RT Journal Article
T1 Systematic identification of phenotypically enriched loci using a patient network of genomic disorders.
A1 Reyes-Palomares, Armando
A1 Bueno, Anibal
A1 Rodriguez-Lopez, Rocio
A1 Medina, Miguel Angel
A1 Sanchez-Jimenez, Francisca
A1 Corpas, Manuel
A1 Ranea, Juan A G
K1 Databases, genetic
K1 Genetic Loci
K1 Phenotype
AB Network medicine is a promising new discipline that combines systems biology approaches and network science to understand the complexity of pathological phenotypes. Given the growing availability of personalized genomic and phenotypic profiles, network models offer a robust integrative framework for the analysis of "omics" data, allowing the characterization of the molecular aetiology of pathological processes underpinning genetic diseases. Here we make use of patient genomic data to exploit different network-based analyses to study genetic and phenotypic relationships between individuals. For this method, we analyzed a dataset of structural variants and phenotypes for 6,564 patients from the DECIPHER database, which encompasses one of the most comprehensive collections of pathogenic Copy Number Variations (CNVs) and their associated ontology-controlled phenotypes. We developed a computational strategy that identifies clusters of patients in a synthetic patient network according to their genetic overlap and phenotype enrichments. Many of these clusters of patients represent new genotype-phenotype associations, suggesting the identification of newly discovered phenotypically enriched loci (indicative of potential novel syndromes) that are currently absent from reference genomic disorder databases such as ClinVar, OMIM or DECIPHER itself. We provide a high-resolution map of pathogenic phenotypes associated with their respective significant genomic regions and a new powerful tool for diagnosis of currently uncharacterized mutations leading to deleterious phenotypes and syndromes.
PB Springer Nature
YR 2016
FD 2016-03-07
LK http://hdl.handle.net/10668/9920
UL http://hdl.handle.net/10668/9920
LA en
NO Reyes-Palomares A, Bueno A, Rodríguez-López R, Medina MÁ, Sánchez-Jiménez F, Corpas M, et al. Systematic identification of phenotypically enriched loci using a patient network of genomic disorders. BMC Genomics. 2016 Mar 15;17:232
NO This work was funded by CIBERER (U741), EU-FP7-Systems Microscopy NoE (Grant Agreement 258068), and grants SAF2011-26518, SAF2012-33110 (MEC, Spain), BIO2014-56092-R (MINECO and FEDER, Spain), and CTS-486, CTS-1507 and CVI-06585 Excellence Grants (Junta de Andalucía, Spain), and BIO-267 (fondos PAIDI, Junta de Andalucía, Spain). MC is grateful to UK’s BBSRC for core funding. The “CIBER de Enfermedades Raras” is an initiative from the ISCIII (Spain). The funders had no role in the study design, data collection and analysis, decision to publish or preparation of the manuscript. ARP is recipient of a postdoctoral fellowship granted by Fundación Ramón Areces. This study makes use of data generated by the DECIPHER community. A full list of centres who contributed to the generation of the data is available from http://decipher.sanger.ac.uk and via email from decipher@sanger.ac.uk. Funding for the project was provided by the Wellcome Trust.
DS RISalud
RD Apr 11, 2025