity of Omicron subvariants
ConclusionsThese findings have important public health implications and highlight the importance of repeated exposure to SARS-CoV-2 antigens to broaden the neutralizing antibody response against Omicron subvariants. (Source: Genome Medicine)
Source: Genome Medicine - December 29, 2022 Category: Genetics & Stem Cells Source Type: research
The role of genetic testing in diagnosis and care of inherited cardiac conditions in a specialised multidisciplinary clinic
ConclusionsResearch-focused efforts can increase the diagnostic yield by up to 5%. Where a variant is identified, this will have clinical utility beyond family screening in 13%. We demonstrate the value of genomics in reaching an overall diagnosis and highlight inequities based on ancestry. Acknowledging our incomplete understanding of disease phenotypes, we propose a framework for prioritising likely monogenic cases to solve their underlying cause of disease. (Source: Genome Medicine)
Source: Genome Medicine - December 28, 2022 Category: Genetics & Stem Cells Source Type: research
Post-vaccine epidemiology of serotype 3 pneumococci identifies transformation inhibition through prophage-driven alteration of a non-coding RNA
ConclusionThis interference with the quorum sensing needed to induce competence reduces the risk of the prophage being deleted by homologous recombination. Hence the selfish prophage-driven alteration of a regulatory RNA limits cell-cell communication and horizontal gene transfer, complicating the interpretation of post-vaccine population dynamics. (Source: Genome Medicine)
Source: Genome Medicine - December 20, 2022 Category: Genetics & Stem Cells Source Type: research
Spatiotemporal evolution of the clear cell renal cell carcinoma microenvironment links intra-tumoral heterogeneity to immune escape
ConclusionsThese results argue that genetic and immune heterogeneity jointly co-evolve and influence response to ICI in ccRCC. Our findings have implications for future biomarker development for ICI response across ccRCC and other solid tumors and highlight important features of tumor evolution under ICI treatment.Trial registrationThe study was registered on ClinicalTrial.gov (NCT02595918) on November 4, 2015. (Source: Genome Medicine)
Source: Genome Medicine - December 19, 2022 Category: Genetics & Stem Cells Source Type: research
Multi-region sequencing with spatial information enables accurate heterogeneity estimation and risk stratification in liver cancer
ConclusionsThis study provides new insights into the complex phenotypes of HCC and may serve as a guide for future studies in this field. (Source: Genome Medicine)
Source: Genome Medicine - December 16, 2022 Category: Genetics & Stem Cells Source Type: research
