Nicola Whiffin

The paper evaluates precomputed SpliceAI scores for splice-altering variant prioritization in NDD cohorts, finding inaccuracies and providing a tool to improve variant triage.

The paper identifies a cross-tissue splicing signature as a biomarker for ReNU syndrome, distinguishing affected individuals from controls with high specificity.

The paper provides guidance for classifying variants in snRNA genes and introduces RNUdb, a tool to support variant annotation and classification.

The paper develops ASO Atlas, a database of RNase H-mediated ASO sequences and their efficacy, and trains OligoAI, a deep learning model to predict ASO efficacy based on sequence and chemical features, reducing screening effort by 5.72-fold.

The paper creates a genome-wide map of homozygous deletions in 125,730 individuals, identifying novel rare disease genes and variants.

The paper identifies biallelic variants in RNU2-2 as a frequent cause of a severe developmental epileptic encephalopathy, distinct from a dominant disorder, and links them to reduced U2-2 abundance.

This study identifies 5'UTR exons containing uORFs as targets for splice-switching to increase protein translation in haploinsufficient disease genes.

The paper identifies biallelic variants in RNU4-2 causing a recessive neurodevelopmental syndrome with distinct white matter changes, expanding the known genotypic and phenotypic spectrum of RNU4-2-related disorders.

The paper improves aberrant splicing variant prediction across developmental stages and identifies developmentally restricted variants linked to neurodevelopmental disorders.

This study uses saturation genome editing to analyze RNU4-2 variants, identifying functional impacts and redefining the ReNU syndrome critical region.

This study uses whole genome sequencing to identify causative variants in mutation-negative Cornelia de Lange Syndrome patients, finding novel genes and regulatory regions involved.

The paper identifies regional nonsense constraint in the human genome using sequencing data, showing enriched de novo variants in constrained regions linked to rare diseases.

The paper introduces PS4-LRCalc, a tool that quantitatively assigns evidence for variant classification using case-control data, enabling continuous scoring instead of dichotomous PS4 scoring.

This study identifies a cryptic exon in the human PRNP gene that can reduce prion protein expression when included in mRNA, offering a new therapeutic target for prion disease.

The paper identifies compound heterozygous variants in UK Biobank data and shows their phenotypic impact on common diseases using statistical phasing and mixed models.

This paper introduces Ribosome Decision Graphs (RDGs) to represent eukaryotic RNA translation complexity, enabling analysis of translation patterns and genetic variation effects.

The paper examines 5' untranslated regions (UTRs) to show their role in translational regulation of dosage-sensitive genes and introduces a web tool for analyzing 5UTR composition.

This paper standardizes terminology for describing disease-gene relationships to improve variant classification and genetic test interpretation.

This study identifies disease-causing promoter and untranslated region variants in 8,040 undiagnosed rare disease patients using a new framework and finds 12 variants with potential pathogenicity.

This paper introduces Paralogue Annotation, a method using homologous protein variants to predict disease-causing missense variants with high precision.

The paper identifies non-coding variants in trans with coding variants in patients with developmental disorders, finding them to be a rare cause of recessive disorders.

This study analyzes splicing variants in whole-genome sequencing data to identify new diagnoses in rare diseases.

This paper provides recommendations for interpreting non-coding variants in clinical settings, adapting existing guidelines to account for their role in disease.

This paper introduces HMC, a high-resolution genetic constraint score for missense variants, improving variant prioritization and gene discovery for developmental disorders.

The paper introduces MRSD, a metric to determine optimal RNA-seq depth and tissue for assessing splicing variants in Mendelian diseases, showing LCLs are best for most gene panels.

This study examines the clinical impact of rare variants in HCM-associated genes in the UK Biobank, finding that pathogenic variants are linked to increased cardiovascular risk and subclinical phenotypes, while non-pathogenic variants show minimal effect.

The paper identifies a frameshift variant in MYH7 associated with HCM in an Egyptian cohort, revealing a new pathogenic mechanism involving distal PTC escape from NMD.

The paper identifies non-coding variants upstream of MEF2C causing severe developmental disorder through three distinct loss-of-function mechanisms, showing their diagnostic importance in existing exome datasets.

The paper describes the EHVol study, a genomic database of 391 Egyptian healthy volunteers to improve representation in global genomic databases and aid in variant interpretation for North African populations.

This paper introduces CardioBoost, a disease-specific variant classifier for inherited cardiac conditions, showing improved accuracy in predicting pathogenicity compared to genome-wide tools.