A reference profile-free deconvolution method to infer cancer cell-intrinsic subtypes and tumor-type-specific stromal profiles
Patient stratification based on molecular subtypes is an important strategy for cancer precision medicine. Deriving clinically informative cancer molecular subtypes from transcriptomic data generated on whole ...Genome Medicine 2020 12:24Comprehensive characterization of cell-free tumor DNA in plasma and urine of patients with renal tumors
Cell-free tumor-derived DNA (ctDNA) allows non-invasive monitoring of cancers, but its utility in renal cell cancer (RCC) has not been established.Genome Medicine 2020 12:23Single-cell transcriptome analysis reveals TOX as a promoting factor for T cell exhaustion and a predictor for anti-PD-1 responses in human cancer
T cells exhibit heterogeneous functional states in the tumor microenvironment. Immune checkpoint inhibitors (ICIs) can reinvigorate only the stem cell-like progenitor exhausted T cells, which suggests that inh...Genome Medicine 2020 12:22Large-scale public data reuse to model immunotherapy response and resistance
Despite 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...Genome Medicine 2020 12:21Cell-free DNA analysis reveals POLR1D-mediated resistance to bevacizumab in colorectal cancer
Bevacizumab, a monoclonal antibody against soluble VEGFA, is an approved and commonly administered anti-angiogenic drug in patients with metastasized colorectal cancer (mCRC). The survival benefit of anti-VEGF...Genome Medicine 2020 12:20A chromosomal connectome for psychiatric and metabolic risk variants in adult dopaminergic neurons
Midbrain dopaminergic neurons (MDN) represent 0.0005% of the brain’s neuronal population and mediate cognition, food intake, and metabolism. MDN are also posited to underlay the neurobiological dysfunction of ...Genome Medicine 2020 12:19Towards a European health research and innovation cloud (HRIC)
The 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 infrast...Genome Medicine 2020 12:18Comprehensive pharmacogenomic characterization of gastric cancer
Gastric cancer is among the most lethal human malignancies. Previous studies have identified molecular aberrations that constitute dynamic biological networks and genomic complexities of gastric tumors. Howeve...Genome Medicine 2020 12:17The paradox of cancer genes in non-malignant conditions: implications for precision medicine
Next-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 d...Genome Medicine 2020 12:16The pan-cancer landscape of prognostic germline variants in 10,582 patients
While clinical factors such as age, grade, stage, and histological subtype provide physicians with information about patient prognosis, genomic data can further improve these predictions. Previous studies have...Genome Medicine 2020 12:15A highly sensitive and specific workflow for detecting rare copy-number variants from exome sequencing data
Exome sequencing (ES) is a first-tier diagnostic test for many suspected Mendelian disorders. While it is routine to detect small sequence variants, it is not a standard practice in clinical settings to detect...Genome Medicine 2020 12:14A proactive genotype-to-patient-phenotype map for cystathionine beta-synthase
For the majority of rare clinical missense variants, pathogenicity status cannot currently be classified. Classical homocystinuria, characterized by elevated homocysteine in plasma and urine, is caused by vari...Genome Medicine 2020 12:13Interactions between the gut microbiome and host gene regulation in cystic fibrosis
Cystic fibrosis is the most common autosomal recessive genetic disease in Caucasians. It is caused by mutations in the CFTR gene, leading to poor hydration of mucus and impairment of the respiratory, digestive, a...Genome Medicine 2020 12:12Stepwise evolution and convergent recombination underlie the global dissemination of carbapenemase-producing Escherichia coli
Carbapenem-resistant Enterobacteriaceae are considered by WHO as “critical” priority pathogens for which novel antibiotics are urgently needed. The dissemination of carbapenemase-producing Escherichia coli (CP-EcGenome Medicine 2020 12:10Genomic surveillance for hypervirulence and multi-drug resistance in invasive Klebsiella pneumoniae from South and Southeast Asia
Klebsiella pneumoniae is a leading cause of bloodstream infection (BSI). Strains producing extended-spectrum beta-lactamases (ESBLs) or carbapenemases are considered global priority pathogens for which new treatm...Genome Medicine 2020 12:11De novo variants in exomes of congenital heart disease patients identify risk genes and pathways
Congenital heart disease (CHD) affects ~ 1% of live births and is the most common birth defect. Although the genetic contribution to the CHD has been long suspected, it has only been well established recently....Genome Medicine 2020 12:9Molecular profiling for precision cancer therapies
The number of druggable tumor-specific molecular aberrations has grown substantially in the past decade, with a significant survival benefit obtained from biomarker matching therapies in several cancer types. ...Genome Medicine 2020 12:8An unsupervised learning approach to identify novel signatures of health and disease from multimodal data
Modern medicine is rapidly moving towards a data-driven paradigm based on comprehensive multimodal health assessments. Integrated analysis of data from different modalities has the potential of uncovering nove...Genome Medicine 2020 12:7Strains used in whole organism Plasmodium falciparum vaccine trials differ in genome structure, sequence, and immunogenic potential
Plasmodium falciparum (Pf) whole-organism sporozoite vaccines have been shown to provide significant protection against controlled human malaria infection (CHMI) in clinical trials. Initial CHMI studies showed si...Genome Medicine 2020 12:6- Genome Medicine 2019 12:5
Digital twins to personalize medicine
Personalized medicine requires the integration and processing of vast amounts of data. Here, we propose a solution to this challenge that is based on constructing Digital Twins. These are high-resolution model...Genome Medicine 2019 12:4Recommendations for application of the functional evidence PS3/BS3 criterion using the ACMG/AMP sequence variant interpretation framework
The American College of Medical Genetics and Genomics (ACMG)/Association for Molecular Pathology (AMP) clinical variant interpretation guidelines established criteria for different types of evidence. This incl...Genome Medicine 2019 12:3Exome sequencing reveals a high prevalence of BRCA1 and BRCA2 founder variants in a diverse population-based biobank
Pathogenic variants in BRCA1 and BRCA2 (BRCA1/2) lead to increased risk of breast, ovarian, and other cancers, but most variant-positive individuals in the general population are unaware of their risk, and little...Genome Medicine 2019 12:2An epigenome-wide association study of sex-specific chronological ageing
Advanced age is associated with cognitive and physical decline and is a major risk factor for a multitude of disorders. There is also a gap in life expectancy between males and females. DNA methylation differe...Genome Medicine 2019 12:1Neoantigen-specific immunity in low mutation burden colorectal cancers of the consensus molecular subtype 4
The efficacy of checkpoint blockade immunotherapies in colorectal cancer is currently restricted to a minority of patients diagnosed with mismatch repair-deficient tumors having high mutation burden. However, ...Genome Medicine 2019 11:87Epigenetic therapy of myelodysplastic syndromes connects to cellular differentiation independently of endogenous retroelement derepression
Myelodysplastic syndromes (MDS) and acute myeloid leukaemia (AML) are characterised by abnormal epigenetic repression and differentiation of bone marrow haematopoietic stem cells (HSCs). Drugs that reverse epi...Genome Medicine 2019 11:86Recommendations for the collection and use of multiplexed functional data for clinical variant interpretation
Variants of uncertain significance represent a massive challenge to medical genetics. Multiplexed functional assays, in which the functional effects of thousands of genomic variants are assessed simultaneously...Genome Medicine 2019 11:85A KHDC3L mutation resulting in recurrent hydatidiform mole causes genome-wide DNA methylation loss in oocytes and persistent imprinting defects post-fertilisation
Maternal effect mutations in the components of the subcortical maternal complex (SCMC) of the human oocyte can cause early embryonic failure, gestational abnormalities and recurrent pregnancy loss. Enigmatical...Genome Medicine 2019 11:84Re-analysis of whole-exome sequencing data uncovers novel diagnostic variants and improves molecular diagnostic yields for sudden death and idiopathic diseases
Whole-exome sequencing (WES) has become an efficient diagnostic test for patients with likely monogenic conditions such as rare idiopathic diseases or sudden unexplained death. Yet, many cases remain undiagnos...Genome Medicine 2019 11:83Genomics of circadian rhythms in health and disease
Circadian clocks are endogenous oscillators that control 24-h physiological and behavioral processes. The central circadian clock exerts control over myriad aspects of mammalian physiology, including the regul...Genome Medicine 2019 11:82FIREVAT: finding reliable variants without artifacts in human cancer samples using etiologically relevant mutational signatures
Accurate identification of real somatic variants is a primary part of cancer genome studies and precision oncology. However, artifacts introduced in various steps of sequencing obfuscate confidence in variant ...Genome Medicine 2019 11:81Distinct patterns of complex rearrangements and a mutational signature of microhomeology are frequently observed in PLP1 copy number gain structural variants
We investigated the features of the genomic rearrangements in a cohort of 50 male individuals with proteolipid protein 1 (PLP1) copy number gain events who were ascertained with Pelizaeus-Merzbacher disease (PMD;...Genome Medicine 2019 11:80Prioritization of genes driving congenital phenotypes of patients with de novo genomic structural variants
Genomic structural variants (SVs) can affect many genes and regulatory elements. Therefore, the molecular mechanisms driving the phenotypes of patients carrying de novo SVs are frequently unknown.Genome Medicine 2019 11:79Text-mining clinically relevant cancer biomarkers for curation into the CIViC database
Precision oncology involves analysis of individual cancer samples to understand the genes and pathways involved in the development and progression of a cancer. To improve patient care, knowledge of diagnostic,...Genome Medicine 2019 11:78Comparative analysis of functional assay evidence use by ClinGen Variant Curation Expert Panels
The 2015 American College of Medical Genetics and Genomics (ACMG) and the Association for Molecular Pathology (AMP) guidelines for clinical sequence variant interpretation state that “well-established” functio...Genome Medicine 2019 11:77Standard operating procedure for curation and clinical interpretation of variants in cancer
Manually curated variant knowledgebases and their associated knowledge models are serving an increasingly important role in distributing and interpreting variants in cancer. These knowledgebases vary in their ...Genome Medicine 2019 11:76Genomic screening and genomic diagnostic testing—two very different kettles of fish
Genomic testing can be misunderstood as being determinative, when in reality it is the same as all other tests and context is essential for its correct interpretation. Two hypothetical cases of testing for Mar...Genome Medicine 2019 11:75Low coverage whole genome sequencing enables accurate assessment of common variants and calculation of genome-wide polygenic scores
Inherited susceptibility to common, complex diseases may be caused by rare, pathogenic variants (“monogenic”) or by the cumulative effect of numerous common variants (“polygenic”). Comprehensive genome interpr...Genome Medicine 2019 11:74Immune receptor repertoires in pediatric and adult acute myeloid leukemia
Acute myeloid leukemia (AML), caused by the abnormal proliferation of immature myeloid cells in the blood or bone marrow, is one of the most common hematologic malignancies. Currently, the interactions between...Genome Medicine 2019 11:73Is ‘likely pathogenic’ really 90% likely? Reclassification data in ClinVar
In 2015, professional guidelines defined the term ‘likely pathogenic’ to mean with a 90% chance of pathogenicity. To determine whether current practice reflects this definition, ClinVar classifications were tr...Genome Medicine 2019 11:72Neoantigens and genome instability: impact on immunogenomic phenotypes and immunotherapy response
The resurgence of immune therapies in cancer medicine has elicited a corresponding interest in understanding the basis of patient response or resistance to these treatments. One aspect of patient response clea...Genome Medicine 2019 11:71Artificial intelligence in clinical and genomic diagnostics
Artificial intelligence (AI) is the development of computer systems that are able to perform tasks that normally require human intelligence. Advances in AI software and hardware, especially deep learning algor...Genome Medicine 2019 11:70
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