African-specific alleles modify risk for asthma at the 17q12-q21 locus in African Americans
ConclusionsPreviously unknown genetic variation at the 17q12-21 childhood-onset asthma locus contributes to asthma severity in individuals with African ancestries. We suggest that many other population-specific variants that have not been discovered in GWAS contribute to the genetic risk for asthma and other common diseases. (Source: Genome Medicine)
Source: Genome Medicine - September 29, 2022 Category: Genetics & Stem Cells Source Type: research
Transcriptional signatures of the BCL2 family for individualized acute myeloid leukaemia treatment
ConclusionsThis study proposes BFSigs as a biomarker for the effective selection of apoptosis targeting treatments and cancer pathways to co-target in AML. (Source: Genome Medicine)
Source: Genome Medicine - September 28, 2022 Category: Genetics & Stem Cells Source Type: research
Single-cell RNA transcriptome analysis of CNS immune cells reveals CXCL16/CXCR6 as maintenance factors for tissue-resident T cells that drive synapse elimination
ConclusionsWe provide a comprehensive assessment of the role of CXCL16/CXCR6 as an interaction link between microglia and CD8+ T cells that maintains forebrain TRM cells, microglial and astrocyte activation, and ongoing synapse elimination in virally recovered animals. We also show that therapeutic targeting of CXCL16 in mice during recovery may reduce CNS CD8+ TRM cells. (Source: Genome Medicine)
Source: Genome Medicine - September 24, 2022 Category: Genetics & Stem Cells Source Type: research
Intratumor heterogeneity and T cell exhaustion in primary CNS lymphoma
ConclusionsMalignant B cells in PCNSL show transcriptional and spatial intratumor heterogeneity. T cell exhaustion is frequent in the PCNSL microenvironment, co-localizes with malignant cells, and highlights the potential of personalized treatments. (Source: Genome Medicine)
Source: Genome Medicine - September 24, 2022 Category: Genetics & Stem Cells Source Type: research
Longitudinal multi-omics analysis identifies early blood-based predictors of anti-TNF therapy response in inflammatory bowel disease
ConclusionsIntegrative multi-omics analysis reveals early shifts of gene expression and DNA methylation as predictors for efficient response to anti-TNF treatment. Lack of such signatures might be used to identify patients with IBD unlikely to benefit from TNF antagonists at an early time point. (Source: Genome Medicine)
Source: Genome Medicine - September 24, 2022 Category: Genetics & Stem Cells Source Type: research
Correction: Rapid molecular diagnostics of tuberculosis resistance by targeted stool sequencing
(Source: Genome Medicine)
Source: Genome Medicine - September 20, 2022 Category: Genetics & Stem Cells Source Type: research
Elucidating the diversity of malignant mesenchymal states in glioblastoma by integrative analysis
ConclusionsDiverse MES states occur in glioblastoma. These states share a subset of core genes but differ primarily in their association with hypoxia vs. astrocytic expression programs, and with immune suppression vs. activation, respectively. (Source: Genome Medicine)
Source: Genome Medicine - September 19, 2022 Category: Genetics & Stem Cells Source Type: research
A novel molecular signature identifies mixed subtypes in renal cell carcinoma with poor prognosis and independent response to immunotherapy
ConclusionSwitching from categorical to continuous subtype classification across most frequent RCC subtypes enables outcome prediction and fosters personalized treatment strategies. (Source: Genome Medicine)
Source: Genome Medicine - September 15, 2022 Category: Genetics & Stem Cells Source Type: research
Leveraging genomic diversity for discovery in an electronic health record linked biobank: the UCLA ATLAS Community Health Initiative
ConclusionsOverall, our results explore the interplay between SIRE and GIA within a disease context and underscore the utility of studying the genomes of diverse individuals through biobank-scale genotyping linked with EHR-based phenotyping. (Source: Genome Medicine)
Source: Genome Medicine - September 9, 2022 Category: Genetics & Stem Cells Source Type: research
Single-cell transcriptomics reveals common epithelial response patterns in human acute kidney injury
ConclusionsThe study provides an extensive resource of the cell type-specific transcriptomic responses associated with critical illness-associated AKI in humans, highlighting recurrent disease-associated signatures and inter-individual heterogeneity. Personalized molecular disease assessment in human AKI may foster the development of tailored therapies. (Source: Genome Medicine)
Source: Genome Medicine - September 9, 2022 Category: Genetics & Stem Cells Source Type: research
Accumulation of copy number alterations and clinical progression across advanced prostate cancer
ConclusionsCopy number alteration in advanced prostate cancer associates with increased risk of metastases at diagnosis. Accumulation of a limited number of copy number alterations associates with most of the increased risk of disease progression and death. The increased likelihood of involvement of specific segments in high copy number alteration burden cancers may suggest an order underlying the accumulation of copy number changes.Trial registrationClinicalTrials.govNCT00268476, registered on December 22, 2005. EudraCT 2004-000193-31, registered on October 4, 2004. (Source: Genome Medicine)
Source: Genome Medicine - September 5, 2022 Category: Genetics & Stem Cells Source Type: research
Clinical trial design in the era of precision medicine
AbstractRecent rapid biotechnological breakthroughs have led to the identification of complex and unique molecular features that drive malignancies. Precision medicine has exploited next-generation sequencing and matched targeted therapy/immunotherapy deployment to successfully transform the outlook for several fatal cancers. Tumor and liquid biopsy genomic profiling and transcriptomic, immunomic, and proteomic interrogation can now all be leveraged to optimize therapy. Multiple new trial designs, including basket and umbrella trials, master platform trials, and N-of-1 patient-centric studies, are beginning to supplant sta...
Source: Genome Medicine - August 31, 2022 Category: Genetics & Stem Cells Source Type: research
Genome-wide interrogation of structural variation reveals novel African-specific prostate cancer oncogenic drivers
ConclusionsIn this first African-inclusive SV study for high-risk PCa, we demonstrate the power of SV interrogation for the identification of novel subtypes, oncogenic drivers and therapeutic targets. Identifying a novel spectrum of SVs in tumours derived from African patients provides a mechanism that may contribute, at least in part, to the observed ethnic disparity in advanced PCa presentation in men of African ancestry. (Source: Genome Medicine)
Source: Genome Medicine - August 31, 2022 Category: Genetics & Stem Cells Source Type: research
A genetic model for central chondrosarcoma evolution correlates with patient outcome
ConclusionsTumours withIDH1 orIDH2 mutations or those that areIDHwt have significantly different genetic pathways and outcomes in relation toTERT mutation. Diagnostic testing forIDH1,IDH2, andTERT mutations could therefore help to guide clinical monitoring and prognostication. (Source: Genome Medicine)
Source: Genome Medicine - August 30, 2022 Category: Genetics & Stem Cells Source Type: research
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
