Christopher A. Walsh

Perinatal Elimination of Genetically Aberrant Neurons from Human Cerebral Cortex

The paper investigates somatic copy number variants (CNVs) in human neurons across development, finding that perinatal elimination of neurons with aberrant genomes reduces CNV prevalence and targets dosage-sensitive genes.

Systematic evaluation of incomplete penetrance in 4,325 rare disease families reveals divergent transcriptional networks in CHD8 pathology

The paper evaluates incomplete penetrance in 4,325 rare disease families, finding 1.6% of diagnosed cases involve inherited variants from unaffected parents and showing divergent transcriptional effects in CHD8-related cases.

Pervasive Somatic Mutations in NF1 Drive Cell Type and Spatially Specific Clonal Selection in Neurofibromatosis

The paper identifies pervasive somatic NF1 mutations in oligodendrocyte precursors in NF-1 patients, showing clonal selection and spatial bias, and links CDKN2A loss to tumor progression.

Somatic mutations and single-nucleus transcriptomics reveal uniquely human properties of neuronal aging

The paper compares somatic mutation rates and transcriptomic changes in neurons across six mammalian species, finding higher mutation accumulation and distinct age-related dysregulation in human neurons.

Pannexin-1 regulates cellular identity and excitability in the developing cortex

This study identifies de novo PANX1 mutations in individuals with PMG and microcephaly, showing they disrupt glycosylation, increase ATP release, and alter cortical development through ion conductance and cell fate regulation.

Recurrent patterns of TOP1-mediated neuronal genomic damage shared by major neurodegenerative disorders

The paper identifies a shared TOP1-mediated mutagenic mechanism in ALS, FTD, and AD through single-cell genomic analysis and experimental validation.

Somatic mutation in human cerebellum illustrates neuron type-specific patterns of age-related mutation

The paper analyzes somatic mutations in cerebellar granule neurons and finds distinct mutation patterns compared to other neuronal types, suggesting links to cancer origins and neurodegeneration.

Reconstructing multi-scale tissue spatial architecture from single-cell RNA-seq with REMAP

REMAP reconstructs spatial tissue architecture from scRNA-seq using deep learning and ST references, revealing microenvironmental features and cancer subtypes.

Activating Ras-MAPK pathway variants drive hippocampal clonal competition in human epilepsy

This study identifies somatic Ras-MAPK pathway variants in hippocampal tissue from patients with drug-resistant epilepsy, showing their association with clonal competition and worse surgical outcomes.

Biophysical basis for brain folding and misfolding patterns in ferrets and humans

The paper uses physical gel models and simulations to study brain folding in ferrets and links findings to human cortical malformations caused by genetic defects.

Benchmarking of duplex sequencing approaches to reveal somatic mutation landscapes

This study benchmarks six duplex sequencing technologies to evaluate their performance in detecting somatic mutations across different genomic contexts and tissue types.

A comprehensive view of somatic mosaicism by single-cell DNA analysis

The paper uses single-cell DNA sequencing to analyze somatic mosaicism in postmortem lung and colon tissues, revealing mutation heterogeneity, chromosomal abnormalities, and cellular ancestry.

Diverse somatic genomic alterations in single neurons in chronic traumatic encephalopathy

The paper identifies somatic genomic alterations in neurons from CTE patients, finding patterns similar to Alzheimer's disease and suggesting mechanisms beyond repetitive head impacts.

Unveiling causal regulatory mechanisms through cell-state parallax

The paper introduces GrID-Net, a graph neural network that detects causal locus-gene associations using cell-state parallax, uncovering noncoding mechanisms affecting 132 genes in schizophrenia.

Cell-type-informed genotyping of mosaic focal epilepsies reveals cell-autonomous and non-cell-autonomous disease-associated transcriptional programs

This study uses snRNA-seq and a new method called GO-TEN to analyze mosaic genetic variants in focal cortical dysplasia, revealing cell-autonomous and non-cell-autonomous transcriptional changes associated with epilepsy.

High-resolution detection of copy number alterations in single cells with HiScanner

HiScanner detects high-resolution copy number alterations in single cells, outperforming existing methods and revealing distinct CNA patterns in neurons and oligodendrocytes.

Cell-type-specific patterns and consequences of somatic mutation in development and aging brain

The paper introduces Duplex-Multiome, a method to identify cell-type-specific somatic mutations in brain tissue, revealing age-related mutation patterns and developmental lineage relationships.

Clonal Hematopoiesis Mutations Increase Risk of Alzheimer's Disease with APOE ϵ3/ϵ3 Genotype

This study finds that Alzheimer's disease patients have more clonal hematopoiesis mutations than controls, especially those with APOE ε3/ε3 genotype, suggesting a risk factor independent of APOE ε4.

FOS binding sites are a hub for the evolution of activity-dependent gene regulatory programs in human neurons

The paper identifies human-specific activity-dependent genes regulated by FOS-bound enhancers, showing their role in human brain development evolution.

Human-chimpanzee tetraploid system defines mechanisms of species-specific neural gene regulation

The paper uses human-chimpanzee tetraploid cells to identify cis-acting gene regulatory changes contributing to human neural specializations.

Transcriptomic Convergence and the Female Protective Effect in Autism

This study shows that perturbations of ASD genes in human neural progenitor cells converge on shared transcriptomic effects, with ZFX potentially mediating the female protective effect.

Neuropathologically-directed profiling of PRNP somatic and germline variants in sporadic human prion disease

This study investigates whether somatic mutations in PRNP contribute to sporadic Creutzfeldt-Jakob Disease (sCJD) by sequencing PRNP in 205 sCJD cases and 170 controls, finding no evidence of pathogenic somatic variants.

Rare germline disorders implicate long non-coding RNAs disrupted by chromosomal structural rearrangements

The paper identifies chromosomal structural rearrangements disrupting long non-coding RNAs (lncRNAs) in individuals with rare germline disorders, highlighting potential pathogenic roles of lncRNA disruptions.

Spatial Single-cell Analysis Decodes Cortical Layer and Area Specification

The paper uses spatial single-cell analysis to uncover molecular and structural development of human fetal cortex, revealing early layer and area specification.

Cell-type-specific effects of autism-associated chromosome 15q11.2-13.1 duplications in human brain

This study examines how dup15q affects gene expression and chromatin accessibility in specific brain cell types, finding cell-type-specific effects and distinct regulatory mechanisms in ASD and dup15q.

Exome copy number variant detection, analysis and classification in a large cohort of families with undiagnosed rare genetic disease

The paper detects and classifies copy number variants in exome data from 6,633 families, identifying causal CNVs in 173 families and improving classification standards.

ARX regulates cortical interneuron differentiation and migration

This study investigates ARX's role in cortical interneuron development and migration, identifying its regulatory impact on proliferation, fate specification, and cell-cell communication.

Somatic cancer driver mutations are enriched and associated with inflammatory states in Alzheimer's disease microglia

The paper identifies somatic driver mutations in microglia of Alzheimer's disease brains, showing increased clonal expansion and inflammatory signatures.

Somatic mosaicism in amyotrophic lateral sclerosis and frontotemporal dementia identifies focal mutations associated with widespread degeneration

The paper identifies rare somatic mutations in sporadic ALS and FTD cases, suggesting they contribute to disease and widespread neurodegeneration.

Cell lineage analysis with somatic mutations reveals late divergence of neuronal cell types and cortical areas in human cerebral cortex

The paper uses somatic mutations to analyze lineage divergence in human cortical regions, finding late divergence of neuronal cell types and regional inhomogeneities in progenitor proliferation.