Identifying genomic variants is a fundamental first step toward the 
understanding of the role of inherited and acquired variation in disease. The 
accelerating growth in the corpus of sequencing data that underpins such 
analysis is making the data-download bottleneck more evident, placing 
substantial burdens on the research community to keep pace. As a result, the 
search for alternative approaches to the traditional "download and analyze" 
paradigm on local computing resources has led to a rapidly growing demand for 
cloud-computing solutions for genomics analysis. Here, we introduce the Genome 
Variant Investigation Platform (GenomeVIP), an open-source framework for 
performing genomics variant discovery and annotation using cloud- or local 
high-performance computing infrastructure. GenomeVIP orchestrates the analysis 
of whole-genome and exome sequence data using a set of robust and popular 
task-specific tools, including VarScan, GATK, Pindel, BreakDancer, Strelka, and 
Genome STRiP, through a web interface. GenomeVIP has been used for genomic 
analysis in large-data projects such as the TCGA PanCanAtlas and in other 
projects, such as the ICGC Pilots, CPTAC, ICGC-TCGA DREAM Challenges, and the 
1000 Genomes SV Project. Here, we demonstrate GenomeVIP's ability to provide 
high-confidence annotated somatic, germline, and de novo variants of potential 
biological significance using publicly available data sets.