Technical Reports

CT-SLEB, a powerful and scalable method, improves the performance of multiancestry polygenic prediction by generating polygenic risk scores based on GWAS summary statistics in diverse populations.

Simulations and applications to real data show that adjustment of genome-wide association analyses for polygenic scores increases the statistical power for discovery across all ancestries, suggesting an analytical strategy for future studies in underrepresented populations.

GATK-gCNV uses a probabilistic model and inference framework to discover rare copy number variants (CNVs) from sequencing read-depth information. This algorithm is used to generate a reference catalog of rare coding CNVs in exome sequencing data from UK Biobank.

PhenoScore is an open-source machine-learning tool that combines facial image recognition with Human Phenotype Ontology for genetic syndrome identification without genomic data, with applications to subgroup analysis and variants of unknown significance classification.

A new methodology to study participation genetics via analyzing shared and unshared genotypes is applied to the UK Biobank, suggesting that participating in genetic studies is a complex trait with a meaningful genetic component.

SHAPEIT5, a phasing method that accurately processes large sequencing datasets, was applied on the UK Biobank whole-genome and whole-exome sequencing data to generate reference panels of haplotypes that boost imputation accuracy and enable the detection of compound heterozygous loss-of-function events for 549 genes.

GASPACHO is a statistical method that identifies nonlinear dynamic genetic effects using single-cell RNA-seq data. Analysis of an antiviral response in human fibroblasts identifies 1,275 expression QTLs, many of which colocalize with risk loci for autoimmune and infectious diseases.

Causal robust mapping method in meta-analysis (CARMA) studies incorporates flexible prior distributions, joint modeling of summary statistics and functional annotations and outlier detection for improved causal variant fine-mapping in genome-wide association meta-analyses.

Region Capture Micro-C (RCMC) combines MNase-based 3C with a tiling region-capture method. Profiling mouse embryonic stem cells with RCMC identifies nested microcompartments, which connect enhancers and promoters.

scEC&T-seq profiles extrachromosomal circular DNA and full-length mRNA from single human cancer cells, and may be used to interrogate heterogeneity in both cell lines and primary tumor samples.

AbSplice predicts aberrant splicing for 50 human tissues by integrating sequence-based deep learning models, DNA variation and RNA-seq obtained from accessible tissues.

Concatenating Original Duplex for Error Correction (CODEC) is a method that concatenates both strands of each DNA duplex to enable highly sensitive mutation detection in a range of analytes with fewer reads and lower error rates than current methods.

A single-cell massively parallel reporter assay is used to compare cis-regulatory sequence activities in cell line models and mouse retinal tissue ex vivo, identifying cell state- and cell-type-specific effects of sequence variation.

MetaSTAAR enables functionally informed rare variant association analysis in biobank-scale cohorts using an efficient, sparse matrix approach for summary statistic storage.

Sort-assisted single-cell chromatin immunocleavage (sortChIC) combines single-cell histone modification profiling with fluorescence-activated cell sorting (FACS), enabling the study of rare cell populations. H3K4me1/H3K4me3, H3K9me3 and H3K27me3 profiling of blood suggest a model of lineage-shared repressive and cell type-specific active chromatin.

CRISPR-Select is a quantitative assay for the functional impact of genetic variants, including pathogenicity, drug response, oncogenicity, cell motility and other cell states.

CRISPR-CATCH is used to isolate extrachromosomal DNA (ecDNA) molecules containing oncogenes from human cancer cells. CRISPR-CATCH followed by nanopore sequencing allows for methylation profiling, highlighting differences from the native chromosomal loci.

Single-cell DNA sequencing data are generated from human neurons using primary template-directed amplification and analyzed using SCAN2, an improved genotyping tool. Indels are enriched in neuronal regulatory elements and may be deleterious.

scDRS associates individual cells in scRNA-seq with disease by scoring single-cell transcriptomes using GWAS gene signatures. Applied to 74 GWAS and 1.3 million single-cell profiles, scDRS identifies specific cellular subpopulations associated with these diseases.

snipar is a software package for imputing missing parental genotypes and estimating direct genetic effects. Application to UK Biobank data shows that effects estimated by standard genome-wide association study designs have confounding bias for some phenotypes.