Devon E. Bonner

Integrating sequence-to-omics predictions and personal multi-omics for rare variant prioritization

The paper introduces Watershed-DL, a framework integrating sequence-to-omics predictions and multi-omics data to prioritize rare variants, finding it increases prioritized variants by 61.4% and identifies candidate disease alleles.

MetaDome 2027: a comprehensively updated resource for aggregating missense variant evidence across homologous human protein domains

MetaDome now supports GRCh38 alongside GRCh37, adds coordinate lookup, and identifies 52,463 GRCh38 ClinVar missense variants of uncertain significance with uncontradicted pathogenic evidence at homologous Pfam-domain positions.

Domain specific phenotypic expansion associated with variants in MACF1

The paper identifies domain-specific phenotypic effects of MACF1 variants outside the GAR domain, revealing broader neurodevelopmental and craniofacial anomalies.

Uncovering Phenotypic Expansion in AXIN2-Related Disorders Using Precision Animal Modeling

The paper identifies novel AXIN2 variants causing expanded phenotypes in humans and validates their pathogenicity using human, mouse, and fly models.

Population-scale detection of methylation outliers from long-read genome sequencing

METAFORA calls depth-aware, covariate-adjusted methylation outlier regions from PacBio and Nanopore long reads; in 551 rare-disease genomes, outliers tracked structural variants, repeat expansions, and imprinting defects.

Biallelic variants in RNU2-2 cause the most prevalent known recessive neurodevelopmental disorder

The paper identifies biallelic variants in RNU2-2 as a common cause of recessive neurodevelopmental disorders, showing higher prevalence than the dominant form in England.

An optimized variant prioritization process for rare disease diagnostics: recommendations for Exomiser and Genomiser

This paper optimizes variant prioritization parameters for Exomiser and Genomiser to improve diagnostic yield in rare disease cases using WES and WGS data.

Transcriptome-wide outlier approach identifies individuals with minor spliceopathies

The paper identifies individuals with minor spliceopathies by analyzing transcriptome-wide splicing outliers in RNA-seq data from rare disease cohorts.

Joint, multifaceted genomic analysis enables diagnosis of diverse, ultra-rare monogenic presentations

The paper presents a joint genomic analysis of UDN patients using whole genome sequencing and new statistical methods to prioritize disease genes, revealing new disease associations and releasing a software tool for cohort analysis.

Integration of transcriptomics and long-read genomics prioritizes structural variants in rare disease

The paper integrates long-read sequencing and gene expression to prioritize functional structural variants and tandem repeats in rare disease patients, identifying potential causal variants in a neurodevelopmental disorder.

De novo variants in KDM2A cause a syndromic neurodevelopmental disorder

This study identifies de novo KDM2A variants as a cause of a syndromic neurodevelopmental disorder with specific clinical features and functional consequences.

Considerations for reporting variants in novel candidate genes identified during clinical genomic testing

The paper develops criteria for identifying, sharing, and reporting novel candidate genes in clinical genomic testing to improve diagnostic yield for Mendelian conditions.

Impact of genome build on RNA-seq interpretation and diagnostics

This study examines how different genome builds affect RNA-seq results in rare disease samples and recommends cross-referencing with a database of build-dependent genes for more accurate transcriptomics analysis.

Clinical application of Complete Long Read genome sequencing identifies a 16kb intragenic duplication in EHMT1 in a patient with suspected Kleefstra syndrome

The paper applies complete long read sequencing to undiagnosed patients, identifying a 16kb intragenic duplication in EHMT1 causing Kleefstra syndrome.

DPP9 deficiency: an inflammasomopathy which can be rescued by lowering NLRP1/IL-1 signaling

This study identifies DPP9 deficiency as a Mendelian disorder causing inflammasome hyperactivity, which can be rescued by reducing NLRP1/IL-1 signaling in mice.

DEFINING THE DIVERSITY OF HNRNPA1 MUTATIONS IN CLINICAL PHENOTYPE AND PATHOMECHANISM

The paper characterizes HNRNPA1 mutations in patients with neurodegenerative diseases, showing varied effects on fibrillization, phase separation, and stress granule dynamics.

Variants in PRKAR1B cause a neurodevelopmental disorder with autism spectrum disorder, apraxia, and insensitivity to pain

The paper identifies de novo PRKAR1B variants in six individuals with neurodevelopmental disorder, autism, apraxia, and reduced pain sensitivity.

Systematic assessment of regulatory effects of human disease variants in pluripotent cells

The paper maps regulatory effects of human disease variants in pluripotent cells, identifying cis- and trans-QTL across 18,556 genes and linking them to GWAS traits.

AMELIE 3: Fully Automated Mendelian Patient Reanalysis at Under 1 Alert per Patient per Year

AMELIE 3 automatically reanalyzes undiagnosed Mendelian disease patients using new literature, achieving 80% diagnostic yield with 0.5-1 alerts per patient per year.

De novo EIF2AK1 and EIF2AK2 variants are associated with developmental delay, leukoencephalopathy, and neurologic decompensation

The paper identifies de novo variants in EIF2AK1 and EIF2AK2 associated with neurodevelopmental disorders and leukoencephalopathy, showing similar pathogenic mechanisms to CACH/VWM.

Machine learning-based detection of insertions and deletions in the human genome

This paper introduces machine learning tools for improved indel detection in the human genome, achieving high precision and recall in clinical applications.

Identification of Pathogenic Structural Variants in Rare Disease Patients through Genome Sequencing

This paper identifies pathogenic structural variants in rare disease patients using whole genome sequencing and reports their clinical relevance.

Identification of rare-disease genes in diverse undiagnosed cases using whole blood transcriptome sequencing and large control cohorts

This study evaluates the use of whole blood transcriptome sequencing for diagnosing rare diseases, finding an 8.5% diagnostic rate across 56 undiagnosed cases.

Loss-of-function in IRF2BPL is associated with neurological phenotypes

This study identifies damaging variants in IRF2BPL associated with neurological phenotypes in humans and shows functional conservation in fruit flies.