Genomic and transcriptomic analysis of a diffuse pleural mesothelioma patient-derived xenograft library
ConclusionsThese data demonstrate that DPM PDX models closely resemble the genotype and phenotype of parental tumors, and identify pathways altered in DPM for future exploration in preclinical studies. (Source: Genome Medicine)
Source: Genome Medicine - November 15, 2022 Category: Genetics & Stem Cells Source Type: research
Network reconstruction for trans acting genetic loci using multi-omics data and prior information
ConclusionsWe demonstrate that existing biological knowledge can improve the integrative analysis of networks underlyingtrans associations and generate novel hypotheses about regulatory mechanisms. (Source: Genome Medicine)
Source: Genome Medicine - November 7, 2022 Category: Genetics & Stem Cells Source Type: research
Ganciclovir-induced mutations are present in a diverse spectrum of post-transplant malignancies
ConclusionsIn summary, GCV can cause a diverse range of cancers. Its mutagenicity may be potentiated by other therapies, such as mycophenolate, commonly co-prescribed with GCV for post-transplant patients. Further investigation of the optimal use of these drugs could help reduce GCV-associated mutagenesis in post-transplant patients. (Source: Genome Medicine)
Source: Genome Medicine - October 31, 2022 Category: Genetics & Stem Cells Source Type: research
Application of exome sequencing for prenatal diagnosis of fetal structural anomalies: clinical experience and lessons learned from a cohort of 1618 fetuses
ConclusionsThe genotype-driven approach could identify about 81.7% positive cases (11.6% of the total cohort) with the initial limited fetal phenotype information considered. The following two steps of phenotype-driven analysis and data reanalyses helped us find the causative variants in an additional 2.6% of the entire cohort (18.3% of all positive findings). Our extensive phenotype analysis on a large number of molecularly confirmed prenatal cases had greatly enriched our current knowledge on fetal phenotype-genotype correlation, which may guide more focused prenatal ultrasound in the future. This is by far the largest p...
Source: Genome Medicine - October 28, 2022 Category: Genetics & Stem Cells Source Type: research
The lung microbiome, peripheral gene expression, and recurrence-free survival after resection of stage II non-small cell lung cancer
ConclusionsWe identified compelling biomarkers in under-explored data types, the lung microbiome, and peripheral blood gene expression, which may improve risk prediction of recurrence in early-stage NSCLC patients. These findings will require validation in a larger cohort. (Source: Genome Medicine)
Source: Genome Medicine - October 27, 2022 Category: Genetics & Stem Cells Source Type: research
The multiple de novo copy number variant (MdnCNV) phenomenon presents with peri-zygotic DNA mutational signatures and multilocus pathogenic variation
ConclusionsCharacteristic features ofdnCNVs reported here are consistent with a microhomology-mediated break-induced replication (MMBIR)-driven mechanism during the peri-zygotic period. Maternal genetic variants in DNA repair genes potentially contribute to peri-zygotic genomic instability. Variable phenotypic features were observed across a cohort of three MdnCNV probands, and computational quantitative phenotyping revealed that two out of three had evidence for the contribution of more than one genetic locus to the proband ’s phenotype supporting the hypothesis ofde novo multilocus pathogenic variation (MPV) in those f...
Source: Genome Medicine - October 27, 2022 Category: Genetics & Stem Cells Source Type: research
Computational quantification and characterization of independently evolving cellular subpopulations within tumors is critical to inhibit anti-cancer therapy resistance
ConclusionsWe show that a barcode-guided targeted drug cocktail significantly enhances tumor response to RT and prevents regrowth of once-resistant tumors. The strategy presented herein shows promise in preventing cancer treatment resistance, with significant applicability in clinical use. (Source: Genome Medicine)
Source: Genome Medicine - October 20, 2022 Category: Genetics & Stem Cells Source Type: research
The WID-CIN test identifies women with, and at risk of, cervical intraepithelial neoplasia grade 3 and invasive cervical cancer
ConclusionsThe WID-CIN test identifies the vast majority of hrHPV-positive women with current CIN3+ lesions. In the absence of cytologic abnormalities, a positive WID-CIN test result is likely to indicate a significantly increased risk of developing CIN3+ in the near future. (Source: Genome Medicine)
Source: Genome Medicine - October 19, 2022 Category: Genetics & Stem Cells Source Type: research
CTpathway: a CrossTalk-based pathway enrichment analysis method for cancer research
ConclusionsCollectively, CTpathway is a fast, accurate, and stable pathway enrichment analysis method for cancer research that can be used to identify cancer risk pathways. The CTpathway interactive web server can be accessed herehttp://www.jianglab.cn/CTpathway/. The stand-alone program can be accessed herehttps://github.com/Bioccjw/CTpathway. (Source: Genome Medicine)
Source: Genome Medicine - October 13, 2022 Category: Genetics & Stem Cells Source Type: research
Mendelian gene identification through mouse embryo viability screening
ConclusionsInformation on the developmental period at which embryonic lethality occurs in the knockout mouse may be used for novel disease gene discovery that helps to prioritise variants in unsolved rare disease cases. (Source: Genome Medicine)
Source: Genome Medicine - October 13, 2022 Category: Genetics & Stem Cells Source Type: research
Correction: Elucidating the diversity of malignant mesenchymal states in glioblastoma by integrative analysis
(Source: Genome Medicine)
Source: Genome Medicine - October 12, 2022 Category: Genetics & Stem Cells Source Type: research
MetaRNN: differentiating rare pathogenic and rare benign missense SNVs and InDels using deep learning
AbstractMultiple computational approaches have been developed to improve our understanding of genetic variants. However, their ability to identify rare pathogenic variants from rare benign ones is still lacking. Using context annotations and deep learning methods, we present pathogenicity prediction models, MetaRNN and MetaRNN-indel, to help identify and prioritize rare nonsynonymous single nucleotide variants (nsSNVs) and non-frameshift insertion/deletions (nfINDELs). We use independent test sets to demonstrate that these new models outperform state-of-the-art competitors and achieve a more interpretable score distributio...
Source: Genome Medicine - October 8, 2022 Category: Genetics & Stem Cells Source Type: research
Patient and provider perspectives on polygenic risk scores: implications for clinical reporting and utilization
ConclusionsPCPs saw PRS information as a natural extension of their current practice. The most pressing gap for PRS implementation is evidence for clinical utility. Careful clinical report design can help ensure that benefits are realized and harms are minimized. (Source: Genome Medicine)
Source: Genome Medicine - October 7, 2022 Category: Genetics & Stem Cells Source Type: research
Sequencing individual genomes with recurrent genomic disorder deletions: an approach to characterize genes for autosomal recessive rare disease traits
ConclusionsOur results demonstrate that genomic sequencing of personal genomes with NAHR deletions could dramatically improve allele and gene discovery and enhance clinical molecular diagnosis. Moreover, results suggest NAHR events could potentially enable human haploid genetic screens as an approach to experimental inquiry into disease biology. (Source: Genome Medicine)
Source: Genome Medicine - September 30, 2022 Category: Genetics & Stem Cells Source Type: research
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
