BMC Medical Genomics

https://bmcmedgenomics.biomedcentral.com

List of Papers (Total 871)

Transient multifocal genomic crisis creating chromothriptic and non-chromothriptic rearrangements in prezygotic testicular germ cells

The co-occurrence of multiple de novo copy number variations (CNVs) is a rare phenomenon in the human genome. Recently, an “organismal CNV mutator phenotype” has been reported to result in transient genomic instability introducing multiple de novo CNVs in primary oocytes and early-stage zygotes. These findings opened a new area of human genome research. We performed genome-wide...

Histamine H4 receptor gene polymorphisms: a potential contributor to Meniere disease

The immune system is likely involved in the pathophysiology of Meniere’s disease (MD). However, its role of patients with MD has not been well studied. Given that histamine H4 receptors are highly expressed in immune system, we tested the hypothesis that histamine H4 receptor gene polymorphisms are a potential contributor to the risk of MD. A group of patients was enrolled with a...

Exome-wide search and functional annotation of genes associated in patients with severe tick-borne encephalitis in a Russian population

Tick-borne encephalitis (TBE) is a viral infectious disease caused by tick-borne encephalitis virus (TBEV). TBEV infection is responsible for a variety of clinical manifestations ranging from mild fever to severe neurological illness. Genetic factors involved in the host response to TBEV that may potentially play a role in the severity of the disease are still poorly understood...

Exploiting orthology and de novo transcriptome assembly to refine target sequence information

The ability to generate recombinant drug target proteins is important for drug discovery research as it facilitates the investigation of drug-target-interactions in vitro. To accomplish this, the target’s exact protein sequence is required. Public databases, such as Ensembl, UniProt and RefSeq, are extensive protein and nucleotide sequence repositories. However, many sequences...

Identification of potential biomarkers for diagnosis of pancreatic and biliary tract cancers by sequencing of serum microRNAs

Pancreatic and biliary tract cancer (PC and BTC, respectively) are difficult to diagnose because of their clinical characteristics; however, recent studies suggest that serum microRNAs (miRNAs) might be the key to developing more efficient diagnostic methods for these cancers. We analysed the genome-wide expression of serum miRNAs in PC and BTC patients to identify novel...

NeoMutate: an ensemble machine learning framework for the prediction of somatic mutations in cancer

The accurate screening of tumor genomic landscapes for somatic mutations using high-throughput sequencing involves a crucial step in precise clinical diagnosis and targeted therapy. However, the complex inherent features of cancer tissue, especially, tumor genetic intra-heterogeneity coupled with the problem of sequencing and alignment artifacts, makes somatic variant calling a...

Familial inheritance of the 3q29 microdeletion syndrome: case report and review

The chromosome 3q29 microdeletion syndrome is characterized by a clinical phenotype that includes behavioral features consistent with autism and attention deficit hyperactivity disorder, mild to moderate developmental delay, language-based learning disabilities, and/or dysmorphic features. In addition, recent data suggest that adults with chromosome 3q29 microdeletions have a...

Exome, transcriptome and miRNA analysis don’t reveal any molecular markers of TKI efficacy in primary CML patients

Approximately 5–20% of chronic myeloid leukemia (CML) patients demonstrate primary resistance or intolerance to imatinib. None of the existing predictive scores gives a good prognosis of TKI efficacy. Gene polymorphisms, expression and microRNAs are known to be involved in the pathogenesis of TKI resistance in CML. The aim of our study is to find new molecular markers of TKI...

Interrelation of chemerin and TNF-α with mtDNA copy number in adipose tissues and blood cells in obese patients with and without type 2 diabetes

Inflammatory response plays a key role in the development of insulin resistance (IR) in obesity. Oxidative stress triggers the replication of the mitochondrial genome and division of the organelle. The purpose of this study was to identify the relationship of chemerin and TNF-α with mitochondrial DNA (mtDNA) copy number in subcutaneous adipose tissue (SAT) and visceral adipose...

Design and analysis of stably integrated reporters for inducible transgene expression in human T cells and CAR NK-cell lines

Cytotoxic activity of T- and NK-cells can be efficiently retargeted against cancer cells using chimeric antigen receptors (CARs) and rTCRs. In the context of solid cancers, use of armored CAR T- and NK cells secreting additional anti-cancer molecules such as cytokines, chemokines, antibodies, BiTEs, inverted cytokine receptors, and checkpoint inhibitors, appears particularly...

Early gut microbiota signature of aGvHD in children given allogeneic hematopoietic cell transplantation for hematological disorders

The onset of acute Graft-versus-Host Disease (aGvHD) has been correlated with the gut microbiota (GM) composition, but experimental observations are still few, mainly involving cohorts of adult patients. In the current scenario where fecal microbiota transplantation has been used as a pioneer therapeutic approach to treat steroid-refractory aGvHD, there is an urgent need to...

Complex structural rearrangements are present in high-grade dysplastic Barrett’s oesophagus samples

Oesophageal adenocarcinoma (EAC) incidence is increasing and has a poor survival rate. Barrett’s oesophagus (BE) is a precursor condition that is associated with EAC and often occurs in conjunction with chronic gastro-oesophageal reflux, however many individuals diagnosed with BE never progress to cancer. An understanding of the genomic features of BE and EAC may help with the...

Chromosome (re)positioning in spermatozoa of fathers and sons – carriers of reciprocal chromosome translocation (RCT)

Non-random chromosome positioning has been observed in the nuclei of several different tissue types, including human spermatozoa. The nuclear arrangement of chromosomes can be altered in men with decreased semen parameters or increased DNA fragmentation and in males with chromosomal numerical or structural aberrations. An aim of this study was to determine whether and how the...

Predict drug sensitivity of cancer cells with pathway activity inference

Predicting cellular responses to drugs has been a major challenge for personalized drug therapy regimen. Recent pharmacogenomic studies measured the sensitivities of heterogeneous cell lines to numerous drugs, and provided valuable data resources to develop and validate computational approaches for the prediction of drug responses. Most of current approaches predict drug...

Novel disease syndromes unveiled by integrative multiscale network analysis of diseases sharing molecular effectors and comorbidities

Forty-two percent of patients experience disease comorbidity, contributing substantially to mortality rates and increased healthcare costs. Yet, the possibility of underlying shared mechanisms for diseases remains not well established, and few studies have confirmed their molecular predictions with clinical datasets. In this work, we integrated genome-wide association study (GWAS...

Condition-specific gene co-expression network mining identifies key pathways and regulators in the brain tissue of Alzheimer’s disease patients

Gene co-expression network (GCN) mining is a systematic approach to efficiently identify novel disease pathways, predict novel gene functions and search for potential disease biomarkers. However, few studies have systematically identified GCNs in multiple brain transcriptomic data of Alzheimer’s disease (AD) patients and looked for their specific functions. In this study, we...

Mapping the landscape of tandem repeat variability by targeted long read single molecule sequencing in familial X-linked intellectual disability

The etiology of more than half of all patients with X-linked intellectual disability remains elusive, despite array-based comparative genomic hybridization, whole exome or genome sequencing. Since short read massive parallel sequencing approaches do not allow the detection of larger tandem repeat expansions, we hypothesized that such expansions could be a hidden cause of X-linked...

Genomic analyses based on pulmonary adenocarcinoma in situ reveal early lung cancer signature

Non-small cell lung cancer (NSCLC) represents more than about 80% of the lung cancer. The early stages of NSCLC can be treated with complete resection with a good prognosis. However, most cases are detected at late stage of the disease. The average survival rate of the patients with invasive lung cancer is only about 4%. Adenocarcinoma in situ (AIS) is an intermediate subtype of...

Logistic regression over encrypted data from fully homomorphic encryption

One of the tasks in the 2017 iDASH secure genome analysis competition was to enable training of logistic regression models over encrypted genomic data. More precisely, given a list of approximately 1500 patient records, each with 18 binary features containing information on specific mutations, the idea was for the data holder to encrypt the records using homomorphic encryption...

Pathway networks generated from human disease phenome

Understanding the effect of human genetic variations on disease can provide insight into phenotype-genotype relationships, and has great potential for improving the effectiveness of personalized medicine. While some genetic markers linked to disease susceptibility have been identified, a large number are still unknown. In this paper, we propose a pathway-based approach to extend...

Concurrent somatic KRAS mutation and germline 10q22.3-q23.2 deletion in a patient with juvenile myelomonocytic leukemia, developmental delay, and multiple malformations: a case report

The proto-oncogene KRAS performs an essential function in normal tissue signaling, and the mutation of KRAS gene is a key step in the development of many cancers. Somatic KRAS mutations are often detected in patients with solid and non-solid tumors, whereas germline KRAS mutations are implicated in patients with the Noonan syndrome, cardio-facio-cutaneous (CFC) syndrome and...

Calculating the statistical significance of rare variants causal for Mendelian and complex disorders

With the expanding use of next-gen sequencing (NGS) to diagnose the thousands of rare Mendelian genetic diseases, it is critical to be able to interpret individual DNA variation. To calculate the significance of finding a rare protein-altering variant in a given gene, one must know the frequency of seeing a variant in the general population that is at least as damaging as the...

Genome-wide association study identifies two loci influencing plasma neurofilament light levels

Plasma neurofilament light (NFL) is a promising biomarker for Alzheimer disease (AD), which increases in the early stage of AD and is associated with the progression of AD. We performed a genome-wide association study (GWAS) of plasma NFL in Alzheimer’s Disease Neuroimaging Initiative 1 (ADNI-1) cohort to identify novel variants associated with AD. This study included 179...

Cumulative prognostic power of laminin genes in colorectal cancer

Laminins are a major family of extracellular matrix proteins and the main component of basement membranes. Laminins are involved in many if not all stages of cancer progression, and expression of laminin genes has prognostic value in various types of cancer, including colorectal. Only single laminin genes or components of a single laminin trimer with significant differential...

Targeted sequencing reveals complex, phenotype-correlated genotypes in cystic fibrosis

Cystic fibrosis (CF) is one of the most common life-threatening genetic disorders. Around 2000 variants in the CFTR gene have been identified, with some proportion known to be pathogenic and 300 disease-causing mutations have been characterized in detail by CFTR2 database, which complicates its analysis with conventional methods. We conducted next-generation sequencing (NGS) in a...