Chris Wallace
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View article: Semi-supervised Bayesian integration of multiple spatial proteomics datasets
Semi-supervised Bayesian integration of multiple spatial proteomics datasets Open
The subcellular localisation of proteins is a key determinant of their function. High-throughput analyses of these localisations can be performed using mass spectrometry-based spatial proteomics, which enables us to examine the localisatio…
View article: Variable information across SNPs in GWAS data can cause false rejections of colocalisation which can be resolved by proportional colocalisation tests
Variable information across SNPs in GWAS data can cause false rejections of colocalisation which can be resolved by proportional colocalisation tests Open
Fine-mapping is now a standard post-GWAS analysis, but it has been shown to be potentially inaccurate for large meta-analysis GWAS. We show how this can be caused by variable amounts of statistical information between variants, e.g. due to…
Cell-type-resolved genetic regulatory variation shapes inflammatory bowel disease risk Open
Most genetic variants associated with complex diseases lie in non-coding regions, complicating efforts to identify effector genes and relevant cell types. Here, we map cis-eQTLs across 2.2 million single cells from blood and intestinal bio…
Variant-specific priors clarify colocalisation analysis Open
Linking GWAS variants to their causal gene and context remains an ongoing challenge. A widely used method for performing this analysis is the coloc package for statistical colocalisation analysis, which can be used to link GWAS and eQTL as…
Identification and validation of interferon-driven gene signature as a predictor of response to methotrexate in juvenile idiopathic arthritis Open
In children with JIA, a high IFN-driven gene signature is associated with a better response to MTX than those with a low IFN-driven gene signature. These data could pave the way to clinically validated tools to identify those most likely t…
Penalised regression improves imputation of cell-type specific expression using RNA-seq data from mixed cell populations compared to domain-specific methods Open
Gene expression studies often use bulk RNA sequencing of mixed cell populations because single cell or sorted cell sequencing may be prohibitively expensive. However, mixed cell studies may miss expression patterns that are restricted to s…
Outcome-guided spike-and-slab Lasso Biclustering: A Novel Approach for Enhancing Biclustering Techniques for Gene Expression Analysis Open
Biclustering has gained interest in gene expression data analysis due to its ability to identify groups of samples that exhibit similar behaviour in specific subsets of genes (or vice versa), in contrast to traditional clustering methods t…
View article: Tandem repeat variation shapes immune cell type-specific gene expression
Tandem repeat variation shapes immune cell type-specific gene expression Open
Tandem repeats (TRs) - highly polymorphic, repetitive sequences across the human genome - are important regulators of gene expression but remain underexplored due to challenges in accurate genotyping and analysis. Here, we generate new who…
View article: Performance of deep-learning based approaches to improve polygenic scores
Performance of deep-learning based approaches to improve polygenic scores Open
Background/Objectives Polygenic scores (PGS), which estimate an individual’s genetic propensity for a disease or trait, have the potential to become part of genomic healthcare. In maximising the predictive performance of PGS, neural-networ…
MDA5 variants trade antiviral activity for protection from autoimmune disease Open
Loss-of-function variants in MDA5, a key sensor of double-stranded RNA from viruses and retroelements, have been associated with protection from type 1 diabetes (T1D) in genome-wide association studies (GWAS). MDA5 loss-of-function variant…
Exploiting pleiotropy to enhance variant discovery with functional false discovery rates Open
The cost of acquiring participants for genome-wide association studies (GWAS) can limit sample sizes and inhibit discovery of genetic variants. We introduce the surrogate functional false discovery rate (sfFDR) framework which integrates s…
Bayesian clustering with uncertain data Open
Clustering is widely used in bioinformatics and many other fields, with applications from exploratory analysis to prediction. Many types of data have associated uncertainty or measurement error, but this is rarely used to inform the cluste…
Variant-specific priors in colocalisation analysis Open
Linking GWAS variants to their causal gene remains an ongoing challenge. A widely used method for performing this analysis is the coloc package for statistical colocalisation analysis, which can be used to link GWAS and eQTL associations. …
View article: Discovery of new myositis genetic associations through leveraging other immune-mediated diseases
Discovery of new myositis genetic associations through leveraging other immune-mediated diseases Open
Genome-wide association studies (GWASs) have been successful at finding associations between genetic variants and human traits, including the immune-mediated diseases (IMDs). However, the requirement of large sample sizes for discovery pos…
View article: A Genome‐Wide Association Study Suggests New Susceptibility Loci for Primary Antiphospholipid Syndrome
A Genome‐Wide Association Study Suggests New Susceptibility Loci for Primary Antiphospholipid Syndrome Open
Objective Primary antiphospholipid syndrome (PAPS) is a rare autoimmune disease characterized by the presence of antiphospholipid antibodies and the occurrence of thrombotic events and pregnancy complications. Our study aimed to identify n…
Leveraging pleiotropy identifies common-variant associations with selective IgA deficiency Open
Selective IgA deficiency (SIgAD) is the most common inborn error of immunity (IEI). Unlike many IEIs, evidence of a role for highly penetrant rare variants in SIgAD is lacking. Known SIgAD-associated variants are common in the general popu…
colocPropTest: Proportional Testing for Colocalisation Analysis Open
Colocalisation analysis tests whether two traits share a causal genetic variant in a specified genomic region. Proportional testing for colocalisation has been previously proposed [Wallace (2013) ], but is reimplemented here to overcome ba…
View article: A disease-associated gene desert directs macrophage inflammation through ETS2
A disease-associated gene desert directs macrophage inflammation through ETS2 Open
Increasing rates of autoimmune and inflammatory disease present a burgeoning threat to human health 1 . This is compounded by the limited efficacy of available treatments 1 and high failure rates during drug development 2 , highlighting an…
P096 Pathway directionality across different immune cell lineages contributes to methotrexate response in juvenile idiopathic arthritis Open
Background/Aims Juvenile idiopathic arthritis (JIA) is the most common autoimmune rheumatic disease in children with methotrexate (MTX) as the first line treatment. However, about 50% of JIA patients will not respond well to MTX yet still …