Efficient phasing and imputation of low-coverage sequencing data using large reference panels

In this work, we address the challenge of genotype imputation and haplotype phasing of low-coverage sequencing datasets using a reference panel of haplotypes. To this aim, we propose a novel method, GLIMPSE (Genotype Likelihoods Imputation and PhaSing mEthod), that is designed for large-scale studies and reference panels, typically comprising thousands of genomes. We show the remarkable performance of GLIMPSE using low-coverage whole genome sequencing data for both European and African American populations, and we demonstrate that low-coverage sequencing can be confidently used in downstream analyses. We provide GLIMPSE as a part of an open source software suite that makes imputation for low-coverage sequencing data as convenient as for traditional SNP array platforms.

Press covering the GLIMPSE paper

Following the pubblication on Nature Genetics, the Swiss Institute of Bioinformatics (SIB) released an article about GLIMPSE and its applications. Other media, RTS radio and covered the news.

The molecular basis, genetic control and pleiotropic effects of local gene co-expression

In this work, we investigate how local gene co-expression leads to pleiotropy and comorbidity and provide functional interpretation of QTL and GWAS findings.

Genotype imputation using the Positional Burrows Wheeler Transform

Genome-wide association studies (GWAS) typically use microarray technology to measure genotypes at several hundred thousand positions in the genome. However reference panels of genetic variation consist of haplotype data at 100 fold more positions in the genome. Genotype imputation makes genotype predictions at all the reference panel sites using the GWAS data. Reference panels are continuing to grow in size and this improves accuracy of the predictions, however methods need to be able to scale this increased size. We have developed a new version of the popular IMPUTE software than can handle reference panels with millions of haplotypes, and has better performance than other published approaches. A notable property of the new method is that it scales sub-linearly with reference panel size. Keeping the number of imputed markers constant, a 100 fold increase in reference panel size requires less than twice the computation time.

High-throughput SARS-CoV-2 and host genome sequencing from single nasopharyngeal swabs

We developed a scalable, high throughput approach to generate high fidelity low pass whole genome and HLA sequencing, viral genomes, and representation of human transcriptome from single nasopharyngeal swabs of COVID19 patients.