Fecal microbiota transplantation in gastrointestinal disorders: time for precision medicine
AbstractFecal microbiota transplantation (FMT) has demonstrated efficacy in treating inflammatory bowel diseases and irritable bowel syndrome in an increasing number of randomized controlled trials. Recently published data gives striking insights into the factors associated with FMT success paving the road for the use of precision medicine in gastrointestinal disorders. (Source: Genome Medicine)
Source: Genome Medicine - June 30, 2020 Category: Genetics & Stem Cells Source Type: research

Multiple approaches for massively parallel sequencing of SARS-CoV-2 genomes directly from clinical samples
ConclusionsThis is, to the best of our knowledge, the first work systematically investigating inter- and intra-individual variations of SARS-CoV-2 using amplicon- and capture-based whole-genome sequencing, as well as the first comparative study among multiple approaches. Our work offers practical solutions for genome sequencing and analyses of SARS-CoV-2 and other emerging viruses. (Source: Genome Medicine)
Source: Genome Medicine - June 30, 2020 Category: Genetics & Stem Cells Source Type: research

A comparison of epigenetic mitotic-like clocks for cancer risk prediction
ConclusionsThese results have profound implications for our understanding of epigenetic clocks and for developing cancer risk prediction or early detection assays. We propose that measurement of DNAm at the 163 epiTOC2 CpGs in adult pre-neoplastic lesions, and potentially in serum cell-free DNA, could provide the basis for building feasible pre-diagnostic or cancer risk assays. epiTOC2 is freely available fromhttps://doi.org/10.5281/zenodo.2632938 (Source: Genome Medicine)
Source: Genome Medicine - June 24, 2020 Category: Genetics & Stem Cells Source Type: research

Discovery of CD80 and CD86 as recent activation markers on regulatory T cells by protein-RNA single-cell analysis
ConclusionsThe transcriptomic and proteomic hybrid technology described in this study  provides a cost-effective solution to dissect the heterogeneity of immune cell populations at extremely high resolution. Unexpectedly, CD80 and CD86, normally expressed on antigen-presenting cells, were detected on a subset of activated Tregs, indicating a role for these co-stimulatory molecules in regulating the dynamics of CD4+ T cell responses. (Source: Genome Medicine)
Source: Genome Medicine - June 24, 2020 Category: Genetics & Stem Cells Source Type: research

cfNOMe — A single assay for comprehensive epigenetic analyses of cell-free DNA
We presentcfNOMe, a two-in-one method of measuring cfDNA cytosine methylation and nucleosome occupancy in a single assay using non-disruptive enzymatic cytosine conversion and a custom bioinformatic pipeline. We show that enzymatic cytosine conversion better preserves cfDNA fragmentation information than does bisulfite conversion. Whereas previously separate experiments were required to study either epigenetic marking,cfNOMe delivers reliable results for both, enabling more comprehensive and inexpensive epigenetic cfDNA profiling.cfNOMe has the potential to advance biomarker discovery and diagnostic usage in diseases with ...
Source: Genome Medicine - June 24, 2020 Category: Genetics & Stem Cells Source Type: research

Whole-genome sequence association analysis of blood proteins in a longitudinal wellness cohort
AbstractBackgroundThe human plasma proteome is important for many biological processes and targets for diagnostics and therapy. It is therefore of great interest to understand the interplay of genetic and environmental factors to determine the specific protein levels in individuals and to gain a deeper insight of the importance of genetic architecture related to the individual variability of plasma levels of proteins during adult life.MethodsWe have combined whole-genome sequencing, multiplex plasma protein profiling, and extensive clinical phenotyping in a longitudinal 2-year wellness study of 101 healthy individuals with...
Source: Genome Medicine - June 23, 2020 Category: Genetics & Stem Cells Source Type: research

Network-based approaches elucidate differences within APOBEC and clock-like signatures in breast cancer
ConclusionsThis work investigated, for the first time, a network-level association of mutational signatures and dysregulated pathways. The identified pathways and subnetworks provide novel insights into mutagenic processes that the cancer genomes might have undergone and important clues for developing personalized drug therapies. (Source: Genome Medicine)
Source: Genome Medicine - May 29, 2020 Category: Genetics & Stem Cells Source Type: research

Strain-resolved microbiome sequencing reveals mobile elements that drive bacterial competition on a clinical timescale
ConclusionsWe find read cloud assembly to be useful in identifying key structural genomic strain variants within a metagenomic sample. These strains have fluctuating relative abundance over relatively short time periods in human microbiomes. We also find specific structural genomic variations that are associated with increased antibiotic resistance over the course of clinical treatment. (Source: Genome Medicine)
Source: Genome Medicine - May 29, 2020 Category: Genetics & Stem Cells Source Type: research

Ancestry-specific predisposing germline variants in cancer
ConclusionsWhile several CPGs are shared across patients, many pathogenic variants are found to be ancestry-specific and trigger somatic effects. Studies using larger cohorts of diverse ancestries are required to pinpoint ancestry-specific genetic predisposition and inform genetic screening strategies. (Source: Genome Medicine)
Source: Genome Medicine - May 29, 2020 Category: Genetics & Stem Cells Source Type: research

Single-cell RNA sequencing reveals the tumor microenvironment and facilitates strategic choices to circumvent treatment failure in a chemorefractory bladder cancer patient
ConclusionWe presented a single case report demonstrating the power of scRNA-seq for visualizing the tumor microenvironment and identifying molecular and cellular therapeutic targets in a treatment-refractory cancer patient. (Source: Genome Medicine)
Source: Genome Medicine - May 27, 2020 Category: Genetics & Stem Cells Source Type: research

The rate and spectrum of mosaic mutations during embryogenesis revealed by RNA sequencing of 49 tissues
ConclusionsIn summary, our multi-tissue, multi-individual study reveals a surprisingly high number of embryonic mosaic mutations in coding regions, implying novel hypotheses and diagnostic procedures for investigating genetic causes of disease and cancer predisposition. (Source: Genome Medicine)
Source: Genome Medicine - May 27, 2020 Category: Genetics & Stem Cells Source Type: research

The Medical Genome Initiative: moving whole-genome sequencing for rare disease diagnosis to the clinic
AbstractClinical whole-genome sequencing (WGS) offers clear diagnostic benefits for patients with rare disease. However, there are barriers to its widespread adoption, including a lack of standards for clinical practice. The Medical Genome Initiative consortium was formed to provide practical guidance and support the development of standards for the use of clinical WGS. (Source: Genome Medicine)
Source: Genome Medicine - May 27, 2020 Category: Genetics & Stem Cells Source Type: research

Epigenetic deregulation of lamina-associated domains in Hutchinson-Gilford progeria syndrome
ConclusionsTaken together, our results strongly implicate epigenetic deregulation of LADs as an important and previously unrecognized feature of HGPS, which contributes to disease-specific gene expression. Therefore, they not only add a new layer to the study of epigenetic changes in the progeroid syndrome, but also advance our understanding of the disease ’s pathology at the cellular level. (Source: Genome Medicine)
Source: Genome Medicine - May 25, 2020 Category: Genetics & Stem Cells Source Type: research

MHC-I genotype and tumor mutational burden predict response to immunotherapy
ConclusionsPoor presentation of driver mutation neoantigens by MHC-I may explain why some tumors (even with a high TMB) do not respond to ICB. (Source: Genome Medicine)
Source: Genome Medicine - May 19, 2020 Category: Genetics & Stem Cells Source Type: research

Polygenic risk scores: from research tools to clinical instruments
AbstractGenome-wide association studies have shown unequivocally that common complex disorders have a polygenic genetic architecture and have enabled researchers to identify genetic variants associated with diseases. These variants can be combined into a polygenic risk score that captures part of an individual ’s susceptibility to diseases. Polygenic risk scores have been widely applied in research studies, confirming the association between the scores and disease status, but their clinical utility has yet to be established. Polygenic risk scores may be used to estimate an individual’s lifetime geneti c risk of...
Source: Genome Medicine - May 18, 2020 Category: Genetics & Stem Cells Source Type: research

CEOP/IVE/GDP alternating regimen compared with CEOP as the first-line therapy for newly diagnosed patients with peripheral T cell lymphoma: results from a phase 2, multicenter, randomized, controlled clinical trial
AbstractBackgroundCyclophosphamide, doxorubicin, vincristine, and prednisolone (CHOP)/CHOP-like chemotherapy is widely used in peripheral T cell lymphoma (PTCL). Here we conducted a phase 2, multicenter, randomized, controlled trial, comparing the efficacy and safety of CEOP/IVE/GDP alternating regimen with CEOP in newly diagnosed PTCL.MethodsPTCL patients, except for anaplastic large cell lymphoma-anaplastic lymphoma kinase positive, were 1:1 randomly assigned to receive CEOP/IVE/GDP (CEOP, cyclophosphamide 750  mg/m2, epirubicin 70  mg/m2, vincristine 1.4  mg/m2 [maximum 2  mg] on day 1, and p...
Source: Genome Medicine - April 30, 2020 Category: Genetics & Stem Cells Source Type: research

EM-mosaic detects mosaic point mutations that contribute to congenital heart disease
ConclusionsWe estimate that ~  1% of CHD probands have a mosaic variant detectable in blood that could contribute to cardiac malformations, particularly those damaging variants with relatively higher allele fraction. Although blood is a readily available DNA source, cardiac tissues analyzed contributed ~ 5% of somatic mosaic variants identified, indicating the value of tissue mosaicism analyses. (Source: Genome Medicine)
Source: Genome Medicine - April 29, 2020 Category: Genetics & Stem Cells Source Type: research

Translating insights from neuropsychiatric genetics and genomics for precision psychiatry
AbstractThe primary aim of precision medicine is to tailor healthcare more closely to the needs of individual patients. This requires progress in two areas: the development of more precise treatments and the ability to identify patients or groups of patients in the clinic for whom such treatments are likely to be the most effective. There is widespread optimism that advances in genomics will facilitate both of these endeavors. It can be argued that of all medical specialties psychiatry has most to gain in these respects, given its current reliance on syndromic diagnoses, the minimal foundation of existing mechanistic knowl...
Source: Genome Medicine - April 29, 2020 Category: Genetics & Stem Cells Source Type: research

Widespread and tissue-specific expression of endogenous retroelements in human somatic tissues
ConclusionsThis study shows that ERE expression in somatic tissues is more pervasive and heterogeneous than anticipated. The high and diversified expression of EREs in mTECs and their ability to generate MAPs suggest that EREs may play an important role in the establishment of self-tolerance. The viral-like properties of ERE-derived MAPs suggest that those not expressed in mTECs can be highly immunogenic. (Source: Genome Medicine)
Source: Genome Medicine - April 28, 2020 Category: Genetics & Stem Cells Source Type: research

Centromeric cohesion failure invokes a conserved choreography of chromosomal mis-segregations in pancreatic neuroendocrine tumor
ConclusionsWe propose an evolutionary model for a subset of aggressive PANETs that is initiated by mutation ofMEN1,ATRX, andDAXX, resulting in defects in centromere cohesion from ectopic CENP-A deposition that leads to selective loss of chromosomes and the LOH phenotype seen in late-stage metastatic PANETs. These insights aid in disease risk stratification and nominate potential therapeutic vulnerabilities to treat this disease. (Source: Genome Medicine)
Source: Genome Medicine - April 28, 2020 Category: Genetics & Stem Cells Source Type: research

Exploratory analysis of age and sex dependent DNA methylation patterns on the X-chromosome in whole blood samples
AbstractBackgroundLarge numbers of autosomal sites are found differentially methylated in the aging genome. Due to analytical difficulties in dealing with sex differences in X-chromosome content and X-inactivation (XCI) in females, this has not been explored for the X chromosome.MethodsUsing data from middle age to elderly individuals (age 55+  years) from two Danish cohorts of monozygotic twins and the Scottish Lothian Birth Cohort 1921, we conducted an X-chromosome-wide analysis of age-associated DNA methylation patterns with consideration of stably inferred XCI status.ResultsThrough analysing and comparing sex-sp...
Source: Genome Medicine - April 28, 2020 Category: Genetics & Stem Cells Source Type: research

Correction to: A validated single-cell-based strategy to identify diagnostic and therapeutic targets in complex diseases
An amendment to this paper has been published and can be accessed via the original article. (Source: Genome Medicine)
Source: Genome Medicine - April 28, 2020 Category: Genetics & Stem Cells Source Type: research

Clinical impact of splicing in neurodevelopmental disorders
AbstractClinical exome sequencing is frequently used to identify gene-disrupting variants in individuals with neurodevelopmental disorders. While splice-disrupting variants are known to contribute to these disorders, clinical interpretation of cryptic splice variants outside of the canonical splice site has been challenging. Here, we discuss papers that improve such detection. (Source: Genome Medicine)
Source: Genome Medicine - April 24, 2020 Category: Genetics & Stem Cells Source Type: research

Shallow whole-genome sequencing of plasma cell-free DNA accurately differentiates small from non-small cell lung carcinoma
ConclusionsCopy number profiling of cell-free DNA enables histological classification. Since shallow whole-genome sequencing is inexpensive and often fully operational at routine molecular laboratories, this finding has current diagnostic potential, especially for patients with lesions that are difficult to reach. (Source: Genome Medicine)
Source: Genome Medicine - April 21, 2020 Category: Genetics & Stem Cells Source Type: research

Transcriptome analysis and functional characterization of cerebral organoids in bipolar disorder
ConclusionsOur studies in cerebral organoids from bipolar disorder showed dysregulation in genes involved in cell adhesion, immune signaling, and endoplasmic reticulum biology; implicated a central role for the GWAS hit NCAN in the biology of BPI; and showed evidence of deficits in neurotransmission. (Source: Genome Medicine)
Source: Genome Medicine - April 19, 2020 Category: Genetics & Stem Cells Source Type: research

Burden of tumor mutations, neoepitopes, and other variants are weak predictors of cancer immunotherapy response and overall survival
ConclusionsWe find sufficient cause to suggest that the predictive clinical value of TMB should not be overstated or oversimplified. While it is readily quantified, TMB is at best a limited surrogate biomarker of immunotherapy response. The data do not support isolated use of TMB in renal cell carcinoma. (Source: Genome Medicine)
Source: Genome Medicine - March 30, 2020 Category: Genetics & Stem Cells Source Type: research

Integrative -omics and HLA-ligandomics analysis to identify novel drug targets for ccRCC immunotherapy
ConclusionsIntegration of HLA ligandomics, transcriptomics, genetic, and epigenetic data leads to the identification of novel functionally relevant therapeutic targets for ccRCC immunotherapy. Validation of the identified targets is recommended to expand the treatment landscape of ccRCC. (Source: Genome Medicine)
Source: Genome Medicine - March 30, 2020 Category: Genetics & Stem Cells Source Type: research

Tracking cancer progression: from circulating tumor cells to metastasis
AbstractThe analysis of circulating tumor cells (CTCs) is an outstanding tool to provide insights into the biology of metastatic cancers, to monitor disease progression and with potential for use in liquid biopsy-based personalized cancer treatment. These goals are ambitious, yet  recent studies are already allowing a sharper understanding of the strengths, challenges, and opportunities provided by liquid biopsy approaches. For instance, through single-cell-resolution genomics and transcriptomics, it is becoming increasingly clear that CTCs are heterogeneous at multiple lev els and that only a fraction of them is capa...
Source: Genome Medicine - March 19, 2020 Category: Genetics & Stem Cells Source Type: research

Clinical and molecular characterization of virus-positive and virus-negative Merkel cell carcinoma
ConclusionsThese results demonstrate the value of high-confidence virus detection for identifying molecular mechanisms of UV and viral oncogenesis in MCC. Furthermore, integrating these data with clinical data revealed features that could impact patient outcome and improve our understanding of MCC risk factors. (Source: Genome Medicine)
Source: Genome Medicine - March 18, 2020 Category: Genetics & Stem Cells Source Type: research

Methylome-based cell-of-origin modeling (Methyl-COOM) identifies aberrant expression of immune regulatory molecules in CLL
ConclusionsMethyl-COOM analysis of CLL identified disease-specific aberrant gene regulation. The aberrantly expressed genes identified in this study might play a role in immune-evasion in CLL and might serve as novel targets for immunotherapy approaches. In summary, we propose a novel framework for in silico modeling of reference DNA methylomes and for the identification of cancer-specific epigenetic changes, a concept that can be broadly applied to other human malignancies. (Source: Genome Medicine)
Source: Genome Medicine - March 18, 2020 Category: Genetics & Stem Cells Source Type: research

Gene family information facilitates variant interpretation and identification of disease-associated genes in neurodevelopmental disorders
ConclusionThis study represents the first method to incorporate gene family information into a statistical framework to interpret variant data for NDDs and to discover new NDD-associated genes. (Source: Genome Medicine)
Source: Genome Medicine - March 17, 2020 Category: Genetics & Stem Cells Source Type: research

Phylogenetically informative mutations in genes implicated in antibiotic resistance in Mycobacterium tuberculosis complex
ConclusionsOur findings underline that the genetic diversity in MTBC has to be studied more systematically to inform the design of clinical trials and to define sound epidemiologic cut-off values (ECOFFs) for new and repurposed anti-tuberculosis drugs. In that regard, our comprehensive variant catalogue provides a solid basis for the interpretation of mutations in genotypic as well as in phenotypic DST assays. (Source: Genome Medicine)
Source: Genome Medicine - March 6, 2020 Category: Genetics & Stem Cells Source Type: research

Epigenome-wide meta-analysis of blood DNA methylation in newborns and children identifies numerous loci related to gestational age
AbstractBackgroundPreterm birth and shorter duration of pregnancy are associated with increased morbidity in neonatal and later life. As the epigenome is known to have an important role during fetal development, we investigated associations between gestational age and blood DNA methylation in children.MethodsWe performed meta-analysis of Illumina ’s HumanMethylation450-array associations between gestational age and cord blood DNA methylation in 3648 newborns from 17 cohorts without common pregnancy complications, induced delivery or caesarean section. We also explored associations of gestational age with DNA methylat...
Source: Genome Medicine - March 2, 2020 Category: Genetics & Stem Cells Source Type: research

Comprehensive characterization of cell-free tumor DNA in plasma and urine of patients with renal tumors
ConclusionsThese data highlight RCC as a ctDNA-low malignancy. The biological reasons for this are yet to be determined. Nonetheless, our findings indicate potential clinical utility in the management of patients with renal tumors, provided improvement in isolation and detection approaches. (Source: Genome Medicine)
Source: Genome Medicine - February 28, 2020 Category: Genetics & Stem Cells Source Type: research

Single-cell transcriptome analysis reveals TOX as a promoting factor for T cell exhaustion and a predictor for anti-PD-1 responses in human cancer
ConclusionsWe predicted the regulatory factors involved in T cell exhaustion using single-cell transcriptome profiles of human TI lymphocytes. TOX promoted intra-tumoral CD8+ T cell exhaustion via upregulation of IC molecules. This suggested that TOX inhibition can potentially impede T cell exhaustion and improve ICI efficacy. Additionally,TOX expression in the TI T cells can be used for patient stratification during anti-tumor treatments, including anti-PD-1 immunotherapy. (Source: Genome Medicine)
Source: Genome Medicine - February 28, 2020 Category: Genetics & Stem Cells Source Type: research

A reference profile-free deconvolution method to infer cancer cell-intrinsic subtypes and tumor-type-specific stromal profiles
ConclusionsDeClust is a useful tool for cancer cell-intrinsic molecular subtyping of solid tumors. DeClust subtypes, together with the tumor-type-specific stromal profiles generated by this pan-cancer study, may lead to mechanistic and clinical insights across multiple tumor types. (Source: Genome Medicine)
Source: Genome Medicine - February 28, 2020 Category: Genetics & Stem Cells Source Type: research

Large-scale public data reuse to model immunotherapy response and resistance
AbstractDespite growing numbers of immune checkpoint blockade (ICB) trials with available omics data, it remains challenging to evaluate the robustness of ICB response and immune evasion mechanisms comprehensively. To address these challenges, we integrated large-scale omics data and biomarkers on published ICB trials, non-immunotherapy tumor profiles, and CRISPR screens on a web platform TIDE (http://tide.dfci.harvard.edu). We processed the omics data for over 33K samples in 188 tumor cohorts from public databases, 998 tumors from 12 ICB clinical studies, and eight CRISPR screens that identified gene modulators of the ant...
Source: Genome Medicine - February 26, 2020 Category: Genetics & Stem Cells Source Type: research

Cell-free DNA analysis reveals POLR1D -mediated resistance to bevacizumab in colorectal cancer
ConclusionsNon-invasive analyses of cell-free DNA from patients undergoing treatment with bevacizumab enabled the tracking of evolving tumor genomes and helped identify a recurrent focal SCNA of clinical relevance. Here, we describe a novel resistance mechanism against a widely applied treatment in patients with mCRC which will impact the clinical management of patients. (Source: Genome Medicine)
Source: Genome Medicine - February 22, 2020 Category: Genetics & Stem Cells Source Type: research

A chromosomal connectome for psychiatric and metabolic risk variants in adult dopaminergic neurons
ConclusionsWe uncovered shared nuclear topographies of cognitive and metabolic risk variants. More broadly, our PsychENCODE sponsored Hi-C study offers a novel genomic approach for the study of psychiatric and medical co-morbidities constrained by limited overlap of their respective genetic risk architectures on the linear genome. (Source: Genome Medicine)
Source: Genome Medicine - February 19, 2020 Category: Genetics & Stem Cells Source Type: research

Towards a European health research and innovation cloud (HRIC)
AbstractThe European Union (EU) initiative on the Digital Transformation of Health and Care (Digicare) aims to provide the conditions necessary for building a secure, flexible, and decentralized digital health infrastructure. Creating a European Health Research and Innovation Cloud (HRIC) within this environment should enable data sharing and analysis for health research across the EU, in compliance with data protection legislation while preserving the full trust of the participants. Such a HRIC should learn from and build on existing data infrastructures, integrate best practices, and focus on the concrete needs of the co...
Source: Genome Medicine - February 19, 2020 Category: Genetics & Stem Cells Source Type: research

Comprehensive pharmacogenomic characterization of gastric cancer
ConclusionsCollectively, our results demonstrate the feasibility of drug screening combined with tumor molecular characterization to facilitate personalized therapeutic regimens for gastric tumors. (Source: Genome Medicine)
Source: Genome Medicine - February 18, 2020 Category: Genetics & Stem Cells Source Type: research

The paradox of cancer genes in non-malignant conditions: implications for precision medicine
AbstractNext-generation sequencing has enabled patient selection for targeted drugs, some of which have shown remarkable efficacy in cancers that have the cognate molecular signatures. Intriguingly, rapidly emerging data indicate that altered genes representing oncogenic drivers can also be found in sporadic non-malignant conditions, some of which have negligible and/or low potential for transformation to cancer. For instance, activatingKRAS mutations are discerned in endometriosis and in brain arteriovenous malformations, inactivatingTP53 tumor suppressor mutations in rheumatoid arthritis synovium, andAKT,MAPK, andAMPK pa...
Source: Genome Medicine - February 17, 2020 Category: Genetics & Stem Cells Source Type: research

The pan-cancer landscape of prognostic germline variants in 10,582 patients
ConclusionsGermline variants are predictive of outcome in cancer patients and specific germline variants can improve patient outcome predictions beyond predictions made using clinical factors alone. The germline variants also implicate new means by which known oncogenes, tumor suppressor genes, and driver genes are perturbed in cancer and suggest roles in cancer for other genes that have not been extensively studied in oncology. Further studies in other cancer cohorts are necessary to confirm that germline variation is associated with outcome in cancer patients as this is a proof-of-principle study. (Source: Genome Medicine)
Source: Genome Medicine - February 17, 2020 Category: Genetics & Stem Cells Source Type: research

A highly sensitive and specific workflow for detecting rare copy-number variants from exome sequencing data
ConclusionsIn summary, we introduced a modification to the default ExomeDepth workflow to reduce the false positives originating from the repetitive regions of the genome, created a large-scale iterative variant calling framework for reproducibility, and provided recommendations for implementation in clinical settings. (Source: Genome Medicine)
Source: Genome Medicine - January 30, 2020 Category: Genetics & Stem Cells Source Type: research

A proactive genotype-to-patient-phenotype map for cystathionine beta-synthase
ConclusionsWe demonstrate that highly multiplexed cell-based assays can yield proactive maps of variant function and patient response to therapy, even for rare variants not previously seen in the clinic. (Source: Genome Medicine)
Source: Genome Medicine - January 30, 2020 Category: Genetics & Stem Cells Source Type: research

Interactions between the gut microbiome and host gene regulation in cystic fibrosis
ConclusionsIn addition to characterizing host gene expression and mucosal microbiome in cystic fibrosis patients, our study explored the potential role of host-microbe interactions in the etiology of colorectal cancer in cystic fibrosis. Our results provide biomarkers that may potentially serve as targets for stratifying risk of colorectal cancer in patients with cystic fibrosis. (Source: Genome Medicine)
Source: Genome Medicine - January 28, 2020 Category: Genetics & Stem Cells Source Type: research

Stepwise evolution and convergent recombination underlie the global dissemination of carbapenemase-producing Escherichia coli
ConclusionsLineages of CP-Ec have started to disseminate globally. However, their selection is a multistep process involving mutations, recombination, acquisition of antibiotic resistance genes, and selection by β-lactams from diverse families. This process did not yet occur in the high-risk lineage ST131. (Source: Genome Medicine)
Source: Genome Medicine - January 20, 2020 Category: Genetics & Stem Cells Source Type: research

Genomic surveillance for hypervirulence and multi-drug resistance in invasive Klebsiella pneumoniae from South and Southeast Asia
ConclusionsK. pneumoniae BSI in South and Southeast Asia are caused by different STs from those predominating in other regions, and with higher frequency of acquired virulence determinants.K. pneumoniae carrying bothiuc and AMR genes were also detected at higher rates than have been reported elsewhere. The study demonstrates how genomics-based surveillance —reporting full molecular profiles including STs, AMR, virulence and serotype locus information—can help standardise comparisons between sites and identify regional differences in pathogen populations. (Source: Genome Medicine)
Source: Genome Medicine - January 16, 2020 Category: Genetics & Stem Cells Source Type: research

De novo variants in exomes of congenital heart disease patients identify risk genes and pathways
ConclusionsUltimately, these findings suggest novel genes that are likely to be contributing to CHD pathogenesis. (Source: Genome Medicine)
Source: Genome Medicine - January 15, 2020 Category: Genetics & Stem Cells Source Type: research

Molecular profiling for precision cancer therapies
We describe novel molecular characterization strategies beyond tumor DNA sequencing, such as transcriptomics, immunophenotyping, epigenetic profiling, and single-cell analyses. We also review current and potential applications of liquid biopsies to evaluate blood-based biomarkers, such as circulating tumor cells and circulating nucleic acids. Last, lessons learned from the existing limitations of genotype-derived therapies provide insights into ways to expand precision medicine beyond genomics. (Source: Genome Medicine)
Source: Genome Medicine - January 14, 2020 Category: Genetics & Stem Cells Source Type: research