Velo-Suarez, L. | bioRxiv Science

bioRxiv2022

Can imputation in a European country be improved by local reference panels? The example of France

France has a population with extensive internal fine-structure; and while public imputation reference panels contain an abundance of European genomes, there include few French genomes. Intuitively, using a study specific panel (SSP) for France would therefore likely be beneficial. To investigate, we imputed 550 French individuals using either the University of Michigan imputation server with the Haplotype Reference Consortium panel, or in-house using an SSP of 850 whole-genome sequenced French individuals. With approximate geo-localization of both our target and SSP individuals we are able to pinpoint different scenarios where SSP-based imputation would be preferred over server-based imputation or vice-versa. We could also show to a high degree of resolution how the proximity of the reference panel to a target individual determined the accuracy of both haplotype phasing and genotype imputation. Previous comparisons of different strategies have shown the benefits of combining public reference panels with SSPs. Getting the best out of both resources simultaneously is unfortunately impractical. We put forward a pragmatic solution where server-based and SSP-based imputation outcomes can be combined based on comparing posterior genotype probabilities. Such an approach can give a level of imputation accuracy markedly in excess of what could be achieved with either strategy alone.

genetics↗

bioRxiv2020

Evaluation of saliva as a source of accurate whole-genome and microbiome sequencing data

This study sets out to establish the suitability of saliva-based whole-genome sequencing (WGS) through a comparison against blood-based WGS. To fully appraise the observed differences, we developed a novel technique of pseudo-replicates. We also investigated the potential of characterising individual salivary microbiomes from non-human DNA fragments found in saliva. We observed the majority of discordant genotype calls between blood and saliva calls fell into known regions of the human genome that are typically sequenced with low confidence; and could be identified by quality control measures. Pseudo-replication demonstrated that the levels of discordance between blood- and saliva-derived WGS data were entirely similar to what one would expect between technical replicates if an individuals blood or saliva had been sequenced twice. Finally, we successfully sequenced salivary microbiomes in parallel to human genomes as demonstrated by a comparison against the Human Microbiome Project. Author SummaryDNA is usually collected from blood for the analysis of human genomes. In France, a new and very large genetic dataset will be created where selected participants will be sent saliva-collection kits in the post as this data collection method presents numerous logistical benefits. It has been previously shown that good quality genetic data can be created from saliva, though existing studies have often not considered the latest technologies or have only analysed a very small number of individuals. In this study, we have analysed genetic data derived from saliva for 39 individuals to give a firm conclusion that the proposed genome sequencing approach of the new French dataset will be capable of provided high quality data by making a comparison to pre-existing genetic data derived from blood for these 39 individuals. In order to do so, we developed a novel method (presented here) to establish the similarity between two sets of genetic data for the same individual that are generated from separate DNA samples. Finally, we have also demonstrated an added bonus of colleting saliva samples: that it is possible to gather both human genetic data and potentially interesting salivary microbiome data at the same time by separating and analysing in parallel human and non-human DNA fragments.

genetics↗