Integrative genomic and transcriptomic analyses illuminate the ontology of HER2-low breast carcinomas
ConclusionsHLBCs harbor distinct genomic features when compared with HER2-positive and HER2-negative BCs; however, differences across IHC classes were also unveiled thus dissecting the full picture of heterogeneity across HER2-low disease. The HLBC-2E category harbors most distinctive features, whereas HLBC-1 seems superimposable to HER2-negative disease. Further studies are needed to ascertain whether the four genomic-driver classes of the LAURA classification hold prognostic and/or predictive implications. (Source: Genome Medicine)
Source: Genome Medicine - August 29, 2022 Category: Genetics & Stem Cells Source Type: research
ESBL plasmids in Klebsiella pneumoniae: diversity, transmission and contribution to infection burden in the hospital setting
ConclusionsHere, we systematically surveyed ESBL strain and plasmid transmission over 1 year in a single hospital network. Whilst ESBL plasmid transmission events were rare in this setting, they had a significant and sustained impact on the burden of ceftriaxone-resistant and multidrug-resistant infections. If onward transmission of Plasmid A-carrying strains could have been prevente d, this may have reduced the number of opportunities for Plasmid A to transmit and create novel ESBL + strains, as well as reducing overall ESBL infection burden. (Source: Genome Medicine)
Source: Genome Medicine - August 23, 2022 Category: Genetics & Stem Cells Source Type: research
High fluoroquinolone resistance proportions among multidrug-resistant tuberculosis driven by dominant L2 Mycobacterium tuberculosis clones in the Mumbai Metropolitan Region
ConclusionsOur data indicate a drastic increase of FQ resistance, as well as emerging bedaquiline resistance which endangers the success of newly endorsed MDR-TB treatment regimens. Rapid changes in treatment and control strategies are required to contain transmission of highly successful pre-XDR L2 strains in the Mumbai Metropolitan region but presumably also India-wide. (Source: Genome Medicine)
Source: Genome Medicine - August 22, 2022 Category: Genetics & Stem Cells Source Type: research
Clinical implications of host genetic variation and susceptibility to severe or critical COVID-19
AbstractSince the start of the coronavirus disease 2019 (COVID-19) pandemic, important insights have been gained into virus biology and the host factors that modulate the human immune response against severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2). COVID-19 displays a highly variable clinical picture that ranges from asymptomatic disease to lethal pneumonia. Apart from well-established general risk factors such as advanced age, male sex and chronic comorbidities, differences in host genetics have been shown to influence the individual predisposition to develop severe manifestations of COVID-19. These differen...
Source: Genome Medicine - August 19, 2022 Category: Genetics & Stem Cells Source Type: research
High-dimensional investigation of the cerebrospinal fluid to explore and monitor CNS immune responses
AbstractThe cerebrospinal fluid (CSF) features a unique immune cell composition and is in constant contact with the brain borders, thus permitting insights into the brain to diagnose and monitor diseases. Recently, the meninges, which are filled with CSF, were identified as a neuroimmunological interface, highlighting the potential of exploring central nervous system (CNS) immunity by studying CNS border compartments. Here, we summarize how single-cell transcriptomics of such border compartments advance our understanding of neurological diseases, the challenges that remain, and what opportunities novel multi-omic methods...
Source: Genome Medicine - August 17, 2022 Category: Genetics & Stem Cells Source Type: research
Single-cell genomic and transcriptomic landscapes of primary and metastatic colorectal cancer tumors
ConclusionsOur data provides deep insights into how driver mutations interfere with the transcriptomic state of cancer cells in vivo at a single-cell resolution. Our findings offer novel knowledge on metastatic mechanisms as well as potential markers and therapeutic targets for CRC diagnosis and therapy. The high-precision single-cell RNA-seq dataset of matched adjacent normal tissues, primary tumors, and metastases from CRCs may s erve as a rich resource for further studies. (Source: Genome Medicine)
Source: Genome Medicine - August 16, 2022 Category: Genetics & Stem Cells Source Type: research
Crohn ’s disease in endoscopic remission, obesity, and cases of high genetic risk demonstrate overlapping shifts in the colonic mucosal-luminal interface microbiome
ConclusionsObesity, CD in endoscopic remission, and high CD genetic risk have overlapping colonic mucosal-luminal interface (MLI) microbiome features, suggesting a shared microbiome contribution to CD and obesity which may be influenced by genetic factors. Microbial profiling during endoscopic remission predicted Crohn ’s disease behavior and progression, supporting that MLI sampling could offer unique insight into CD pathogenesis and provide novel prognostic biomarkers. (Source: Genome Medicine)
Source: Genome Medicine - August 15, 2022 Category: Genetics & Stem Cells Source Type: research
Crohn ’s disease in endoscopic remission, obesity, and cases of high genetic risk demonstrates overlapping shifts in the colonic mucosal-luminal interface microbiome
ConclusionsObesity, CD in endoscopic remission, and high CD genetic risk have overlapping colonic mucosal-luminal interface (MLI) microbiome features, suggesting a shared microbiome contribution to CD and obesity which may be influenced by genetic factors. Microbial profiling during endoscopic remission predicted Crohn ’s disease behavior and progression, supporting that MLI sampling could offer unique insight into CD pathogenesis and provide novel prognostic biomarkers. (Source: Genome Medicine)
Source: Genome Medicine - August 15, 2022 Category: Genetics & Stem Cells Source Type: research
Diagnostic yield and clinical relevance of expanded genetic testing for cancer patients
ConclusionsCompared to targeted testing approaches, eGT can increase the yield of detection of hereditary cancer predisposition in patients with a range of tumors, allowing opportunities for enhanced surveillance and intervention. The benefits of performing eGT should be weighed against the added number of VUSs identified with this approach. (Source: Genome Medicine)
Source: Genome Medicine - August 15, 2022 Category: Genetics & Stem Cells Source Type: research
Molecular profiling of human non-small cell lung cancer by single-cell RNA-seq
ConclusionsIn summary, our work provides novel insights into the tumor heterogeneity of NSCLC in terms of the identification of prevalent mixed-lineage subpopulations of cancer cells with combined signatures of SCC, ADC, and NET and offers clues for potential treatment strategies in these patients. (Source: Genome Medicine)
Source: Genome Medicine - August 13, 2022 Category: Genetics & Stem Cells Source Type: research
Improved SARS-CoV-2 sequencing surveillance allows the identification of new variants and signatures in infected patients
ConclusionIn conclusion, we have successfully generated an optimized and cost-effective strategy to monitor SARS-CoV-2 genetic variability, without the need of automation. Thus, our approach is suitable for any lab with a benchtop sequencer and a limited budget, allowing an integrated genomic surveillance on premises. Finally, we have also identified a gene expression signature defining SARS-CoV-2 infection in real-world patients ’ upper respiratory ways. (Source: Genome Medicine)
Source: Genome Medicine - August 12, 2022 Category: Genetics & Stem Cells Source Type: research
The telomere maintenance mechanism spectrum and its dynamics in gliomas
ConclusionsThis study suggests that the TMM is dynamic and reflects the plasticity and oncogenicity of tumor cells. Direct measurement of telomerase enzyme activity and evidence of ALT should be considered when defining TMM. An accurate understanding of the TMM in glioma is expected to provide important information for establishing cancer management strategies. (Source: Genome Medicine)
Source: Genome Medicine - August 11, 2022 Category: Genetics & Stem Cells Source Type: research
Clonal evolution in primary breast cancers under sequential epirubicin and docetaxel monotherapy
ConclusionsSequential epirubicin and docetaxel monotherapy caused profound redistribution of smaller subclones in primary breast cancer, while early truncal mutations and major subclones generally persisted through treatment.Trial registrationClinicalTrials.gov,NCT00496795, registered on July 4, 2007. (Source: Genome Medicine)
Source: Genome Medicine - August 11, 2022 Category: Genetics & Stem Cells Source Type: research
Limited evidence for blood eQTLs in human sexual dimorphism
ConclusionsOur results suggest that sex-specific eQTLs in whole blood do not translate to detectable sex-specific trait associations of complex diseases, and vice versa that the observed sex-specific trait associations cannot be explained by sex-specific eQTLs. (Source: Genome Medicine)
Source: Genome Medicine - August 11, 2022 Category: Genetics & Stem Cells Source Type: research
REViewer: haplotype-resolved visualization of read alignments in and around tandem repeats
ConclusionsRead pileup plots generated by REViewer offer an intuitive way to visualize sequencing data in regions containing long repeat expansions. Laboratories can use REViewer and FlipBook to assess the quality of repeat genotype calls as well as to visually detect interruptions or other imperfections in the repeat sequence and the surrounding flanking regions. REViewer and FlipBook are available under open-source licenses athttps://github.com/illumina/REViewer andhttps://github.com/broadinstitute/flipbook respectively. (Source: Genome Medicine)
Source: Genome Medicine - August 11, 2022 Category: Genetics & Stem Cells Source Type: research
