Multiple PIK3CA mutation clonality correlates with outcomes in taselisib + fulvestrant-treated ER+/HER2 –, PIK3CA-mutated breast cancers
ConclusionsOur study establishes clonal multiplePIK3CAmut as an important molecular determinant of response to p110 α inhibition and provides rationale for further clinical investigation of p110α inhibitors alone or with rationally-selected therapies in breast cancer and potentially other solid tumor types. (Source: Genome Medicine)
Source: Genome Medicine - April 26, 2023 Category: Genetics & Stem Cells Source Type: research
ACT-Discover: identifying karyotype heterogeneity in pancreatic cancer evolution using ctDNA
ConclusionsThis work demonstrates the power of haplotype phasing to study genomic variation in cfDNA samples and reveals undiscovered intra-tumour heterogeneity with important scientific and clinical implications. Implementation of ACT-Discover could lead to important insights from existing cohorts or underpin future prospective studies seeking to characterise the landscape of tumour evolution through liquid biopsy. (Source: Genome Medicine)
Source: Genome Medicine - April 20, 2023 Category: Genetics & Stem Cells Source Type: research
Diagnostic yield of genetic screening in a diverse, community-ascertained cohort
ConclusionsPopulation screening can identify additional individuals that could benefit from prevention, but challenges in recruitment and sample collection will reduce actual enrollment and yield. These challenges should not be overlooked in intervention planning or in cost and benefit analysis. (Source: Genome Medicine)
Source: Genome Medicine - April 18, 2023 Category: Genetics & Stem Cells Source Type: research
Molecular characteristics of breast tumors in patients screened for germline predisposition from a population-based observational study
ConclusionsCharacterization of molecular tumor features in patients clinically screened and not screened for PGVs represents a relevant read-out of guideline criteria. The general lack of molecular differences between screened/non-screened patients after stratification by relevant breast cancer subsets questions the ability to improve the identification of screening candidates based on currently used patient and tumor characteristics, pointing us towards universal screening. Nevertheless, while that is not attained, molecular differences identified between PGV carriers/non-carriers suggest the possibility of further refini...
Source: Genome Medicine - April 14, 2023 Category: Genetics & Stem Cells Source Type: research
Stalled oligodendrocyte differentiation in IDH-mutant gliomas
ConclusionsOur studies show that despite differences in clinical manifestation and genomic alterations, all IDH-mutant gliomas resemble early stages of oligodendrocyte lineage and are stalled in oligodendrocyte differentiation due to blocked myelination program. These findings provide a framework to accommodate biological features and therapy development for IDH-mutant gliomas. (Source: Genome Medicine)
Source: Genome Medicine - April 13, 2023 Category: Genetics & Stem Cells Source Type: research
Correction: FOXC1-mediated LINC00301 facilitates tumor progression and triggers an immune-suppressing microenvironment in non-small cell lung cancer by regulating the HIF1α pathway
(Source: Genome Medicine)
Source: Genome Medicine - April 12, 2023 Category: Genetics & Stem Cells Source Type: research
Rare predicted loss-of-function variants of type I IFN immunity genes are associated with life-threatening COVID-19
ConclusionsRare variants of TLR3- and TLR7-dependent type I IFN immunity genes can underlie life-threatening COVID-19, particularly with recessive inheritance, in patients under 60 years old. (Source: Genome Medicine)
Source: Genome Medicine - April 5, 2023 Category: Genetics & Stem Cells Source Type: research
A novel transcriptional signature identifies T-cell infiltration in high-risk paediatric cancer
ConclusionsOur data provides new insights into the variable immune-suppressive mechanisms dampening responses in paediatric solid cancers. Effective immune-based interventions in high-risk paediatric cancer will require individualised analysis of the TIME. (Source: Genome Medicine)
Source: Genome Medicine - April 3, 2023 Category: Genetics & Stem Cells Source Type: research
X chromosome dosage and the genetic impact across human tissues
ConclusionWe highlight a tissue-specific and complex effect of X chromosome number on the transcriptome and methylome, elucidating both shared and non-shared gene-regulatory mechanism between SCAs. (Source: Genome Medicine)
Source: Genome Medicine - March 28, 2023 Category: Genetics & Stem Cells Source Type: research
spSeudoMap: cell type mapping of spatial transcriptomics using unmatched single-cell RNA-seq data
AbstractSince many single-cell RNA-seq (scRNA-seq) data are obtained after cell sorting, such as when investigating immune cells, tracking cellular landscape by integrating single-cell data with spatial transcriptomic data is limited due to cell type and cell composition mismatch between the two datasets. We developed a method, spSeudoMap, which utilizes sorted scRNA-seq data to create virtual cell mixtures that closely mimic the gene expression of spatial data and trains a domain adaptation model for predicting spatial cell compositions. The method was applied in brain and breast cancer tissues and accurately predicted th...
Source: Genome Medicine - March 17, 2023 Category: Genetics & Stem Cells Source Type: research
Automated prioritization of sick newborns for whole genome sequencing using clinical natural language processing and machine learning
ConclusionsOur results indicate that an automated pipeline for selecting acutely ill infants in neonatal intensive care units (NICU) for WGS can meet or exceed diagnostic yields obtained through current selection procedures, which require time-consuming manual review of clinical notes and histories by specialized personnel. (Source: Genome Medicine)
Source: Genome Medicine - March 16, 2023 Category: Genetics & Stem Cells Source Type: research
Combinatorial batching of DNA for ultralow-cost detection of pathogenic variants
ConclusionsOur ultracheap genetic diagnostic method, which uses existing sequencing hardware and standard newborn blood spots, should readily open up opportunities for population-wide risk stratification using genetic screening across many fields of clinical genetics and genomics. (Source: Genome Medicine)
Source: Genome Medicine - March 14, 2023 Category: Genetics & Stem Cells Source Type: research
Pharmacogenomic profiling reveals molecular features of chemotherapy resistance in IDH wild-type primary glioblastoma
ConclusionsWe identified molecular characteristics associated to TMZ sensitivity, and illustrate the potential clinical value of a ML model trained from pharmacogenomic profiling of patient-derived GSC against IDH-wt GBMs. (Source: Genome Medicine)
Source: Genome Medicine - March 13, 2023 Category: Genetics & Stem Cells Source Type: research
Influence network model uncovers relations between biological processes and mutational signatures
ConclusionsGeneSigNet provides a new and powerful method to reveal the relation between mutational signatures and gene expression. TheGeneSigNet method was implemented in python, and installable package, source codes and the data sets used for and generated during this study are available at the Github sitehttps://github.com/ncbi/GeneSigNet. (Source: Genome Medicine)
Source: Genome Medicine - March 6, 2023 Category: Genetics & Stem Cells Source Type: research
Tumor microenvironment remodeling after neoadjuvant immunotherapy in non-small cell lung cancer revealed by single-cell RNA sequencing
ConclusionsNeoadjuvant PD-1 blockade combined with chemotherapy led to distinct NSCLC tumor microenvironment transcriptomes that correlated with therapy response. Although limited by a small patient sample size subjected to combination therapy, this study provides novel biomarkers to predict therapy response and suggests potential strategies to overcome immunotherapy resistance. (Source: Genome Medicine)
Source: Genome Medicine - March 3, 2023 Category: Genetics & Stem Cells Source Type: research
