Interactive Exploration, Analysis, and Visualization of Complex Phenome-Genome Datasets with ASPIREdb

Tan, Powell Patrick Cheng; Rogić, Sanja; Zoubarev, Anton; McDonald, Cameron; Lui, Frances; Charathsandran, Gayathiri; Jacobson, Matthew P.; Belmadani, Manuel; Leong, Justin; Rossum, Thea Van; Portales-Casamar, Élodie; Qiao, Ying; Calli, Kristina; Li, Xudong; Hudson, Melissa; Rajcan‐Separovic, Evica; Sm, Lewis; Pavlidis, Paul

doi:10.1002/humu.23011

Cited by 3 publications

(2 citation statements)

References 33 publications

(35 reference statements)

Supporting

Mentioning

Contrasting

Order By: Relevance

“…Similarly, we queried the MSSNG database of ASD WGS data (https://research.mss.ng) for de novo damaging variants using the same criteria and annotated our cohort variants with these per‐gene variant counts. These data were loaded into ASPIREdb, our web‐based interactive tool for analysis of genome/phenome datasets, to explore and evaluate candidate variants alongside proband phenotypes.…”

Section: Methodsmentioning

confidence: 99%

See 1 more Smart Citation

Whole genome sequencing and variant discovery in the ASPIRE autism spectrum disorder cohort

et al. 2019

Self Cite

View full text Add to dashboard Cite

Autism spectrum disorder (ASD) is a highly heterogeneous genetic disorder with strong evidence of ASD‐association currently available only for a small number of genes. This makes it challenging to identify the underlying genetic cause in many cases of ASD, and there is a continuing need for further discovery efforts. We sequenced whole genomes of 119 deeply phenotyped ASD probands in order to identify likely pathogenic variants. We prioritized variants found in each subject by predicted damage, population frequency, literature evidence, and phenotype concordance. We used Sanger sequencing to determine the inheritance status of high‐priority variants where possible. We report five novel de novo damaging variants as well as several likely damaging variants of unknown inheritance; these include two novel de novo variants in the well‐established ASD gene SCN2A. The availability of rich phenotypic information and its concordance with the literature allowed us to increase our confidence in pathogenicity of discovered variants, especially in probands without parental DNA. Our results contribute to the documentation of potential pathogenic variants and their associated phenotypes in individuals with ASD.

show abstract

Section: Methodsmentioning

confidence: 99%

“…These data were loaded into ASPIREdb, 24 our web-based interactive tool for analysis of genome/phenome datasets, to explore and evaluate candidate variants alongside proband phenotypes.…”

Section: Variant Filtering and Prioritizationmentioning

confidence: 99%

Whole genome sequencing and variant discovery in the ASPIRE autism spectrum disorder cohort

et al. 2019

Self Cite

View full text Add to dashboard Cite

show abstract

PathOS: a decision support system for reporting high throughput sequencing of cancers in clinical diagnostic laboratories

et al. 2017

View full text Add to dashboard Cite

BackgroundThe increasing affordability of DNA sequencing has allowed it to be widely deployed in pathology laboratories. However, this has exposed many issues with the analysis and reporting of variants for clinical diagnostic use. Implementing a high-throughput sequencing (NGS) clinical reporting system requires a diverse combination of capabilities, statistical methods to identify variants, global variant databases, a validated bioinformatics pipeline, an auditable laboratory workflow, reproducible clinical assays and quality control monitoring throughout. These capabilities must be packaged in software that integrates the disparate components into a useable system.ResultsTo meet these needs, we developed a web-based application, PathOS, which takes variant data from a patient sample through to a clinical report. PathOS has been used operationally in the Peter MacCallum Cancer Centre for two years for the analysis, curation and reporting of genetic tests for cancer patients, as well as the curation of large-scale research studies. PathOS has also been deployed in cloud environments allowing multiple institutions to use separate, secure and customisable instances of the system. Increasingly, the bottleneck of variant curation is limiting the adoption of clinical sequencing for molecular diagnostics. PathOS is focused on providing clinical variant curators and pathology laboratories with a decision support system needed for personalised medicine. While the genesis of PathOS has been within cancer molecular diagnostics, the system is applicable to NGS clinical reporting generally.ConclusionsThe widespread availability of genomic sequencers has highlighted the limited availability of software to support clinical decision-making in molecular pathology. PathOS is a system that has been developed and refined in a hospital laboratory context to meet the needs of clinical diagnostics. The software is available as a set of Docker images and source code at https://github.com/PapenfussLab/PathOS.Electronic supplementary materialThe online version of this article (doi:10.1186/s13073-017-0427-z) contains supplementary material, which is available to authorized users.

show abstract

An analysis of genetic variants associated with autism spectrum disorder

Callaghan¹

2018

View full text Add to dashboard Cite

Interactive Exploration, Analysis, and Visualization of Complex Phenome-Genome Datasets with ASPIREdb

Cited by 3 publications

References 33 publications

Whole genome sequencing and variant discovery in the ASPIRE autism spectrum disorder cohort

Whole genome sequencing and variant discovery in the ASPIRE autism spectrum disorder cohort

PathOS: a decision support system for reporting high throughput sequencing of cancers in clinical diagnostic laboratories

An analysis of genetic variants associated with autism spectrum disorder

Contact Info

Product

Resources

About