1,140 results match your criteria Genome Medicine [Journal]


TCF21 and AP-1 interact through epigenetic modifications to regulate coronary artery disease gene expression.

Genome Med 2019 May 2;11(1):23. Epub 2019 May 2.

Division of Cardiovascular Medicine and Cardiovascular Institute, School of Medicine, Stanford University, 300 Pasteur Dr., Falk CVRC, Stanford, CA, 94305, USA.

Background: Genome-wide association studies have identified over 160 loci that are associated with coronary artery disease. As with other complex human diseases, risk in coronary disease loci is determined primarily by altered expression of the causal gene, due to variation in binding of transcription factors and chromatin-modifying proteins that directly regulate the transcriptional apparatus. We have previously identified a coronary disease network downstream of the disease-associated transcription factor TCF21, and in work reported here extends these studies to investigate the mechanisms by which it interacts with the AP-1 transcription complex to regulate local epigenetic effects in these downstream coronary disease loci. Read More

View Article

Download full-text PDF

Source
http://dx.doi.org/10.1186/s13073-019-0635-9DOI Listing

Interchromosomal template-switching as a novel molecular mechanism for imprinting perturbations associated with Temple syndrome.

Genome Med 2019 Apr 23;11(1):25. Epub 2019 Apr 23.

Department of Molecular and Human Genetics, Baylor College of Medicine, One Baylor Plaza, Room 604B, Houston, TX, 77030-3498, USA.

Background: Intrachromosomal triplications (TRP) can contribute to disease etiology via gene dosage effects, gene disruption, position effects, or fusion gene formation. Recently, post-zygotic de novo triplications adjacent to copy-number neutral genomic intervals with runs of homozygosity (ROH) have been shown to result in uniparental isodisomy (UPD). The genomic structure of these complex genomic rearrangements (CGRs) shows a consistent pattern of an inverted triplication flanked by duplications (DUP-TRP/INV-DUP) formed by an iterative DNA replisome template-switching mechanism during replicative repair of a single-ended, double-stranded DNA (seDNA), the ROH results from an interhomolog or nonsister chromatid template switch. Read More

View Article

Download full-text PDF

Source
http://dx.doi.org/10.1186/s13073-019-0633-yDOI Listing

Molecular basis for phenotypic similarity of genetic disorders.

Genome Med 2019 Apr 23;11(1):24. Epub 2019 Apr 23.

Bioinformatics and Genomics Program, The Huck Institutes of the Life Sciences, Pennsylvania State University, University Park, PA, 16802, USA.

The contribution of distinct genes to overlapping phenotypes suggests that such genes share ancestral origins, membership of disease pathways, or molecular functions. A recent study by Liu and colleagues identified mutations in TCF20, a paralog of RAI1, among individuals manifesting a novel syndrome that has phenotypes similar to those of Smith-Magenis syndrome (a disorder caused by disruption of RAI1). 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. Read More

View Article

Download full-text PDF

Source
http://dx.doi.org/10.1186/s13073-019-0641-yDOI Listing

Designing circulating tumor DNA-based interventional clinical trials in oncology.

Genome Med 2019 Apr 19;11(1):22. Epub 2019 Apr 19.

Division of Medical Oncology and Hematology, Princess Margaret Cancer Centre, University of Toronto, Toronto, Ontario, Canada.

Circulating 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. Read More

View Article

Download full-text PDF

Source
https://genomemedicine.biomedcentral.com/articles/10.1186/s1
Publisher Site
http://dx.doi.org/10.1186/s13073-019-0634-xDOI Listing
April 2019
1 Read

CRISPR-SONIC: targeted somatic oncogene knock-in enables rapid in vivo cancer modeling.

Genome Med 2019 Apr 16;11(1):21. Epub 2019 Apr 16.

RNA Therapeutics Institute, University of Massachusetts Medical School, Worcester, MA, 01605, USA.

CRISPR/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. Read More

View Article

Download full-text PDF

Source
http://dx.doi.org/10.1186/s13073-019-0627-9DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6466773PMC
April 2019
1 Read
4.942 Impact Factor

Translating insights into tumor evolution to clinical practice: promises and challenges.

Genome Med 2019 03 29;11(1):20. Epub 2019 Mar 29.

The Francis Crick Institute, 1 Midland Road, London, NW1 1AT, UK.

Accelerating 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. Read More

View Article

Download full-text PDF

Source
https://genomemedicine.biomedcentral.com/articles/10.1186/s1
Publisher Site
http://dx.doi.org/10.1186/s13073-019-0632-zDOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6440005PMC
March 2019
5 Reads

Developing a network view of type 2 diabetes risk pathways through integration of genetic, genomic and functional data.

Genome Med 2019 03 26;11(1):19. Epub 2019 Mar 26.

Wellcome Centre for Human Genetics, University of Oxford, Oxford, UK.

Background: Genome-wide association studies (GWAS) have identified several hundred susceptibility loci for type 2 diabetes (T2D). One critical, but unresolved, issue concerns the extent to which the mechanisms through which these diverse signals influencing T2D predisposition converge on a limited set of biological processes. However, the causal variants identified by GWAS mostly fall into a non-coding sequence, complicating the task of defining the effector transcripts through which they operate. Read More

View Article

Download full-text PDF

Source
http://dx.doi.org/10.1186/s13073-019-0628-8DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6436236PMC
March 2019
4.942 Impact Factor

Encircling the regions of the pharmacogenomic landscape that determine drug response.

Genome Med 2019 03 26;11(1):17. Epub 2019 Mar 26.

Joint IRB-BSC-CRG Program in Computational Biology, Institute for Research in Biomedicine (IRB Barcelona), The Barcelona Institute of Science and Technology, Barcelona, Catalonia, Spain.

Background: The integration of large-scale drug sensitivity screens and genome-wide experiments is changing the field of pharmacogenomics, revealing molecular determinants of drug response without the need for previous knowledge about drug action. In particular, transcriptional signatures of drug sensitivity may guide drug repositioning, prioritize drug combinations, and point to new therapeutic biomarkers. However, the inherent complexity of transcriptional signatures, with thousands of differentially expressed genes, makes them hard to interpret, thus giving poor mechanistic insights and hampering translation to clinics. Read More

View Article

Download full-text PDF

Source
http://dx.doi.org/10.1186/s13073-019-0626-xDOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6436215PMC

Loss of BAP1 as a candidate predictive biomarker for immunotherapy of mesothelioma.

Genome Med 2019 03 26;11(1):18. Epub 2019 Mar 26.

Department of Medicine, Memorial Sloan Kettering Cancer Center, 1275 York Avenue, New York, NY, 10065, USA.

As 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 that BAP1 status might identify PeM, and possibly PlM, patients who would benefit from ICI therapy. Read More

View Article

Download full-text PDF

Source
http://dx.doi.org/10.1186/s13073-019-0631-0DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6436227PMC
March 2019
1 Read

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.

Genome Med 2019 03 25;11(1):16. Epub 2019 Mar 25.

Baylor Genetics, Houston, TX, 77021, USA.

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. Read More

View Article

Download full-text PDF

Source
http://dx.doi.org/10.1186/s13073-019-0630-1DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6434874PMC
March 2019
5 Reads
4.942 Impact Factor

Circular RNAs as promising biomarkers in cancer: detection, function, and beyond.

Authors:
Shengli Li Leng Han

Genome Med 2019 03 20;11(1):15. Epub 2019 Mar 20.

Department of Biochemistry and Molecular Biology, McGovern Medical School at The University of Texas Health Science Center at Houston, Houston, TX, 77030, USA.

Circular 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 contribution of circRNAs to disease. Read More

View Article

Download full-text PDF

Source
https://genomemedicine.biomedcentral.com/articles/10.1186/s1
Publisher Site
http://dx.doi.org/10.1186/s13073-019-0629-7DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6427893PMC
March 2019
3 Reads

Correction to: NSAID use and somatic exomic mutations in Barrett's esophagus.

Genome Med 2019 03 12;11(1):14. Epub 2019 Mar 12.

Division of Human Biology, Fred Hutchinson Cancer Research Center, PO Box 19024, 1100 Fairview Ave N, Seattle, WA, 98109-1024, USA.

It was highlighted that in the original article [1] the Availability of data and materials section was incorrect. Read More

View Article

Download full-text PDF

Source
http://dx.doi.org/10.1186/s13073-019-0625-yDOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6417226PMC

De novo and inherited TCF20 pathogenic variants are associated with intellectual disability, dysmorphic features, hypotonia, and neurological impairments with similarities to Smith-Magenis syndrome.

Genome Med 2019 02 28;11(1):12. Epub 2019 Feb 28.

Baylor Genetics, Houston, TX, 77021, USA.

Background: Neurodevelopmental disorders are genetically and phenotypically heterogeneous encompassing developmental delay (DD), intellectual disability (ID), autism spectrum disorders (ASDs), structural brain abnormalities, and neurological manifestations with variants in a large number of genes (hundreds) associated. To date, a few de novo mutations potentially disrupting TCF20 function in patients with ID, ASD, and hypotonia have been reported. TCF20 encodes a transcriptional co-regulator structurally related to RAI1, the dosage-sensitive gene responsible for Smith-Magenis syndrome (deletion/haploinsufficiency) and Potocki-Lupski syndrome (duplication/triplosensitivity). Read More

View Article

Download full-text PDF

Source
http://dx.doi.org/10.1186/s13073-019-0623-0DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6393995PMC
February 2019
2 Reads
4.942 Impact Factor

A decade of Genome Medicine: toward precision medicine.

Authors:
Rabia Begum

Genome Med 2019 02 28;11(1):13. Epub 2019 Feb 28.

Genome Medicine, London, UK.

View Article

Download full-text PDF

Source
http://dx.doi.org/10.1186/s13073-019-0624-zDOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6394063PMC
February 2019

Predispositional genome sequencing in healthy adults: design, participant characteristics, and early outcomes of the PeopleSeq Consortium.

Genome Med 2019 02 27;11(1):10. Epub 2019 Feb 27.

Division of Genetics, Department of Medicine, Brigham and Women's Hospital, 41 Avenue Louis Pasteur, Suite 301, Boston, MA, 02115, USA.

Background: Increasing 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.

Methods: Apparently healthy adults who participated in four of the sequencing projects in the Consortium were included. Read More

View Article

Download full-text PDF

Source
http://dx.doi.org/10.1186/s13073-019-0619-9DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6391825PMC
February 2019

Impact of the gut microbiome on the genome and epigenome of colon epithelial cells: contributions to colorectal cancer development.

Genome Med 2019 02 25;11(1):11. Epub 2019 Feb 25.

Department of Medicine, Johns Hopkins University School of Medicine, Orleans Street, Baltimore, MD, 21231, USA.

In 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 levels that trigger and propagate tumor growth. Read More

View Article

Download full-text PDF

Source
http://dx.doi.org/10.1186/s13073-019-0621-2DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6388476PMC
February 2019

Translating genomic medicine to the clinic: challenges and opportunities.

Genome Med 2019 02 22;11(1). Epub 2019 Feb 22.

Centre for Personalised Medicine, Linköping University, Linköping, Sweden.

Genomic 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. Read More

View Article

Download full-text PDF

Source
http://dx.doi.org/10.1186/s13073-019-0622-1DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6385380PMC
February 2019

BAP1 haploinsufficiency predicts a distinct immunogenic class of malignant peritoneal mesothelioma.

Genome Med 2019 02 18;11(1). Epub 2019 Feb 18.

Vancouver Prostate Centre, 2660 Oak St, Vancouver, BC, V6H 3Z6, Canada.

Background: Malignant peritoneal mesothelioma (PeM) is a rare and fatal cancer that originates from the peritoneal lining of the abdomen. Standard treatment of PeM is limited to cytoreductive surgery and/or chemotherapy, and no effective targeted therapies for PeM exist. Some immune checkpoint inhibitor studies of mesothelioma have found positivity to be associated with a worse prognosis. Read More

View Article

Download full-text PDF

Source
http://dx.doi.org/10.1186/s13073-019-0620-3DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6378747PMC
February 2019
4 Reads

Ten years of Genome Medicine.

Genome Med 2019 02 15;11(1). Epub 2019 Feb 15.

Dr Margarete Fischer-Bosch Institute of Clinical Pharmacology, Auerbachstraße, 70376, Stuttgart, Germany.

View Article

Download full-text PDF

Source
http://dx.doi.org/10.1186/s13073-019-0618-xDOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6376775PMC
February 2019
4 Reads

Prioritizing putative influential genes in cardiovascular disease susceptibility by applying tissue-specific Mendelian randomization.

Genome Med 2019 01 31;11(1). Epub 2019 Jan 31.

MRC Integrative Epidemiology Unit, Bristol Medical School (Population Health Sciences), University of Bristol, Oakfield House, Oakfield Grove, Bristol, BS8 2BN, UK.

Background: The extent to which changes in gene expression can influence cardiovascular disease risk across different tissue types has not yet been systematically explored. We have developed an analysis pipeline that integrates tissue-specific gene expression, Mendelian randomization and multiple-trait colocalization to develop functional mechanistic insight into the causal pathway from a genetic variant to a complex trait.

Methods: We undertook an expression quantitative trait loci-wide association study to uncover genetic variants associated with both nearby gene expression and cardiovascular traits. Read More

View Article

Download full-text PDF

Source
http://dx.doi.org/10.1186/s13073-019-0613-2DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6354354PMC
January 2019

From genome integrity to cancer.

Genome Med 2019 01 29;11(1). Epub 2019 Jan 29.

Department of Medical Genetics, Addenbrooke's Treatment Centre, The Clinical School, Cambridge Biomedical Campus, Cambridge, CB2 0QQ, UK.

View Article

Download full-text PDF

Source
http://dx.doi.org/10.1186/s13073-019-0617-yDOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6350375PMC
January 2019

Quantitative approaches to variant classification increase the yield and precision of genetic testing in Mendelian diseases: the case of hypertrophic cardiomyopathy.

Genome Med 2019 01 29;11(1). Epub 2019 Jan 29.

Cardiovascular Research Centre, Cardiovascular Genetics and Genomics group at Royal Brompton Hospital and Harefield NHS Foundation Trust, Sydney Street, London, SW3 6NP, UK.

Background: International guidelines for variant interpretation in Mendelian disease set stringent criteria to report a variant as (likely) pathogenic, prioritising control of false-positive rate over test sensitivity and diagnostic yield. Genetic testing is also more likely informative in individuals with well-characterised variants from extensively studied European-ancestry populations. Inherited cardiomyopathies are relatively common Mendelian diseases that allow empirical calibration and assessment of this framework. Read More

View Article

Download full-text PDF

Source
https://genomemedicine.biomedcentral.com/articles/10.1186/s1
Publisher Site
http://dx.doi.org/10.1186/s13073-019-0616-zDOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6350371PMC
January 2019
8 Reads

Single-cell analysis reveals congruence between kidney organoids and human fetal kidney.

Genome Med 2019 01 23;11(1). Epub 2019 Jan 23.

Department of Anatomy & Neuroscience, University of Melbourne, Melbourne, VIC, Australia.

Background: Human kidney organoids hold promise for studying development, disease modelling and drug screening. However, the utility of stem cell-derived kidney tissues will depend on how faithfully these replicate normal fetal development at the level of cellular identity and complexity.

Methods: Here, we present an integrated analysis of single cell datasets from human kidney organoids and human fetal kidney to assess similarities and differences between the component cell types. Read More

View Article

Download full-text PDF

Source
http://dx.doi.org/10.1186/s13073-019-0615-0DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6345028PMC
January 2019
3 Reads

Reconstruction of full-length circular RNAs enables isoform-level quantification.

Genome Med 2019 01 19;11(1). Epub 2019 Jan 19.

Computational Genomics Lab, Beijing Institutes of Life Science, Chinese Academy of Sciences, Beijing, 100101, China.

Currently, circRNA studies are shifting from the identification of circular transcripts to understanding their biological functions. However, such endeavors have been limited by large-scale determination of their full-length sequences and also by the inability of accurate quantification at the isoform level. Here, we propose a new feature, reverse overlap (RO), for circRNA detection, which outperforms back-splice junction (BSJ)-based methods in identifying low-abundance circRNAs. Read More

View Article

Download full-text PDF

Source
http://dx.doi.org/10.1186/s13073-019-0614-1DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6339429PMC
January 2019
1 Read

Next Generation-Targeted Amplicon Sequencing (NG-TAS): an optimised protocol and computational pipeline for cost-effective profiling of circulating tumour DNA.

Genome Med 2019 01 4;11(1). Epub 2019 Jan 4.

Department of Oncology and Cancer Research UK Cambridge Institute, Li Ka Shing Centre, University of Cambridge, Cambridge, CB2 0RE, UK.

Circulating tumour DNA (ctDNA) detection and monitoring have enormous potential clinical utility in oncology. We describe here a fast, flexible and cost-effective method to profile multiple genes simultaneously in low input cell-free DNA (cfDNA): Next Generation-Targeted Amplicon Sequencing (NG-TAS). We designed a panel of 377 amplicons spanning 20 cancer genes and tested the NG-TAS pipeline using cell-free DNA from two HapMap lymphoblastoid cell lines. Read More

View Article

Download full-text PDF

Source
https://genomemedicine.biomedcentral.com/articles/10.1186/s1
Publisher Site
http://dx.doi.org/10.1186/s13073-018-0611-9DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6320579PMC
January 2019
22 Reads

Mechanisms of PARP inhibitor resistance in cancer and insights into the DNA damage response.

Genome Med 2018 12 28;10(1):101. Epub 2018 Dec 28.

Institute of Animal Pathology, Vetsuisse Faculty, Länggassstrasse, University of Bern, 3012, Bern, Switzerland.

Inhibitors of poly(ADP-ribose) polymerase (PARPi) have entered the clinic for the treatment of patients with cancers that lack homology-directed DNA repair, but drug resistance remains a clinical hurdle. Recent advances in the identification of PARPi resistance mechanisms have yielded a better understanding of DNA end protection and the relevance of endogenous poly(ADP-ribose) glycohydrolase, highlighting new vulnerabilities. Read More

View Article

Download full-text PDF

Source
http://dx.doi.org/10.1186/s13073-018-0612-8DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6309079PMC
December 2018
1 Read

Polygenic risk scores: a biased prediction?

Genome Med 2018 12 27;10(1):100. Epub 2018 Dec 27.

Department of Biomedical Data Science, Stanford University School of Medicine, Campus Drive, Stanford, CA, 94305, USA.

A new study highlights the biases and inaccuracies of polygenic risk scores (PRS) when predicting disease risk in individuals from populations other than those used in their derivation. The design bias of workhorse tools used for research, particularly genotyping arrays, contributes to these distortions. To avoid further inequities in health outcomes, the inclusion of diverse populations in research, unbiased genotyping, and methods of bias reduction in PRS are critical. Read More

View Article

Download full-text PDF

Source
http://dx.doi.org/10.1186/s13073-018-0610-xDOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6309089PMC
December 2018
2 Reads

Prevalence of pathogenic/likely pathogenic variants in the 24 cancer genes of the ACMG Secondary Findings v2.0 list in a large cancer cohort and ethnicity-matched controls.

Genome Med 2018 12 24;10(1):99. Epub 2018 Dec 24.

Clinical Genetics Branch, Division of Cancer Epidemiology and Genetics, National Cancer Institute, NIH, Rockville, MD, 20850, USA.

Background: Prior research has established that the prevalence of pathogenic/likely pathogenic (P/LP) variants across all of the American College of Medical Genetics (ACMG) Secondary Findings (SF) genes is approximately 0.8-5%. We investigated the prevalence of P/LP variants in the 24 ACMG SF v2. Read More

View Article

Download full-text PDF

Source
http://dx.doi.org/10.1186/s13073-018-0607-5DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6305568PMC
December 2018
13 Reads
4.942 Impact Factor

Emerging evidence linking the gut microbiome to neurologic disorders.

Genome Med 2018 12 21;10(1):98. Epub 2018 Dec 21.

Division of Biology and Biological Engineering, California Institute of Technology, East California Boulevard, Pasadena, CA, 91125, USA.

The gut microbiome contributes to the development and function of the immune, metabolic, and nervous systems. Furthermore, commensal bacteria modulate symptoms and pathology in mouse models of neuropsychiatric and neurodevelopmental diseases. Uncovering mechanisms that are utilized by the microbiome to mediate gut-brain connections may provide novel opportunities to target therapies to the gut in order to treat neurologic disorders. Read More

View Article

Download full-text PDF

Source
http://dx.doi.org/10.1186/s13073-018-0609-3DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6302417PMC
December 2018
2 Reads

Meta-analysis of Immunochip data of four autoimmune diseases reveals novel single-disease and cross-phenotype associations.

Genome Med 2018 12 20;10(1):97. Epub 2018 Dec 20.

Instituto de Parasitología y Biomedicina "López-Neyra", CSIC, PTS Granada, Granada, Spain.

Background: In recent years, research has consistently proven the occurrence of genetic overlap across autoimmune diseases, which supports the existence of common pathogenic mechanisms in autoimmunity. The objective of this study was to further investigate this shared genetic component.

Methods: For this purpose, we performed a cross-disease meta-analysis of Immunochip data from 37,159 patients diagnosed with a seropositive autoimmune disease (11,489 celiac disease (CeD), 15,523 rheumatoid arthritis (RA), 3477 systemic sclerosis (SSc), and 6670 type 1 diabetes (T1D)) and 22,308 healthy controls of European origin using the R package ASSET. Read More

View Article

Download full-text PDF

Source
http://dx.doi.org/10.1186/s13073-018-0604-8DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6302306PMC
December 2018
5 Reads

An integrative approach for building personalized gene regulatory networks for precision medicine.

Genome Med 2018 12 19;10(1):96. Epub 2018 Dec 19.

Department of Genetics, 5th floor ERIBA building, Antonius Deusinglaan 1, 9713AV Groningen, University of Groningen, University Medical Center Groningen, Groningen, The Netherlands.

Only a small fraction of patients respond to the drug prescribed to treat their disease, which means that most are at risk of unnecessary exposure to side effects through ineffective drugs. This inter-individual variation in drug response is driven by differences in gene interactions caused by each patient's genetic background, environmental exposures, and the proportions of specific cell types involved in disease. These gene interactions can now be captured by building gene regulatory networks, by taking advantage of RNA velocity (the time derivative of the gene expression state), the ability to study hundreds of thousands of cells simultaneously, and the falling price of single-cell sequencing. Read More

View Article

Download full-text PDF

Source
https://genomemedicine.biomedcentral.com/articles/10.1186/s1
Publisher Site
http://dx.doi.org/10.1186/s13073-018-0608-4DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6299585PMC
December 2018
11 Reads

Complex structural variants in Mendelian disorders: identification and breakpoint resolution using short- and long-read genome sequencing.

Genome Med 2018 12 7;10(1):95. Epub 2018 Dec 7.

Department of Haematology, University of Cambridge, NHS Blood and Transplant Centre, Cambridge, CB2 0PT, UK.

Background: Studies have shown that complex structural variants (cxSVs) contribute to human genomic variation and can cause Mendelian disease. We aimed to identify cxSVs relevant to Mendelian disease using short-read whole-genome sequencing (WGS), resolve the precise variant configuration and investigate possible mechanisms of cxSV formation.

Methods: We performed short-read WGS and analysis of breakpoint junctions to identify cxSVs in a cohort of 1324 undiagnosed rare disease patients. Read More

View Article

Download full-text PDF

Source
http://dx.doi.org/10.1186/s13073-018-0606-6DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6286558PMC
December 2018
2 Reads

Integrated proteotranscriptomics of breast cancer reveals globally increased protein-mRNA concordance associated with subtypes and survival.

Genome Med 2018 12 3;10(1):94. Epub 2018 Dec 3.

Molecular Epidemiology Section, Laboratory of Human Carcinogenesis, Center for Cancer Research (CCR), National Cancer Institute (NCI), National Institutes of Health (NIH), Bldg.37/Room 3050B, Bethesda, MD, 20892-4258, USA.

Background: Transcriptome analysis of breast cancer discovered distinct disease subtypes of clinical significance. However, it remains a challenge to define disease biology solely based on gene expression because tumor biology is often the result of protein function. Here, we measured global proteome and transcriptome expression in human breast tumors and adjacent non-cancerous tissue and performed an integrated proteotranscriptomic analysis. Read More

View Article

Download full-text PDF

Source
http://dx.doi.org/10.1186/s13073-018-0602-xDOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6276229PMC
December 2018
2 Reads

Time series analysis of neoadjuvant chemotherapy and bevacizumab-treated breast carcinomas reveals a systemic shift in genomic aberrations.

Genome Med 2018 11 29;10(1):92. Epub 2018 Nov 29.

Department of Genetics, Institute for Cancer Research, Oslo University Hospital Radiumhospitalet, Postboks 4953 Nydalen, 0424, Oslo, Norway.

Background: Chemotherapeutic agents such as anthracyclines and taxanes are commonly used in the neoadjuvant setting. Bevacizumab is an antibody which binds to vascular endothelial growth factor A (VEGFA) and inhibits its receptor interaction, thus obstructing the formation of new blood vessels.

Methods: A phase II randomized clinical trial of 123 patients with Her2-negative breast cancer was conducted, with patients treated with neoadjuvant chemotherapy (fluorouracil (5FU)/epirubicin/cyclophosphamide (FEC) and taxane), with or without bevacizumab. Read More

View Article

Download full-text PDF

Source
http://dx.doi.org/10.1186/s13073-018-0601-yDOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6262977PMC
November 2018
2 Reads

Genomics of response to immune checkpoint therapies for cancer: implications for precision medicine.

Genome Med 2018 11 29;10(1):93. Epub 2018 Nov 29.

Department of Medical Oncology, Dana-Farber Cancer Institute, Boston, MA, 02215, USA.

Immune checkpoint blockade (ICB) therapies, which potentiate the body's natural immune response against tumor cells, have shown immense promise in the treatment of various cancers. Currently, tumor mutational burden (TMB) and programmed death ligand 1 (PD-L1) expression are the primary biomarkers evaluated for clinical management of cancer patients across histologies. However, the wide range of responses has demonstrated that the specific molecular and genetic characteristics of each patient's tumor and immune system must be considered to maximize treatment efficacy. Read More

View Article

Download full-text PDF

Source
http://dx.doi.org/10.1186/s13073-018-0605-7DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6264032PMC
November 2018
2 Reads

Identification of Jun loss promotes resistance to histone deacetylase inhibitor entinostat through Myc signaling in luminal breast cancer.

Genome Med 2018 11 30;10(1):86. Epub 2018 Nov 30.

Lineberger Comprehensive Cancer Center, University of North Carolina at Chapel Hill, Chapel Hill, NC, 27599, USA.

Background: Based on promising phase II data, the histone deacetylase inhibitor entinostat is in phase III trials for patients with metastatic estrogen receptor-positive breast cancer. Predictors of sensitivity and resistance, however, remain unknown.

Methods: A total of eight cell lines and nine mouse models of breast cancer were treated with entinostat. Read More

View Article

Download full-text PDF

Source
https://genomemedicine.biomedcentral.com/articles/10.1186/s1
Publisher Site
http://dx.doi.org/10.1186/s13073-018-0597-3DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6267061PMC
November 2018
17 Reads
4.942 Impact Factor

Inactivation of DNA repair-prospects for boosting cancer immune surveillance.

Genome Med 2018 11 28;10(1):91. Epub 2018 Nov 28.

Candiolo Cancer Institute, FPO-IRCCS, Candiolo, TO, Italy.

The emergence of drug resistance depends on the ability of the genome of cancer cells to constantly mutate and evolve under selective pressures. The generation of new mutations is accelerated when genes involved in DNA repair pathways are altered. Notably, although the emergence of new mutations fosters drug resistance, new variants can nevertheless become novel antigens that promote immune surveillance and even restrict cancer growth. Read More

View Article

Download full-text PDF

Source
http://dx.doi.org/10.1186/s13073-018-0603-9DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6260742PMC
November 2018
1 Read

A role for the unfolded protein response stress sensor ERN1 in regulating the response to MEK inhibitors in KRAS mutant colon cancers.

Genome Med 2018 11 27;10(1):90. Epub 2018 Nov 27.

Division of Molecular Carcinogenesis, Oncode Institute, The Netherlands Cancer Institute, Plesmanlaan 121, Amsterdam, 1066 CX, The Netherlands.

Background: Mutations in KRAS are frequent in human cancer, yet effective targeted therapeutics for these cancers are still lacking. Attempts to drug the MEK kinases downstream of KRAS have had limited success in clinical trials. Understanding the specific genomic vulnerabilities of KRAS-driven cancers may uncover novel patient-tailored treatment options. Read More

View Article

Download full-text PDF

Source
https://genomemedicine.biomedcentral.com/articles/10.1186/s1
Publisher Site
http://dx.doi.org/10.1186/s13073-018-0600-zDOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6258447PMC
November 2018
3 Reads

The ins and outs of telomere crisis in cancer.

Genome Med 2018 11 27;10(1):89. Epub 2018 Nov 27.

Molecular Biology Program, Sloan Kettering Institute, Memorial Sloan Kettering Cancer Center, New York, NY, 10065, USA.

Telomere crisis is linked with many of the genomic alterations found in cancer genomes. A new understanding of how these alterations arise points towards an active role for innate immune sensors during crisis and to new opportunities for the treatment and diagnosis of cancer. Read More

View Article

Download full-text PDF

Source
http://dx.doi.org/10.1186/s13073-018-0596-4DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6258172PMC
November 2018
2 Reads

Early life immunity in the era of systems biology: understanding development and disease.

Genome Med 2018 11 23;10(1):88. Epub 2018 Nov 23.

Institute for Immunity, Transplantation, and Infection, Stanford University School of Medicine, Stanford, CA, 94305, USA.

Systems immunology has the potential to offer invaluable insights into the development of the immune system. Two recent studies offer an in-depth view of both the dynamics of immune system development and the heritability of the levels of key immune modulators at birth. Read More

View Article

Download full-text PDF

Source
https://genomemedicine.biomedcentral.com/articles/10.1186/s1
Publisher Site
http://dx.doi.org/10.1186/s13073-018-0599-1DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6260988PMC
November 2018
2 Reads

Acquired mechanisms of immune escape in cancer following immunotherapy.

Genome Med 2018 11 22;10(1):87. Epub 2018 Nov 22.

Department of Medical Oncology, Dana-Farber Cancer Institute, Boston, MA, 02115, USA.

Immunotherapy has revolutionized the management of numerous cancers; however, a substantial proportion that initially respond subsequently acquire means of immune escape and relapse. Analysis of recent clinical trials permits us to preliminarily understand how immunotherapies exert evolutionary pressures: selecting cancer subclones deficient in antigenicity and/or immunogenicity, thereby facilitating immune escape. Read More

View Article

Download full-text PDF

Source
http://dx.doi.org/10.1186/s13073-018-0598-2DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6249768PMC
November 2018
1 Read

Cell-free DNA profiling of metastatic prostate cancer reveals microsatellite instability, structural rearrangements and clonal hematopoiesis.

Genome Med 2018 11 21;10(1):85. Epub 2018 Nov 21.

Department of Medical Epidemiology and Biostatistics, Science for Life Laboratory, Karolinska Institutet, Stockholm, Sweden.

Background: There are multiple existing and emerging therapeutic avenues for metastatic prostate cancer, with a common denominator, which is the need for predictive biomarkers. Circulating tumor DNA (ctDNA) has the potential to cost-efficiently accelerate precision medicine trials to improve clinical efficacy and diminish costs and toxicity. However, comprehensive ctDNA profiling in metastatic prostate cancer to date has been limited. Read More

View Article

Download full-text PDF

Source
http://dx.doi.org/10.1186/s13073-018-0595-5DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6247769PMC
November 2018
13 Reads

Footprints of antigen processing boost MHC class II natural ligand predictions.

Genome Med 2018 11 16;10(1):84. Epub 2018 Nov 16.

Instituto de Investigaciones Biotecnológicas, Universidad Nacional de San Martín, CP1650, San Martín, Argentina.

Background: Major histocompatibility complex class II (MHC-II) molecules present peptide fragments to T cells for immune recognition. Current predictors for peptide to MHC-II binding are trained on binding affinity data, generated in vitro and therefore lacking information about antigen processing.

Methods: We generate prediction models of peptide to MHC-II binding trained with naturally eluted ligands derived from mass spectrometry in addition to peptide binding affinity data sets. Read More

View Article

Download full-text PDF

Source
https://genomemedicine.biomedcentral.com/articles/10.1186/s1
Publisher Site
http://dx.doi.org/10.1186/s13073-018-0594-6DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6240193PMC
November 2018
15 Reads

Computational analysis reveals histotype-dependent molecular profile and actionable mutation effects across cancers.

Genome Med 2018 11 15;10(1):83. Epub 2018 Nov 15.

Institute of Pathology, Charité - Universitätsmedizin Berlin, corporate member of Freie Universität Berlin, Humboldt-Universität zu Berlin and Berlin Institute of Health, Berlin, Germany.

Background: Comprehensive mutational profiling data now available on all major cancers have led to proposals of novel molecular tumor classifications that modify or replace the established organ- and tissue-based tumor typing. The rationale behind such molecular reclassifications is that genetic alterations underlying cancer pathology predict response to therapy and may therefore offer a more precise view on cancer than histology. The use of individual actionable mutations to select cancers for treatment across histotypes is already being tested in the so-called basket trials with variable success rates. Read More

View Article

Download full-text PDF

Source
http://dx.doi.org/10.1186/s13073-018-0591-9DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6238410PMC
November 2018
2 Reads

Whole-genome epidemiology, characterisation, and phylogenetic reconstruction of Staphylococcus aureus strains in a paediatric hospital.

Genome Med 2018 11 13;10(1):82. Epub 2018 Nov 13.

Centre for Integrative Biology, University of Trento, Trento, Italy.

Background: Staphylococcus aureus is an opportunistic pathogen and a leading cause of nosocomial infections. It can acquire resistance to all the antibiotics that entered the clinics to date, and the World Health Organization defined it as a high-priority pathogen for research and development of new antibiotics. A deeper understanding of the genetic variability of S. Read More

View Article

Download full-text PDF

Source
https://genomemedicine.biomedcentral.com/articles/10.1186/s1
Publisher Site
http://dx.doi.org/10.1186/s13073-018-0593-7DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6234625PMC
November 2018
17 Reads

Landscape of genomic alterations in high-grade serous ovarian cancer from exceptional long- and short-term survivors.

Genome Med 2018 10 31;10(1):81. Epub 2018 Oct 31.

Princess Margaret Cancer Centre, University Health Network, 610 University Avenue, Toronto, Ontario, M5G 2M9, Canada.

Background: Patients diagnosed with high-grade serous ovarian cancer (HGSOC) who received initial debulking surgery followed by platinum-based chemotherapy can experience highly variable clinical responses. A small percentage of women experience exceptional long-term survival (long term (LT), 10+ years), while others develop primary resistance to therapy and succumb to disease in less than 2 years (short term (ST)). To improve clinical management of HGSOC, there is a need to better characterize clinical and molecular profiles to identify factors that underpin these disparate survival responses. Read More

View Article

Download full-text PDF

Source
http://dx.doi.org/10.1186/s13073-018-0590-xDOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6208125PMC
October 2018
15 Reads
4.942 Impact Factor

Distinct microbes, metabolites, and ecologies define the microbiome in deficient and proficient mismatch repair colorectal cancers.

Genome Med 2018 10 31;10(1):78. Epub 2018 Oct 31.

Microbiome Program, Center for Individualized Medicine, Mayo Clinic, Rochester, MN, USA.

Background: Links between colorectal cancer (CRC) and the gut microbiome have been established, but the specific microbial species and their role in carcinogenesis remain an active area of inquiry. Our understanding would be enhanced by better accounting for tumor subtype, microbial community interactions, metabolism, and ecology.

Methods: We collected paired colon tumor and normal-adjacent tissue and mucosa samples from 83 individuals who underwent partial or total colectomies for CRC. Read More

View Article

Download full-text PDF

Source
https://genomemedicine.biomedcentral.com/articles/10.1186/s1
Publisher Site
http://dx.doi.org/10.1186/s13073-018-0586-6DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6208080PMC
October 2018
6 Reads

Targeting the microbiome: from probiotics to fecal microbiota transplantation.

Genome Med 2018 10 30;10(1):80. Epub 2018 Oct 30.

Department of Medicine, Division of Gastroenterology, Hepatology, and Nutrition, Center for Immunology, and BioTechnology Institute, University of Minnesota, Wallin Medical Biosciences Building, 2101 6th Street South East, Room 3-184, Minneapolis, MN, 55414, USA.

The modern techniques of microbiome science can be applied to the development and evaluation of all microbiota-directed products, including probiotics and fecal microbiota transplantation. Read More

View Article

Download full-text PDF

Source
https://genomemedicine.biomedcentral.com/articles/10.1186/s1
Publisher Site
http://dx.doi.org/10.1186/s13073-018-0592-8DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6208019PMC
October 2018
4 Reads

Recent advances in immunotherapies: from infection and autoimmunity, to cancer, and back again.

Genome Med 2018 10 31;10(1):79. Epub 2018 Oct 31.

Parker Institute of Cancer Immunotherapy, 1 Letterman Drive, San Francisco, CA, USA.

For at least 300 years the immune system has been targeted to improve human health. Decades of work advancing immunotherapies against infection and autoimmunity paved the way for the current explosion in cancer immunotherapies. Pathways targeted for therapeutic intervention in autoimmune diseases can be modulated in the opposite sense in malignancy and infectious disease. Read More

View Article

Download full-text PDF

Source
https://genomemedicine.biomedcentral.com/articles/10.1186/s1
Publisher Site
http://dx.doi.org/10.1186/s13073-018-0588-4DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6208073PMC
October 2018
23 Reads

Tracking key virulence loci encoding aerobactin and salmochelin siderophore synthesis in Klebsiella pneumoniae.

Genome Med 2018 10 29;10(1):77. Epub 2018 Oct 29.

Department of Biochemistry and Molecular Biology, Bio21 Molecular Science and Biotechnology Institute, University of Melbourne, Parkville, Victoria, 3010, Australia.

Background: Klebsiella pneumoniae is a recognised agent of multidrug-resistant (MDR) healthcare-associated infections; however, individual strains vary in their virulence potential due to the presence of mobile accessory genes. In particular, gene clusters encoding the biosynthesis of siderophores aerobactin (iuc) and salmochelin (iro) are associated with invasive disease and are common amongst hypervirulent K. pneumoniae clones that cause severe community-associated infections such as liver abscess and pneumonia. Read More

View Article

Download full-text PDF

Source
https://genomemedicine.biomedcentral.com/articles/10.1186/s1
Publisher Site
http://dx.doi.org/10.1186/s13073-018-0587-5DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6205773PMC
October 2018
22 Reads