Qianyao Zhang, Runtong Zhang, Xinyi Lu, Xijing Zhang
What drives the adoption of online health communities? An empirical study from patient-centric perspective
BMC health services research
major obstacle faced families rare diseases obtaining genetic diagnosis average diagnostic odyssey lasts five years causal variants identified 50 even capturing variants genomewide aid interpretation prioritization vast number variants detected computational methods proliferating knowing tools effective remains unclear evaluate performance computational methods encourage innovation method development designed critical assessment genome interpretation cagi community challenge place variant prioritization models headtohead reallife clinical diagnostic setting utilized genome sequencing gs data families sequenced rare genomes project rgp directtoparticipant research study utility gs rare disease diagnosis gene discovery challenge predictors provided dataset variant calls phenotype terms 175 rgp individuals 65 families including 35 solved training set families causal variants specified 30 unlabeled test set families 14 solved 16 unsolved tasked teams identify causal variants many families possible predictors submitted variant predictions estimated probability causal relationship epcr values model performance determined two metrics weighted score based rank position causal variants maximum fmeasure based precision recall causal variants across epcr values sixteen teams submitted predictions 52 models manual review incorporated top performers recalled causal variants 13 14 solved families within top 5 ranked variants newly discovered diagnostic variants returned two previously unsolved families following confirmatory rna sequencing two novel disease gene candidates entered matchmaker exchange one example rna sequencing demonstrated aberrant splicing due deep intronic indel asns identified trans frameshift variant unsolved proband phenotypes consistent asparagine synthetase deficiency model methodology performance highly variable models weighing call quality allele frequency predicted deleteriousness segregation phenotype effective identifying causal variants models open phenotype expansion noncoding variants able capture difficult diagnoses discover new diagnoses overall computational models significantly aid variant prioritization use diagnostics detailed review conservative assessment prioritized variants established criteria needed