Johnathan Cooper‐Knock

Pathology-defined cell states reveal reproducible transcriptomic signatures across ALS cortical single-nucleus RNA-seq studies

The paper shows that using pathology-defined cell states improves reproducibility of transcriptomic signatures in ALS snRNA-seq studies compared to conventional case-control analyses.

Human Body Single-Cell Atlas of 3D Genome Organization and DNA Methylation

The paper maps 3D genome organization and DNA methylation across 86,689 single nuclei from 16 human tissues, revealing cell-type-specific variations and discrepancies between methylation and chromatin structure.

Astrocyte dysfunction distinguishes monozygotic twin C9orf72 expansion carriers discordant for amyotrophic lateral sclerosis.

This study identifies distinct astrocyte states in C9orf72 expansion carriers discordant for ALS, linking epigenetic changes, stress, and functional dysfunction to disease onset.

ProMeta: A meta-learning framework for robust disease diagnosis and prediction from plasma proteomics

ProMeta improves disease diagnosis and prediction from plasma proteomics using a meta-learning framework that overcomes data scarcity with biological priors and interpretable features.

STMN2 protein depletion via translation deficits and stress granules and its compensation in ALS

This study identifies TDP-43-independent mechanisms of STMN2 depletion in ALS, showing acute stress causes proteasomal degradation and translational repression, while chronic stress leads to reduced protein levels, with mRNA upregulation as a compensatory mechanism in some subtypes.

PRSNet-2: End-to-end genotype-to-phenotype prediction via hierarchical graph neural networks

PRSNet-2 predicts complex phenotypes from genotypic data using a hierarchical graph neural network, outperforming baselines and reducing overfitting.

Amyotrophic Lateral Sclerosis-associated 3' UTR enhancer embedded within CAV1 risk gene

The paper identifies an ALS-associated enhancer within the CAV1 3' UTR, showing how non-coding variants disrupt enhancer function at multiple regulatory levels.

TDP-43 toxic gain of function links ALS, FTD and Alzheimers Disease through splicing dysregulation

This study identifies TDP-43-driven splicing dysregulation as a common mechanism in ALS, FTD, and Alzheimer's disease, linking them through mis-spliced mRNAs like APP.

Dissecting the genetic complexity of myalgic encephalomyelitis/chronic fatigue syndrome via deep learning-powered genome analysis

This study uses a deep learning framework to analyze whole-genome data from ME/CFS patients, identifying risk genes and linking them to disease symptoms and other complex traits.

Towards a diagnostic test for sporadic ALS utilising deep learning and SNP microarrays

This paper develops a deep learning model using SNP microarray data to predict ALS risk with high accuracy across diverse populations and genotyping platforms.

A multistage, multitask transformer-based framework for multi-disease diagnosis and prediction using personal proteomes

Prophet is a transformer-based framework that improves disease diagnosis and prediction using proteomics data from the UK Biobank, achieving high accuracy and identifying new protein-disease associations.

The oligogenic structure of amyotrophic lateral sclerosis has genetic testing, counselling, and therapeutic implications

The paper investigates oligogenic risk in ALS using genome sequencing data, finding that multiple rare variants in known ALS genes increase disease risk but not clinical outcomes.

Sex-specific DNA methylation differences in Amyotrophic lateral sclerosis

The paper identifies sex-associated DNA methylation differences in ALS using a large-scale epigenome-wide association study and links them to survival outcomes.

predicTTE: An accessible and optimal tool for time-to-event prediction in neurological diseases

The paper introduces predicTTE, a tool for time-to-event prediction in neurological diseases, demonstrating its utility in genetic discovery and personalized medicine.

Computing Linkage Disequilibrium Aware Genome Embeddings using Autoencoders

The paper introduces a method to compress genetic data using autoencoders that leverage linkage disequilibrium structure, achieving high reconstruction accuracy while reducing data size.

Deconvolution of polygenic risk score in single cells unravels cellular and molecular heterogeneity of complex human diseases

This paper introduces scPRS, a deep learning model that deconvolves polygenic risk scores at the single-cell level to uncover cellular and molecular disease mechanisms in complex human diseases.

Antisense oligonucleotide depletion of CCDC146 is a broad-spectrum therapeutic strategy for ALS

The paper identifies CCDC146 as a modifier of ALS survival through primary cilia dysfunction and shows ASO targeting of CCDC146 rescues ALS phenotypes in human and mouse models.

GRASPS: a simple-to-operate translatome technology reveals omics-hidden disease-associated pathways in TDP-43-related amyotrophic lateral sclerosis

GRASPS identifies more differentially expressed transcripts with higher fold changes and significance in TDP-43 ALS models, revealing previously missed disease pathways.

hnRNPUL1 ensures efficient Integrator-mediated cleavage of snRNAs and is mutated in amyotrophic lateral sclerosis

This study identifies hnRNPUL1's role in Integrator-mediated snRNA cleavage and links its mutations to amyotrophic lateral sclerosis.

Functional clustering of splice-altering variants in whole genome sequencing data reveals hidden heritability in rare variant disorder

SpliPath identifies pathogenic splice-altering variants in ALS by integrating SpliceAI predictions with transcriptomics data, revealing hidden heritability in rare variant disorders.

Clinical testing panels for ALS: global distribution, consistency, and challenges

The paper evaluates the variability in ALS clinical genetic testing panels globally, finding inconsistent gene inclusion and potential diagnostic challenges.

Large-scale Analyses of CAV1 and CAV2 Suggest Their Expression is Higher in Post-mortem ALS Brain Tissue and Affects Survival

The paper analyzes CAV1 and CAV2 expression in ALS brain tissue and finds higher expression in ALS patients, associated with increased survival and slower disease progression.

A cell-penetrant peptide blocking C9ORF72-repeat RNA nuclear export suppresses neurodegeneration

This paper develops a cell-penetrant peptide that blocks C9ORF72-repeat RNA nuclear export, reducing neurodegeneration in preclinical models of ALS and FTD.

Mutations in the tail domain of the neurofilament heavy chain gene increase the risk of amyotrophic lateral sclerosis

This study identifies NEFH tail domain mutations as risk factors for ALS through meta-analysis and variant burden analysis in case-control studies and whole-genome sequencing data.

Low expression of EXOSC2 protects against clinical COVID-19 and impedes SARS-CoV-2 replication

The paper identifies reduced EXOSC2 expression as protective against SARS-CoV-2 infection and clinical COVID-19 by inhibiting viral replication and upregulating antiviral genes.

GLT8D1 mutations cause amyotrophic lateral sclerosis via disruption of neurotrophin signalling within membrane lipid rafts

This paper identifies GLT8D1 mutations as a cause of ALS by disrupting neurotrophin signaling in lipid rafts through reduced ganglioside expression.

Common and rare variant analyses combined with single-cell multiomics reveal cell-type-specific molecular mechanisms of COVID-19 severity

This study combines common and rare variant analyses with single-cell multiomics to identify cell-type-specific genetic risk factors for severe COVID-19, revealing molecular mechanisms and potential therapeutic targets.

Mitochondrial function determines severity but not risk of amyotrophic lateral sclerosis

The paper investigates how mitochondrial function affects ALS severity but not risk, identifying specific genetic and expression factors linked to disease progression.

Genome-wide Identification of the Genetic Basis of Amyotrophic Lateral Sclerosis

This study identifies 690 candidate ALS genes using a hierarchical Bayesian model, highlighting genetic convergence on the distal axon and functional significance in motor neurons.

Non-Coding Genetic Analysis Implicates Interleukin 18 Receptor Accessory Protein 3'UTR in Amyotrophic Lateral Sclerosis

The paper identifies non-coding variants in the IL18RAP 3'UTR that reduce ALS risk by modulating neuro-inflammation through NF-κB signaling in microglia.