Deep whole-genome sequencing of 100 southeast Asian Malays.

Whole-genome sequencing across multiple samples in a population provides an unprecedented opportunity for comprehensively characterizing the polymorphic variants in the population. Although the 1000 Genomes Project (1KGP) has offered brief insights into the value of population-level sequencing, the low coverage has compromised the ability to confidently detect rare and low-frequency variants. In addition, the composition of populations in the 1KGP is not complete, despite the fact that the study design has been extended to more than 2,500 samples from more than 20 population groups. The Malays are one of the Austronesian groups predominantly present in Southeast Asia and Oceania, and the Singapore Sequencing Malay Project (SSMP) aims to perform deep whole-genome sequencing of 100 healthy Malays. By sequencing at a minimum of 30× coverage, we have illustrated the higher sensitivity at detecting low-frequency and rare variants and the ability to investigate the presence of hotspots of functional mutations. Compared to the low-pass sequencing in the 1KGP, the deeper coverage allows more functional variants to be identified for each person. A comparison of the fidelity of genotype imputation of Malays indicated that a population-specific reference panel, such as the SSMP, outperforms a cosmopolitan panel with larger number of individuals for common SNPs. For lower-frequency (<5%) markers, a larger number of individuals might have to be whole-genome sequenced so that the accuracy currently afforded by the 1KGP can be achieved. The SSMP data are expected to be the benchmark for evaluating the value of deep population-level sequencing versus low-pass sequencing, especially in populations that are poorly represented in population-genetics studies.

Assessment of Web-Based Consumer Reviews as a Resource for Drug Performance.

BACKGROUND: Some health websites provide a public forum for consumers to post ratings and reviews on drugs. Drug reviews are easily accessible and comprehensible, unlike clinical trials and published literature. Because the public increasingly uses the Internet as a source of medical information, it is important to know whether such information is reliable. OBJECTIVE: We aim to examine whether Web-based consumer drug ratings and reviews can be used as a resource to compare drug performance. METHODS: We analyzed 103,411 consumer-generated reviews on 615 drugs used to treat 249 disease conditions from the health website WebMD. Statistical analysis identified 427 drug pairs from 24 conditions for which two drugs treating the same condition had significantly and substantially different satisfaction ratings (with at least a half-point difference between Web-based ratings and P<.01). PubMed and Google Scholar were searched for publications that were assessed for concordance with findings online. RESULTS: Scientific literature was found for 77 out of the 427 drug pairs and compared to findings online. Nearly two-thirds (48/77, 62%) of the online drug trends with at least a half-point difference in online ratings were supported by published literature (P=.02). For a 1-point online rating difference, the concordance rate increased to 68% (15/22) (P=.07). The discrepancies between scientific literature and findings online were further examined to obtain more insights into the usability of Web-based consumer-generated reviews. We discovered that (1) drugs with FDA black box warnings or used off-label were rated poorly in Web-based reviews, (2) drugs with addictive properties were rated higher than their counterparts in Web-based reviews, and (3) second-line or alternative drugs were rated higher. In addition, Web-based ratings indicated drug delivery problems. If FDA black box warning labels are used to resolve disagreements between publications and online trends, the concordance rate increases to 71% (55/77) (P<.001) for a half-point rating difference and 82% (18/22) for a 1-point rating difference (P=.002). Our results suggest that Web-based reviews can be used to inform patients' drug choices, with certain caveats. CONCLUSIONS: Web-based reviews can be viewed as an orthogonal source of information for consumers, physicians, and drug manufacturers to assess the performance of a drug. However, one should be cautious to rely solely on consumer reviews as ratings can be strongly influenced by the consumer experience.