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Standardized interfaces for efficiently accessing high-throughput sequencing data are a fundamental requirement for large-scale genomic data sharing. We have developed htsget, a protocol for secure, efficient and reliable access to sequencing read and variation data. We demonstrate four independent client and server implementations, and the results of a comprehensive interoperability demonstration.doi:10.1093/bioinformatics/bty492 pmid:29931085 pmcid:PMC6298043 fatcat:slz7ksxtjffl5e7bnbfcj5t24m