Functional genomic analysis delineates regulatory mechanisms of GWAS-identified bipolar disorder risk variants
ConclusionsOur study identifies functional SNPs in some reported risk loci and sheds light on the regulatory mechanisms of BD risk variants. Further functional characterization and mechanistic studies of these functional SNPs and candidate genes will help to elucidate BD pathogenesis and develop new therapeutic approaches and drugs. (Source: Genome Medicine)
Source: Genome Medicine - May 20, 2022 Category: Genetics & Stem Cells Source Type: research

Rapid molecular diagnostics of tuberculosis resistance by targeted stool sequencing
ConclusionstNGS can identify drug resistance from stool provided by tuberculosis patients. This affords the opportunity to obtain critical diagnostic information for tuberculosis patients who struggle to provide respiratory specimens. (Source: Genome Medicine)
Source: Genome Medicine - May 19, 2022 Category: Genetics & Stem Cells Source Type: research

Breast cancer risks associated with missense variants in breast cancer susceptibility genes
ConclusionsThese results will inform risk prediction models and the selection of candidate variants for functional assays and could contribute to the clinical reporting of gene panel testing for breast cancer susceptibility. (Source: Genome Medicine)
Source: Genome Medicine - May 18, 2022 Category: Genetics & Stem Cells Source Type: research

Human liver single nucleus and single  cell RNA sequencing identify a hepatocellular carcinoma-associated cell-type affecting survival
ConclusionsBy integrating liver single cell, single nucleus, and bulk expression data from multiple cohorts we identified a proliferating cell-type (Prol) enriched in HCC tumors, associated with a decreased overall survival, and linked toTP53 andRB1 somatic mutations. (Source: Genome Medicine)
Source: Genome Medicine - May 17, 2022 Category: Genetics & Stem Cells Source Type: research

Single-cell profiling of human dura and meningioma reveals cellular meningeal landscape and insights into meningioma immune response
ConclusionsOur comprehensive investigation of both the immune and non-immune cellular landscapes of human dura and meningioma at single-cell resolution builds upon previously published data in murine models and provides new insight into previously uncharacterized roles of human dura. (Source: Genome Medicine)
Source: Genome Medicine - May 10, 2022 Category: Genetics & Stem Cells Source Type: research

A dynamic single cell-based framework for digital twins to prioritize disease genes and drug targets
ConclusionsWe present a scalable framework for modeling dynamic changes in digital twins, on cellulome- and genome-wide scales, to prioritize UR genes for biomarker and drug discovery. (Source: Genome Medicine)
Source: Genome Medicine - May 6, 2022 Category: Genetics & Stem Cells Source Type: research

Introduction and transmission of SARS-CoV-2 lineage B.1.1.7, Alpha variant, in Denmark
ConclusionsOur findings corroborate early estimates of increased transmissibility of B.1.1.7. Both substantial early expansion when B.1.1.7 was still unmonitored and continuous foreign introductions contributed considerably to case numbers. Finally, our study highlights the benefit of balanced travel restrictions and self-isolation procedures coupled with comprehensive surveillance efforts, to sustain epidemic control in the face of emerging variants. (Source: Genome Medicine)
Source: Genome Medicine - May 4, 2022 Category: Genetics & Stem Cells Source Type: research

Single-cell transcriptomics reveal a unique memory-like NK cell subset that accumulates with ageing and correlates with disease severity in COVID-19
ConclusionsWe identified a unique memory-like NK cell subset that accumulates with ageing and correlates with disease severity in COVID-19. Our results identify memory-like NK2.1 cells as a potential target for developing immunotherapies for infectious diseases and for addressing age-related dysfunctions of the immune system. (Source: Genome Medicine)
Source: Genome Medicine - May 3, 2022 Category: Genetics & Stem Cells Source Type: research

Integrated analysis of single-cell and bulk RNA sequencing data reveals a pan-cancer stemness signature predicting immunotherapy response
ConclusionsWe revealed a robust link between cancer stemness and immunotherapy resistance and developed a promising signature, Stem.Sig, which showed increased performance in comparison to other signatures regarding ICI response prediction. This signature could serve as a competitive tool for patient selection of immunotherapy. Meanwhile, our study potentially paves the way for overcoming immune resistance by targeting stemness-associated genes. (Source: Genome Medicine)
Source: Genome Medicine - April 29, 2022 Category: Genetics & Stem Cells Source Type: research

SvAnna: efficient and accurate pathogenicity prediction of coding and regulatory structural variants in long-read genome sequencing
AbstractStructural variants (SVs) are implicated in the etiology of Mendelian diseases but have been systematically underascertained owing to sequencing technology limitations. Long-read sequencing enables comprehensive detection of SVs, but approaches for prioritization of candidate SVs are needed. Structural variant Annotation and analysis (SvAnna) assesses all classes of SVs and their intersection with transcripts and regulatory sequences, relating predicted effects on gene function with clinical phenotype data. SvAnna places 87% of deleterious SVs in the top ten ranks. The interpretable prioritizations offered by SvAnn...
Source: Genome Medicine - April 28, 2022 Category: Genetics & Stem Cells Source Type: research

Ontology-aware deep learning enables ultrafast and interpretable source tracking among sub-million microbial community samples from hundreds of niches
AbstractThe taxonomic structure of microbial community sample is highly habitat-specific, making source tracking possible, allowing identification of the niches where samples originate. However, current methods face challenges when source tracking is scaled up. Here, we introduce a deep learning method based on the Ontology-aware Neural Network approach, ONN4MST, for large-scale source tracking. ONN4MST outperformed other methods with near-optimal accuracy when source tracking among 125,823 samples from 114 niches. ONN4MST also has a broad spectrum of applications. Overall, this study represents the first model-based metho...
Source: Genome Medicine - April 26, 2022 Category: Genetics & Stem Cells Source Type: research

Large-scale discovery of novel neurodevelopmental disorder-related genes through a unified analysis of single-nucleotide and copy number variants
ConclusionsWe identified dozens of new candidates for NDD genes. Both the methods and the resources developed here will contribute to the further identification of novel NDD-associated genes. (Source: Genome Medicine)
Source: Genome Medicine - April 26, 2022 Category: Genetics & Stem Cells Source Type: research

Anti-SARS-CoV-2 IgA and IgG in human milk after vaccination is dependent on vaccine type and previous SARS-CoV-2 exposure: a longitudinal study
ConclusionsCOVID-19 vaccination induced anti-SARS-CoV-2 IgA and IgG in breast milk with higher levels after the 2nd dose. Levels of anti-SARS-CoV-2 IgA and IgG are dependent on the vaccine type. Further studies are warranted to demonstrate the protective antibody effect against COVID-19 in infants from vaccinated and infected mothers.Trial registrationNCT04751734 (date of registration is on February 12, 2021) (Source: Genome Medicine)
Source: Genome Medicine - April 21, 2022 Category: Genetics & Stem Cells Source Type: research

Preventing disease progression in multiple sclerosis —insights from large real-world cohorts
AbstractMultiple sclerosis is a chronic neuroinflammatory disease with a highly heterogeneous disease course. Preventing lasting disability requires early identification of persons at risk and novel approaches towards patient stratification for personalized treatment decisions. In this comment, we discuss the importance of large datasets of real-world cohorts in order to address this unmet need. (Source: Genome Medicine)
Source: Genome Medicine - April 20, 2022 Category: Genetics & Stem Cells Source Type: research

Variation in targetable genomic alterations in non-small cell lung cancer by genetic ancestry, sex, smoking history, and histology
ConclusionsAmong patients  with NSCLC, there was significant variability in the prevalence of targetable genomic alterations according to genetic ancestry, histology, and smoking. Patients with LUSC and LCLC have 5% rates of targetable alterations supporting consideration for sequencing in those subtypes. (Source: Genome Medicine)
Source: Genome Medicine - April 15, 2022 Category: Genetics & Stem Cells Source Type: research