Abstract:
BACKGROUND:One of the major goals of genomic medicine is the identification of causal genomic variants in a patient and their relation to the observed clinical phenotypes. Prioritizing the genomic variants by considering only the genotype information usually identifies a few hundred potential variants. Narrowing it down further to find the causal disease genes and relating them to the observed clinical phenotypes remains a significant challenge, especially for rare diseases. METHODS:We propose a phenotype-driven gene prioritization approach using heterogeneous networks in the context of rare diseases. Towards this, we first built a heterogeneous network consisting of ontological associations as well as curated associations involving genes, diseases, phenotypes and pathways from multiple sources. Motivated by the recent progress in spectral graph convolutions, we developed a graph convolution based technique to infer new phenotype-gene associations from this initial set of associations. We included these inferred associations in the initial network and termed this integrated network HANRD (Heterogeneous Association Network for Rare Diseases). We validated this approach on 230 recently published rare disease clinical cases using the case phenotypes as input. RESULTS:When HANRD was queried with the case phenotypes as input, the causal genes were captured within Top-50 for more than 31% of the cases and within Top-200 for more than 56% of the cases. The results showed improved performance when compared to other state-of-the-art tools. CONCLUSIONS:In this study, we showed that the heterogeneous network HANRD, consisting of curated, ontological and inferred associations, helped improve causal gene identification in rare diseases. HANRD allows future enhancements by supporting incorporation of new entity types and additional information sources.
journal_name
BMC Med Genomicsjournal_title
BMC medical genomicsauthors
Rao A,Vg S,Joseph T,Kotte S,Sivadasan N,Srinivasan Rdoi
10.1186/s12920-018-0372-8subject
Has Abstractpub_date
2018-07-06 00:00:00pages
57issue
1issn
1755-8794pii
10.1186/s12920-018-0372-8journal_volume
11pub_type
杂志文章abstract:BACKGROUND:Recent advances in whole-genome association studies (WGASs) for human cancer risk are beginning to provide the part lists of low-penetrance susceptibility genes. However, statistical analysis in these studies is complicated by the vast number of genetic variants examined and the weak effects observed, as a r...
journal_title:BMC medical genomics
pub_type: 杂志文章
doi:10.1186/1755-8794-1-62
更新日期:2008-12-18 00:00:00
abstract:BACKGROUND:Bladder cancer has numerous genomic features that are potentially actionable by targeted agents. Nevertheless, both pre-clinical and clinical research using molecular targeted agents have been very limited in bladder cancer. RESULTS:We created the Genomics of Drug Sensitivity in Bladder Cancer (GDBC) databa...
journal_title:BMC medical genomics
pub_type: 杂志文章
doi:10.1186/s12920-018-0406-2
更新日期:2018-10-03 00:00:00
abstract:BACKGROUND:Glioblastoma is a complex multifactorial disorder that has swift and devastating consequences. Few genes have been consistently identified as prognostic biomarkers of glioblastoma survival. The goal of this study was to identify general and clinical-dependent biomarker genes and biological processes of three...
journal_title:BMC medical genomics
pub_type: 杂志文章
doi:10.1186/1755-8794-4-49
更新日期:2011-06-07 00:00:00
abstract:BACKGROUND:Birt-Hogg-Dubé syndrome (BHD) is an autosomal dominant disorder caused by germline mutations in the folliculin gene (FLCN). Nearly 150 pathogenic mutations have been identified in FLCN. The most frequent pattern is a frameshift mutation within a coding exon. In addition, splice-site mutations have been repor...
journal_title:BMC medical genomics
pub_type: 杂志文章
doi:10.1186/s12920-018-0359-5
更新日期:2018-05-02 00:00:00
abstract:BACKGROUND:A clinical overlap exists between mosaic Neurofibromatosis Type 2 and sporadic Schwannomatosis conditions. In these cases a molecular analysis of tumors is recommended for a proper genetic diagnostics. This analysis is challenged by the fact that schwannomas in both conditions bear a somatic double inactivat...
journal_title:BMC medical genomics
pub_type: 杂志文章
doi:10.1186/s12920-015-0076-2
更新日期:2015-01-24 00:00:00
abstract:BACKGROUND:Breast cancer comprises multiple tumor entities associated with different biological features and clinical behaviors, making individualized medicine a powerful tool to bring the right drug to the right patient. Next generation sequencing of RNA (RNA-Seq) is a suitable method to detect targets for individuali...
journal_title:BMC medical genomics
pub_type: 杂志文章
doi:10.1186/s12920-015-0095-z
更新日期:2015-05-21 00:00:00
abstract:BACKGROUND:Rapid advances in scientific research have led to an increase in public awareness of genetic testing and pharmacogenetics. Direct-to-consumer (DTC) genetic testing companies, such as 23andMe, allow consumers to access their genetic information directly through an online service without the involvement of hea...
journal_title:BMC medical genomics
pub_type: 杂志文章
doi:10.1186/s12920-017-0283-0
更新日期:2017-06-19 00:00:00
abstract:BACKGROUND:Aberrant epigenetic profiles are concomitant with a spectrum of developmental defects and diseases. Role of methylation is an increasingly accepted factor in the pathophysiology of diabetes and its associated complications. This study aims to examine the correlation between oxidative stress and methylation o...
journal_title:BMC medical genomics
pub_type: 杂志文章
doi:10.1186/1755-8794-7-29
更新日期:2014-05-30 00:00:00
abstract:BACKGROUND:DNA methylation levels will be important for detection of epigenetic effects. However, there are few reports showing sex-related differences in the sensitivity to DNA methylation. To evaluate their sex-related individual differences in the sensitivity to methylation rigorously, we performed a systematic anal...
journal_title:BMC medical genomics
pub_type: 杂志文章
doi:10.1186/s12920-016-0217-2
更新日期:2016-08-26 00:00:00
abstract:BACKGROUND:Diabetic retinopathy (DR) is a leading cause of blindness in working age adults. Approximately 95% of patients with Type 1 diabetes develop some degree of retinopathy within 25 years of diagnosis despite normalization of blood glucose by insulin therapy. The goal of this study was to identify molecular chang...
journal_title:BMC medical genomics
pub_type: 杂志文章
doi:10.1186/1755-8794-4-40
更新日期:2011-05-15 00:00:00
abstract:BACKGROUND:Childhood asthma is a syndrome composed of heterogeneous phenotypes; furthermore, intrinsic biologic variation among racial/ethnic populations suggests possible genetic ancestry variation in childhood asthma. The objective of the study is to identify clinically homogeneous asthma subphenotypes in a diverse s...
journal_title:BMC medical genomics
pub_type: 杂志文章
doi:10.1186/s12920-018-0367-5
更新日期:2018-05-31 00:00:00
abstract:BACKGROUND:The increasing trend for incorporation of biological sample collection within clinical trials requires sample collection procedures which are convenient and acceptable for both patients and clinicians. This study investigated the feasibility of using saliva-extracted DNA in comparison to blood-derived DNA, a...
journal_title:BMC medical genomics
pub_type: 杂志文章
doi:10.1186/1755-8794-5-19
更新日期:2012-05-30 00:00:00
abstract:BACKGROUND:Small non-coding regulatory RNAs control cellular functions at the transcriptional and post-transcriptional levels. Oral squamous cell carcinoma is among the leading cancers in the world and the presence of cervical lymph node metastases is currently its strongest prognostic factor. In this work we aimed at ...
journal_title:BMC medical genomics
pub_type: 杂志文章
doi:10.1186/s12920-015-0102-4
更新日期:2015-06-24 00:00:00
abstract:BACKGROUND:Uric acid is the primary byproduct of purine metabolism. Hyperuricemia is associated with body mass index (BMI), sex, and multiple complex diseases including gout, hypertension (HTN), renal disease, and type 2 diabetes (T2D). Multiple genome-wide association studies (GWAS) in individuals of European ancestry...
journal_title:BMC medical genomics
pub_type: 杂志文章
doi:10.1186/1755-8794-4-17
更新日期:2011-02-04 00:00:00
abstract:BACKGROUND:The growing advances in DNA sequencing tools have made analyzing the human genome cheaper and faster. While such analyses are intended to identify complex variants, related to disease susceptibility and efficacy of drug responses, they have blurred the definitions of mutation and polymorphism. DISCUSSION:In...
journal_title:BMC medical genomics
pub_type: 杂志文章
doi:10.1186/s12920-015-0115-z
更新日期:2015-07-15 00:00:00
abstract:BACKGROUND:While BMPR2 mutation strongly predisposes to pulmonary arterial hypertension (PAH), only 20% of mutation carriers develop clinical disease. This finding suggests that modifier genes contribute to FPAH clinical expression. Since modifiers are likely to be common alleles, this problem is not tractable by tradi...
journal_title:BMC medical genomics
pub_type: 杂志文章
doi:10.1186/1755-8794-1-45
更新日期:2008-09-29 00:00:00
abstract:BACKGROUND:Cancer cells are characterized by massive dysegulation of physiological cell functions with considerable disruption of transcriptional regulation. Genome-wide transcriptome profiling can be utilized for early detection and molecular classification of cancers. Accurate discrimination of functionally different...
journal_title:BMC medical genomics
pub_type: 杂志文章
doi:10.1186/1755-8794-4-53
更新日期:2011-06-30 00:00:00
abstract:BACKGROUND:Fat mass and obesity-associated (FTO) gene has been under close investigation since the discovery of its high impact on the obesity status in 2007 by a range of publications. Recent report on its implication in adipocytes underscored its molecular and functional mechanics in pathology. Still, the population ...
journal_title:BMC medical genomics
pub_type: 杂志文章
doi:10.1186/s12920-019-0491-x
更新日期:2019-03-13 00:00:00
abstract:BACKGROUND:To explore long-non-coding RNA (lncRNA), microRNA (miRNA) and messenger RNA (mRNA) expression profiles and their biological functions in the urine samples in calcium oxalate (CaOx) patients. METHODS:Five CaOx kidney stone patients were recruited in CaOx stone group and six healthy people were included as co...
journal_title:BMC medical genomics
pub_type: 杂志文章
doi:10.1186/s12920-019-0502-y
更新日期:2019-04-29 00:00:00
abstract::Sickle cell disease and β thalassemia are common severe diseases with little effective pathophysiologically-based treatment. Their phenotypic heterogeneity prompted genomic approaches to identify modifiers that ultimately might be exploited therapeutically. Fetal hemoglobin (HbF) is the major modulator of the phenotyp...
journal_title:BMC medical genomics
pub_type: 杂志文章,评审
doi:10.1186/s12920-015-0120-2
更新日期:2015-07-29 00:00:00
abstract:BACKGROUND:Testing strategies is crucial for genetics clinics and testing laboratories. In this study, we tried to compare the hit rate between solo and trio and trio plus testing and between trio and sibship testing. Finally, we studied the impact of extended family analysis, mainly in complex and unsolved cases. MET...
journal_title:BMC medical genomics
pub_type: 杂志文章
doi:10.1186/s12920-020-00743-8
更新日期:2020-07-17 00:00:00
abstract:BACKGROUND:A plethora of cases are reported in the literature with iso- and ring-chromosome 18. However, co-occurrence of these two abnormalities in an individual along with a third cell line and absence of numerical anomaly is extremely rare. CASE PRESENTATION:A 7-year-old female was referred for diagnosis due to gro...
journal_title:BMC medical genomics
pub_type: 杂志文章
doi:10.1186/s12920-020-00796-9
更新日期:2020-09-24 00:00:00
abstract:BACKGROUND:Systemic sclerosis (SSc), a multi-organ disorder, is characterized by vascular abnormalities, dysregulation of the immune system, and fibrosis. The mechanisms underlying tissue pathology in SSc have not been entirely understood. This study intended to investigate the common and tissue-specific pathways invol...
journal_title:BMC medical genomics
pub_type: 杂志文章
doi:10.1186/s12920-019-0632-2
更新日期:2019-12-27 00:00:00
abstract:BACKGROUND:Germline mutations in the folliculin (FLCN) gene are associated with the development of Birt-Hogg-Dubé syndrome (BHDS), a disease characterized by papular skin lesions, a high occurrence of spontaneous pneumothorax, and the development of renal neoplasias. The majority of renal tumors that arise in BHDS-affe...
journal_title:BMC medical genomics
pub_type: 杂志文章
doi:10.1186/1755-8794-3-59
更新日期:2010-12-16 00:00:00
abstract:BACKGROUND:Primary microcephaly represents an example of clinically and genetically heterogeneous condition. Here we describe a case of primary microcephaly from the Karachay-Cherkess Republic, which was initially diagnosed with Seckel syndrome. CASE PRESENTATION:Clinical exome sequencing of the proband revealed a nov...
journal_title:BMC medical genomics
pub_type: 杂志文章
doi:10.1186/s12920-018-0326-1
更新日期:2018-02-13 00:00:00
abstract:BACKGROUND:Prognostic signatures are vital to precision medicine. However, development of somatic mutation prognostic signatures for cancers remains a challenge. In this study we developed a novel method for discovering somatic mutation based prognostic signatures. RESULTS:Somatic mutation and clinical data for lung a...
journal_title:BMC medical genomics
pub_type: 杂志文章
doi:10.1186/s12920-018-0454-7
更新日期:2019-01-31 00:00:00
abstract:BACKGROUND:To get insight into molecular mechanisms underlying insulin resistance, we compared acute in vivo effects of insulin on adipose tissue transcriptional profiles between obese insulin-resistant and lean insulin-sensitive women. METHODS:Subcutaneous adipose tissue biopsies were obtained before and after 3 and ...
journal_title:BMC medical genomics
pub_type: 杂志文章
doi:10.1186/1755-8794-5-9
更新日期:2012-04-03 00:00:00
abstract:BACKGROUND:As the sixth most common cancer worldwide, head and neck squamous cell carcinoma (HNSCC) develops visceral metastases during the advanced stage of the disease and exhibits a low five-year survival rate. The importance of tumor microenvironment (TME) in tumor initiation and metastasis is widely recognized. In...
journal_title:BMC medical genomics
pub_type: 杂志文章
doi:10.1186/s12920-020-0707-0
更新日期:2020-03-30 00:00:00
abstract:BACKGROUND:The majority of copy number callers requires high read coverage data that is often achieved with elevated material input, which increases the heterogeneity of tissue samples. However, to gain insights into smaller areas within a tissue sample, e.g. a cancerous area in a heterogeneous tissue sample, less mate...
journal_title:BMC medical genomics
pub_type: 杂志文章
doi:10.1186/s12920-020-00731-y
更新日期:2020-06-01 00:00:00
abstract:BACKGROUND:The right dataset is essential to obtain the right insights in data science; therefore, it is important for data scientists to have a good understanding of the availability of relevant datasets as well as the content, structure, and existing analyses of these datasets. While a number of efforts are underway ...
journal_title:BMC medical genomics
pub_type: 杂志文章
doi:10.1186/s12920-018-0411-5
更新日期:2018-11-20 00:00:00