title: WHATIF: An open-source desktop application for extraction and management of the incidental findings from next-generation sequencing variant data.
abstract: BACKGROUND
  Identification and evaluation of incidental findings in patients following whole exome (WGS) or whole genome sequencing (WGS) is challenging for both practicing physicians and researchers. The American College of Medical Genetics and Genomics (ACMG) recently recommended a list of reportable incidental genetic findings. However, no informatics tools are currently available to support evaluation of incidental findings in next-generation sequencing data.
  
  
  METHODS
  The Wisconsin Hierarchical Analysis Tool for Incidental Findings (WHATIF), was developed as a stand-alone Windows-based desktop executable, to support the interactive analysis of incidental findings in the context of the ACMG recommendations. WHATIF integrates the European Bioinformatics Institute Variant Effect Predictor (VEP) tool for biological interpretation and the National Center for Biotechnology Information ClinVar tool for clinical interpretation.
  
  
  RESULTS
  An open-source desktop program was created to annotate incidental findings and present the results with a user-friendly interface. Further, a meaningful index (WHATIF Index) was devised for each gene to facilitate ranking of the relative importance of the variants and estimate the potential workload associated with further evaluation of the variants. Our WHATIF application is available at: http://tinyurl.com/WHATIF-SOFTWARE CONCLUSIONS: The WHATIF application offers a user-friendly interface and allows users to investigate the extracted variant information efficiently and intuitively while always accessing the up to date information on variants via application programming interfaces (API) connections. WHATIF׳s highly flexible design and straightforward implementation aids users in customizing the source code to meet their own special needs.
authors.affiliation: Biomedical Informatics Research Center, Marshfield Clinic Research Foundation, Marshfield, WI 54449, USA. Electronic address: ye.zhan@mcrf.mfldclin.edu.
authors.forename: Zhan
authors.initials: Z
authors.lastname: Ye
authors.affiliation: Biomedical Informatics Research Center, Marshfield Clinic Research Foundation, Marshfield, WI 54449, USA.
authors.forename: Christopher
authors.initials: C
authors.lastname: Kadolph
authors.affiliation: Biomedical Informatics Research Center, Marshfield Clinic Research Foundation, Marshfield, WI 54449, USA.
authors.forename: Robert
authors.initials: R
authors.lastname: Strenn
authors.affiliation: Biomedical Informatics Research Center, Marshfield Clinic Research Foundation, Marshfield, WI 54449, USA.
authors.forename: Daniel
authors.initials: D
authors.lastname: Wall
authors.affiliation: Department of Medical Genetics Services, Marshfield Clinic Research Foundation, Marshfield, WI 54449, USA.
authors.forename: Elizabeth
authors.initials: E
authors.lastname: McPherson
authors.affiliation: Biomedical Informatics Research Center, Marshfield Clinic Research Foundation, Marshfield, WI 54449, USA.
authors.forename: Simon
authors.initials: S
authors.lastname: Lin
mesh_terms: D000818:Animals; D014644:Genetic Variation; D059014:High-Throughput Nucleotide Sequencing; D006801:Humans; D017422:Sequence Analysis, DNA / Q000379:methods*; D014584:User-Computer Interface
keywords: Genomics; Internet; Sequencing; Software