Identifying chemogenetic interactions from CRISPR screens with drugZ
ConclusionsDrugZ is an open-source Python software for the analysis of genome-scale drug modifier screens. The software accurately identifies genetic perturbations that enhance or suppress drug activity. Interestingly, analysis of new and previously published data reveals tumor suppressor genes are drug-agnostic resistance genes in drug modifier screens. The software is available atgithub.com/hart-lab/drugz. (Source: Genome Medicine)
Source: Genome Medicine - August 22, 2019 Category: Genetics & Stem Cells Source Type: research

A validated single-cell-based strategy to identify diagnostic and therapeutic targets in complex diseases
ConclusionsOverall, our results support that our strategy has the potential to help prioritize diagnostic and therapeutic targets in human disease. (Source: Genome Medicine)
Source: Genome Medicine - July 30, 2019 Category: Genetics & Stem Cells Source Type: research

Correction to: Molecular and pharmacological modulators of the tumor immune contexture revealed by deconvolution of RNA-seq data
It was highlighted that the original article [1] contained a typesetting mistake in the name of Noel Filipe da Cunha Carvalho de Miranda. This was incorrectly captured as Noel Filipe da Cunha Carvahlo de Miranda. It was also highlighted that in Fig.  3C the left panels Y-axis were cropped and in Fig. 5C, CD8 bar was cropped. This Correction article shows the correct Figs. 3 and 5. The original article has been updated. (Source: Genome Medicine)
Source: Genome Medicine - July 29, 2019 Category: Genetics & Stem Cells Source Type: research

Advancing cancer immunotherapy: a vision for the field
(Source: Genome Medicine)
Source: Genome Medicine - July 29, 2019 Category: Genetics & Stem Cells Source Type: research

Hidden Markov models lead to higher resolution maps of mutation signature activity in cancer
AbstractKnowing the activity of the mutational processes shaping a cancer genome may provide insight into tumorigenesis and personalized therapy. It is thus important to characterize the signatures of active mutational processes in patients from their patterns of single base substitutions. However, mutational processes do not act uniformly on the genome, leading to statistical dependencies among neighboring mutations. To account for such dependencies, we develop the first sequence-dependent model, SigMa, for mutation signatures. We apply SigMa to characterize genomic and other factors that influence the activity of mutatio...
Source: Genome Medicine - July 26, 2019 Category: Genetics & Stem Cells Source Type: research

A clinical survey of mosaic single nucleotide variants in disease-causing genes detected by exome sequencing
ConclusionsIn sum, an estimated 1.5% of all molecular diagnoses made in this cohort could be attributed to a mosaic variant detected in the proband, while parental mosaicism was identified in 0.3% of families analyzed. As ES design favors breadth over depth of coverage, this estimate of the prevalence of mosaic variants likely represents an underestimate of the total number of clinically relevant mosaic variants in our cohort. (Source: Genome Medicine)
Source: Genome Medicine - July 26, 2019 Category: Genetics & Stem Cells Source Type: research

Implementation  of a genomic medicine multi-disciplinary team approach for rare disease in the clinical setting: a prospective exome sequencing case series
ConclusionsThis consecutive case series describes the results and experience of a multidisciplinary team format that was found to promote engagement across specialties and facilitate return of results to the responsible clinicians. (Source: Genome Medicine)
Source: Genome Medicine - July 25, 2019 Category: Genetics & Stem Cells Source Type: research

Deciphering drug resistance in Mycobacterium tuberculosis using whole-genome sequencing: progress, promise, and challenges
AbstractTuberculosis (TB) is a global infectious threat that is intensified by an increasing incidence of highly drug-resistant disease. Whole-genome sequencing (WGS) studies ofMycobacterium tuberculosis, the causative agent of TB, have greatly increased our understanding of this pathogen. Since the firstM. tuberculosis genome was published in 1998, WGS has provided a more complete account of the genomic features that cause resistance in populations ofM. tuberculosis, has helped to fill gaps in our knowledge of how both classical and new antitubercular drugs work, and has identified specific mutations that allowM. tubercul...
Source: Genome Medicine - July 25, 2019 Category: Genetics & Stem Cells Source Type: research

Identification of intermediate-sized deletions and inference of their impact on gene expression in a human population
ConclusionsThis paper reports an accurate deletion calling method for genotype imputation at the whole genome level and shows the importance of intermediate-sized deletions in the human population. (Source: Genome Medicine)
Source: Genome Medicine - July 24, 2019 Category: Genetics & Stem Cells Source Type: research

The good, the bad, and the ugly: hyperprogression in cancer patients following immune checkpoint therapy
Editorial summaryImmune checkpoint blockade therapy can elicit robust and durable responses in a variety of cancer types. While many patients do not respond, recent reports highlight a distinct group of patients whose tumors undergo rapid growth, leading to progressive disease and poor outcome. In this perspective, we synthesize and summarize some important issues surrounding hyperprogression, defining characteristics, prognostic implications, and controversies. (Source: Genome Medicine)
Source: Genome Medicine - July 24, 2019 Category: Genetics & Stem Cells Source Type: research

Evolving neoantigen profiles in colorectal cancers with DNA repair defects
ConclusionsThese results indicate that CRCs carrying alterations in DNA repair pathways display dynamic neoantigen patterns that fluctuate over time. We define CRC subsets characterized by slow and fast evolvability and link this phenotype to downregulation of antigen-presenting cellular mechanisms. Longitudinal monitoring of the neoantigen landscape could be relevant in the context of precision medicine. (Source: Genome Medicine)
Source: Genome Medicine - June 28, 2019 Category: Genetics & Stem Cells Source Type: research

Integrating informatics tools and portable sequencing technology for rapid detection of resistance to anti-tuberculous drugs
ConclusionsThe new version ofTBProfiler can rapidly and accurately predict anti-TB drug resistance profiles across large numbers of samples with WGS data. The computing architecture allows for the ability to modify the core bioinformatic pipelines and outputs, including the analysis of WGS data sourced from portable technologies.TBProfiler has the potential to be integrated into the point of care and WGS diagnostic environments, including in resource-poor settings. (Source: Genome Medicine)
Source: Genome Medicine - June 24, 2019 Category: Genetics & Stem Cells Source Type: research

Radiation therapy and anti-tumor immunity: exposing immunogenic mutations to the immune system
AbstractThe expression of antigens that are recognized by self-reactive T cells is essential for immune-mediated tumor rejection by immune checkpoint blockade (ICB) therapy. Growing evidence suggests that mutation-associated neoantigens drive ICB responses in tumors with high mutational burden. In most patients, only a few of the mutations in the cancer exome that are predicted to be immunogenic are recognized by T cells. One factor that limits this recognition is the level of expression of the mutated gene product in cancer cells. Substantial preclinical data show that radiation can convert the irradiated tumor into a sit...
Source: Genome Medicine - June 20, 2019 Category: Genetics & Stem Cells Source Type: research

Mechanisms of immune-related adverse events associated with immune checkpoint blockade: using germline genetics to develop a personalized approach
Editorial summaryPersonalized care of cancer patients undergoing treatment with immune checkpoint inhibitors will require approaches that can predict their susceptibility to immune-related adverse events. Understanding the role of germline genetic factors in determining individual responses to immunotherapy will deepen our understanding of immune toxicity and, importantly, it may lead to tools for identifying patients who are at risk. (Source: Genome Medicine)
Source: Genome Medicine - June 20, 2019 Category: Genetics & Stem Cells Source Type: research

Exome sequencing in routine diagnostics: a generic test for 254 patients with primary immunodeficiencies
ConclusionExome sequencing as a first-tier test for PIDs granted a diagnosis for 28% of patients. Importantly, molecularly defined diagnoses indicated altered therapeutic options in 34% of cases. In addition, exome sequencing harbors advantages over gene panels as a truly generic test for all genetic diseases, including in silico extension of existing gene lists and re-analysis of existing data. (Source: Genome Medicine)
Source: Genome Medicine - June 17, 2019 Category: Genetics & Stem Cells Source Type: research

Prognostic value of B cells in cutaneous melanoma
ConclusionsThese findings suggest an important prognostic and predictive role for B cell characteristics in SKCM. This has implications for melanoma immunobiology and potential development of immunogenomics features to predict survival and response to immunotherapy. (Source: Genome Medicine)
Source: Genome Medicine - May 28, 2019 Category: Genetics & Stem Cells Source Type: research

Associating somatic mutations to clinical outcomes: a pan-cancer study of survival time
AbstractWe developed subclone multiplicity allocation and somatic heterogeneity (SMASH), a new statistical method for intra-tumor heterogeneity (ITH) inference. SMASH is tailored to the purpose of large-scale association studies with one tumor sample per patient. In a pan-cancer study of 14 cancer types, we studied the associations between survival time and ITH quantified by SMASH, together with other features of somatic mutations. Our results show that ITH is associated with survival time in several cancer types and its effect can be modified by other covariates, such as mutation burden. SMASH is available athttps://githu...
Source: Genome Medicine - May 28, 2019 Category: Genetics & Stem Cells Source Type: research

Somatic mutation and clonal expansions in human tissues
Editorial summaryRecent sequencing studies on healthy skin and esophagus have found that, as we age, these tissues become colonized by mutant clones of cells carrying driver mutations in traditional cancer genes. This comment summarizes these findings and discusses their possible implications for our understanding of cancer, ageing, and other diseases. (Source: Genome Medicine)
Source: Genome Medicine - May 28, 2019 Category: Genetics & Stem Cells Source Type: research

Clinical utility of custom-designed NGS panel testing in pediatric tumors
ConclusionsUse of somatic NGS panel testing resulted in a significant impact on clinical care, including diagnosis, prognosis, and treatment planning in 78.7% of pediatric patients tested in our institution. Somatic NGS tumor testing should be implemented as part of the routine diagnostic workup of newly diagnosed and relapsed pediatric cancer patients. (Source: Genome Medicine)
Source: Genome Medicine - May 28, 2019 Category: Genetics & Stem Cells Source Type: research

Dissecting lung development and fibrosis at single-cell resolution
Editorial summarySingle-cell transcriptome profiling has enabled high-resolution analysis of cellular populations in tissues during development, health, and disease. Recent studies make innovative use of single-cell RNA sequencing (scRNAseq) to investigate mechanisms that allow immune cells to interact with tissue components in the lung during development and fibrotic lung disease. (Source: Genome Medicine)
Source: Genome Medicine - May 24, 2019 Category: Genetics & Stem Cells Source Type: research

Molecular and pharmacological modulators of the tumor immune contexture revealed by deconvolution of RNA-seq data
AbstractWe introduce quanTIseq, a method to quantify the fractions of ten immune cell types from bulk RNA-sequencing data. quanTIseq was extensively validated in blood and tumor samples using simulated, flow cytometry, and immunohistochemistry data.quanTIseq analysis of 8000 tumor samples revealed that cytotoxic T cell infiltration is more strongly associated with the activation of the CXCR3/CXCL9 axis than with mutational load and that deconvolution-based cell scores have prognostic value in several solid cancers. Finally, we used quanTIseq to show how kinase inhibitors modulate the immune contexture and to reveal immune-...
Source: Genome Medicine - May 24, 2019 Category: Genetics & Stem Cells Source Type: research

Points-to-consider on the return of results in epigenetic research
AbstractAs epigenetic studies become more common and lead to new insights into health and disease, the return of individual epigenetic results to research participants, in particular in large-scale epigenomic studies, will be of growing importance. Members of the International Human Epigenome Consortium (IHEC) Bioethics Workgroup considered the potential ethical, legal, and social issues (ELSI) involved in returning epigenetic research results and incidental findings in order to produce a set of ‘Points-to-consider’ (P-t-C) for the epigenetics research community. These P-t-C draw on existing guidance on the ret...
Source: Genome Medicine - May 23, 2019 Category: Genetics & Stem Cells Source Type: research

Copy number variant and runs of homozygosity detection by microarrays enabled more precise molecular diagnoses in 11,020 clinical exome cases
ConclusionsOur clinical genomics study demonstrates that detection of PCNV/UPD through the QC array or CMA increases ES diagnostic rate, provides more precise molecular diagnosis for dominant as well as recessive traits, and enables more complete genetic diagnoses in patients with dual or multiple molecular diagnoses. Concurrent ES and CMA using an array with exonic coverage for disease genes enables most effective detection of both CNVs and SNVs and therefore is recommended especially in time-sensitive clinical situations. (Source: Genome Medicine)
Source: Genome Medicine - May 17, 2019 Category: Genetics & Stem Cells Source Type: research

Multi-omics discovery of exome-derived neoantigens in hepatocellular carcinoma
ConclusionsThis study suggests that exome-derived mutated HLA ligands appear to be rarely presented in HCCs,inter alia resulting from a low mutational burden as compared to other malignancies such as malignant  melanoma. Our results therefore demand widening the target scope for personalized immunotherapy beyond this limited range of mutated neoepitopes, particularly for malignancies with similar or lower mutational burden. (Source: Genome Medicine)
Source: Genome Medicine - April 30, 2019 Category: Genetics & Stem Cells Source Type: research

A modular transcriptome map of mature B cell lymphomas
ConclusionsThe transcriptome map provides a tool that aggregates, refines and visualizes the data collected in the MMML study and interprets them in the light of previous knowledge to provide orientation and support in current and future studies on lymphomas and on other cancer entities. (Source: Genome Medicine)
Source: Genome Medicine - April 30, 2019 Category: Genetics & Stem Cells Source Type: research

Evidence from genome wide association studies implicates reduced control of Epstein-Barr virus infection in multiple sclerosis susceptibility
AbstractBackgroundGenome wide association studies have identified>  200 susceptibility loci accounting for much of the heritability of multiple sclerosis (MS). Epstein-Barr virus (EBV), a memory B cell tropic virus, has been identified as necessary but not sufficient for development of MS. The molecular and immunological basis for this has not been established. I nfected B cell proliferation is driven by signalling through the EBV produced cell surface protein LMP1, a homologue of the MS risk gene CD40.MethodsWe have investigated transcriptomes of B cells and EBV-infected B cells at Latency III (LCLs) and identif...
Source: Genome Medicine - April 30, 2019 Category: Genetics & Stem Cells Source Type: research

Discovery and characterization of actionable tumor antigens
Editorial summaryThe nature of the tumor antigens that are detectable by T cells remains unclear. In melanoma, T cells were shown to react against major histocompatibility complex (MHC)-associated peptides (MAPs) that are derived from exonic mutations. A recent multi-omic study of hepatocellular carcinomas suggests, however, that mutated exonic MAPs were exceedingly rare, bringing the accuracy of the current methods for antigen identification into question and demonstrating the importance of broadening tumor-antigen discovery efforts. (Source: Genome Medicine)
Source: Genome Medicine - April 30, 2019 Category: Genetics & Stem Cells Source Type: research

TCF21 and AP-1 interact through epigenetic modifications to regulate coronary artery disease gene expression
ConclusionsThese data show that the known chromatin remodeling and pioneer functions of AP-1 are a pervasive aspect of epigenetic control of transcription, and thus, the risk in coronary disease-associated loci, and that interaction of AP-1 with TCF21 to control epigenetic features, contributes to the genetic risk in loci where they co-localize. (Source: Genome Medicine)
Source: Genome Medicine - April 23, 2019 Category: Genetics & Stem Cells Source Type: research

Interchromosomal template-switching as a novel molecular mechanism for imprinting perturbations associated with Temple syndrome
ConclusionsThese data provide experimental evidence that, in humans, triplication can lead to segmental UPD and imprinting disease. Importantly, genotype/phenotype analyses further reveal how a post-zygotically generated complex structural variant, resulting from a replication-based mutational mechanism, contributes to expanding the clinical phenotype of known genetic syndromes. Mechanistically, such events can distort transmission genetics resulting in homozygosity at a locus for which only one parent is a carrier as well as cause imprinting diseases. (Source: Genome Medicine)
Source: Genome Medicine - April 23, 2019 Category: Genetics & Stem Cells Source Type: research

Molecular basis for phenotypic similarity of genetic disorders
This study highlights how structural similarity among genes contributes to shared phenotypes, and shows how this relationship can contribute to our understanding of the genetic basis of complex disorders. (Source: Genome Medicine)
Source: Genome Medicine - April 23, 2019 Category: Genetics & Stem Cells Source Type: research

Designing circulating tumor DNA-based interventional clinical trials in oncology
Editorial summaryCirculating tumor (ct) DNA is a powerful tool that can be used to track cancer beyond a single snapshot in space and time. It has potential applications in detecting minimal residual disease and predicting relapse, in selecting patients for tailored treatments, and in revealing mechanisms of response or resistance. Here, we discuss the incorporation of ctDNA into clinical trials. (Source: Genome Medicine)
Source: Genome Medicine - April 19, 2019 Category: Genetics & Stem Cells Source Type: research

CRISPR-SONIC: targeted somatic oncogene knock-in enables rapid in vivo cancer modeling
AbstractCRISPR/Cas9 has revolutionized cancer mouse models. Although loss-of-function genetics by CRISPR/Cas9 is well-established, generating gain-of-function alleles in somatic cancer models is still challenging because of the low efficiency of gene knock-in. Here we developed CRISPR-based Somatic Oncogene kNock-In for Cancer Modeling (CRISPR-SONIC), a method for rapid in vivo cancer modeling using homology-independent repair to integrate oncogenes at a targeted genomic locus. Using a dual guide RNA strategy, we integrated a plasmid donor in the 3 ′-UTR of mouse β-actin, allowing co-expression of reporter genes...
Source: Genome Medicine - April 16, 2019 Category: Genetics & Stem Cells Source Type: research

Translating insights into tumor evolution to clinical practice: promises and challenges
AbstractAccelerating technological advances have allowed the widespread genomic profiling of tumors. As yet, however, the vast catalogues of mutations that have been identified have made only a modest impact on clinical medicine. Massively parallel sequencing has informed our understanding of the genetic evolution and heterogeneity of cancers, allowing us to place these mutational catalogues into a meaningful context. Here, we review the methods used to measure tumor evolution and heterogeneity, and the potential and challenges for translating the insights gained to achieve clinical impact for cancer therapy, monitoring, e...
Source: Genome Medicine - March 29, 2019 Category: Genetics & Stem Cells Source Type: research

Developing a network view of type 2 diabetes risk pathways through integration of genetic, genomic and functional data
ConclusionsThese analyses reveal a pattern of non-random functional connectivity between candidate causal genes at T2D GWAS loci and highlight the products of genes includingYWHAG,SMAD4 orCDK2 as potential contributors to T2D-relevant islet dysfunction. The approach we describe can be applied to other complex genetic and genomic datasets, facilitating integration of diverse data types into disease-associated networks. (Source: Genome Medicine)
Source: Genome Medicine - March 26, 2019 Category: Genetics & Stem Cells Source Type: research

Encircling the regions of the pharmacogenomic landscape that determine drug response
ConclusionsNetwork biology strategies like module detection are able to digest the outcome of large-scale pharmacogenomic initiatives, thereby contributing to their interpretability and improving the characterization of the drugs screened. (Source: Genome Medicine)
Source: Genome Medicine - March 26, 2019 Category: Genetics & Stem Cells Source Type: research

Loss of BAP1 as a candidate predictive biomarker for immunotherapy of mesothelioma
AbstractAs trials of immune checkpoint inhibitor (ICI) therapies demonstrate responses in only a minority of pleural mesotheliomas (PlMs) and largely exclude patients with the related peritoneal mesothelioma (PeM), clinicians need predictive biomarkers of response and inclusion of PeM patients in future trials. A new study finds that loss of the deubiquitinase BAP1 in PeM correlates with an inflammatory tumor microenvironment, suggesting thatBAP1 status might identify PeM, and possibly PlM, patients who would benefit from ICI therapy. (Source: Genome Medicine)
Source: Genome Medicine - March 26, 2019 Category: Genetics & Stem Cells Source Type: research

Correction to: De novo and inherited TCF20 pathogenic variants are associated with intellectual disability, dysmorphic features, hypotonia, and neurological impairments with similarities to Smith –Magenis syndrome
It was highlighted that the original article [1] contained a typographical error in the Results section. Subject 17 was incorrectly cited as Subject 1. This Correction article shows the revised statement. The original article has been updated. (Source: Genome Medicine)
Source: Genome Medicine - March 25, 2019 Category: Genetics & Stem Cells Source Type: research

Circular RNAs as promising biomarkers in cancer: detection, function, and beyond
Editorial summaryCircular RNAs (circRNAs) are 3 ′–5′ covalently closed RNA rings produced from back-splicing of precursor mRNA in eukaryotes. Recent studies, using both computational and experimental approaches, have allowed advanced characterization of circRNAs, leading the research field into a new era and shedding light on the contributi on of circRNAs to disease. (Source: Genome Medicine)
Source: Genome Medicine - March 20, 2019 Category: Genetics & Stem Cells Source Type: research

Correction to: NSAID use and somatic exomic mutations in Barrett ’s esophagus
It was highlighted that in the original article [1] the Availability of data and materials section was incorrect. (Source: Genome Medicine)
Source: Genome Medicine - March 12, 2019 Category: Genetics & Stem Cells Source Type: research

De novo and inherited TCF20 pathogenic variants are associated with intellectual disability, dysmorphic features, hypotonia, and neurological impairments with similarities to Smith –Magenis syndrome
ConclusionsTCF20 pathogenic variants are associated with a novel syndrome manifesting clinical characteristics similar to those observed in Smith –Magenis syndrome. Together with previously described cases, the clinical entity ofTCF20-associated neurodevelopmental disorders (TAND) emerges from a genotype-driven perspective. (Source: Genome Medicine)
Source: Genome Medicine - February 28, 2019 Category: Genetics & Stem Cells Source Type: research

A decade of Genome Medicine: toward precision medicine
(Source: Genome Medicine)
Source: Genome Medicine - February 28, 2019 Category: Genetics & Stem Cells Source Type: research

Predispositional genome sequencing in healthy adults: design, participant characteristics, and early outcomes of the PeopleSeq Consortium
AbstractBackgroundIncreasing numbers of healthy individuals are undergoing predispositional personal genome sequencing. Here we describe the design and early outcomes of the PeopleSeq Consortium, a multi-cohort collaboration of predispositional genome sequencing projects, which is examining the medical, behavioral, and economic outcomes of returning genomic sequencing information to healthy individuals.MethodsApparently healthy adults who participated in four of the sequencing projects in the Consortium were included. Web-based surveys were administered before and after genomic results disclosure, or in some cases only aft...
Source: Genome Medicine - February 27, 2019 Category: Genetics & Stem Cells Source Type: research

Impact of the gut microbiome on the genome and epigenome of colon epithelial cells: contributions to colorectal cancer development
AbstractIn recent years, the number of studies investigating the impact of the gut microbiome in colorectal cancer (CRC) has risen sharply. As a result, we now know that various microbes (and microbial communities) are found more frequently in the stool and mucosa of individuals with CRC than healthy controls, including in the primary tumors themselves, and even in distant metastases. We also know that these microbes induce tumors in various mouse models, but we know little about how they impact colon epithelial cells (CECs) directly, or about how these interactions might lead to modifications at the genetic and epigenetic...
Source: Genome Medicine - February 25, 2019 Category: Genetics & Stem Cells Source Type: research

Translating genomic medicine to the clinic: challenges and opportunities
Editorial summaryGenomic medicine has considerable potential to provide novel diagnostic and therapeutic solutions for patients who have molecularly complex diseases and who are not responding to existing therapies. To bridge the gap between genomic medicine and clinical practice, integration of various data types, resources, and joint international initiatives will be required. (Source: Genome Medicine)
Source: Genome Medicine - February 22, 2019 Category: Genetics & Stem Cells Source Type: research

BAP1 haploinsufficiency predicts a distinct immunogenic class of malignant peritoneal mesothelioma
ConclusionsOur findings revealBAP1 to be a potential, easily trackable prognostic and predictive biomarker for PeM immunotherapy that refines PeM disease classification.BAP1 stratification may improve drug response rates in ongoing phases I and II clinical trials exploring the use of immune checkpoint blockade therapies in PeM in whichBAP1 status is not considered. This integrated molecular characterization provides a comprehensive foundation for improved management of a subset of PeM patients. (Source: Genome Medicine)
Source: Genome Medicine - February 18, 2019 Category: Genetics & Stem Cells Source Type: research

Ten years of Genome Medicine
(Source: Genome Medicine)
Source: Genome Medicine - February 15, 2019 Category: Genetics & Stem Cells Source Type: research

Prioritizing putative influential genes in cardiovascular disease susceptibility by applying tissue-specific Mendelian randomization
ConclusionsDisease susceptibility can be influenced by differential changes in tissue-specific gene expression and DNA methylation. The approach undertaken in our study can be used to elucidate mechanisms in disease, as well as helping prioritize putative causal genes at associated loci where multiple nearby genes may be co-regulated. Future studies which continue to uncover quantitative trait loci for molecular traits across various tissue and cell types will further improve our capability to understand and prevent disease. (Source: Genome Medicine)
Source: Genome Medicine - January 31, 2019 Category: Genetics & Stem Cells Source Type: research

Quantitative approaches to variant classification increase the yield and precision of genetic testing in Mendelian diseases: the case of hypertrophic cardiomyopathy
ConclusionsWhen found in a patient confirmed to have disease, novel variants in some genes and regions are empirically shown to have a sufficiently high probability of pathogenicity to support a “likely pathogenic” classification, even without additional segregation or functional data. This could increase the yield of high confidence actionable variants, consistent with the framework and recommendations of current guidelines. The techniques outlined offer a consistent and unbiased appro ach to variant interpretation for Mendelian disease genetic testing. We propose adaptations to ACMG/AMP guidelines to incorpor...
Source: Genome Medicine - January 29, 2019 Category: Genetics & Stem Cells Source Type: research

From genome integrity to cancer
(Source: Genome Medicine)
Source: Genome Medicine - January 29, 2019 Category: Genetics & Stem Cells Source Type: research

Single-cell analysis reveals congruence between kidney organoids and human fetal kidney
ConclusionsThis study supports the fidelity of kidney organoids as models of the developing kidney and affirms their potential in disease modelling and drug screening. (Source: Genome Medicine)
Source: Genome Medicine - January 23, 2019 Category: Genetics & Stem Cells Source Type: research