Towfique Raj

Parkinson's disease genetic risk converges on Lewy body pathology-associated microglial states

The paper identifies microglial states associated with Parkinson's disease genetic risk and Lewy body pathology using single-cell profiling and integrates data with AMP PD.

Exploring transcriptomic and genomic latent variable correction approaches in differential expression analysis.

This paper evaluates combining expression-based surrogate variables and genotype-based principal components in differential expression analysis, finding the combined approach improves replicability and biological recall in ALS datasets.

Peripheral Immune Alterations and T Cell Clonal Dynamics Across the Parkinson's Disease Spectrum

This study uses single-cell RNA sequencing and TCR profiling to analyze immune changes in Parkinson's disease across different stages and identifies sex-dependent immune alterations and TCR diversity.

Genetic and epigenetic convergence at MOBP links ALS and PSP

The paper identifies shared genetic and epigenetic mechanisms at the MOBP locus linking ALS and PSP, with distinct patterns from MSA.

LRRK2 G2019S variant is associated with transcriptional changes in Parkinson's disease human myeloid cells under proinflammatory environment

This study shows the G2019S LRRK2 mutation alters transcriptomes of myeloid cells under proinflammatory conditions, affecting lipid metabolism and phagocytic function.

An empirical Bayes framework for burden and dispersion association tests helps prioritize rare variants associated with Alzheimer's disease

The paper introduces parmigiano, an empirical Bayesian framework that improves rare variant association testing in Alzheimer's disease by integrating functional annotations, identifying 23 candidate genes including 19 new ones.

A TAD-informed aging-brain xQTL atlas of multi-modal and cell-type-resolved regulatory variation

The paper presents an xQTL atlas of regulatory variation in the aging human brain, integrating multiple modalities and cell types across four studies, identifying more variant-molecular-trait associations by including TAD boundaries.

Single-nucleus epigenomic dysregulation unmasks genetic risk-associated neurodegenerative glia states

The paper identifies glial cell-specific regulatory elements and genetic risk modifiers in tau-related dementias using single-nucleus epigenomic profiling.

SingleBrain: A Meta-Analysis of Single-Nucleus eQTLs Linking Genetic Risk to Brain Disorders

SingleBrain integrates snRNA-seq and genotype data to map cis-eQTLs across brain cell types, identifying novel disease-associated genes and causal variants.

Machine Learning-Based Prediction of Cell-type Resolved Brain eQTLs Enhances Discovery of Variants Explaining Alzheimer's Disease Heritability

The paper develops scEEMS models to predict cell-type-specific eQTLs, enhancing discovery of AD risk variants by linking them to cell-type-specific genes.

Regulatory landscape of Alzheimer's disease variants in human microglia

The paper identifies regulatory variants associated with Alzheimer's disease in human microglia using MPRA and highlights differences in variant activity between cell sources.

Integrated Stress Response Signatures Drive Monocyte Dysfunction in GBA1- and LRRK2-Linked Parkinson's Disease

The paper identifies integrated stress response (ISR) signatures and proteostasis defects in monocytes from GBA1- and LRRK2-linked Parkinson's disease, linking them to immune dysfunction.

Meta-analysis of genetic regulation of RNA editing in the human brain identifies new genes underlying neurological disease

The paper identifies 38,731 edQTLs in 3,554 genes through a meta-analysis of A-to-I RNA editing in the human brain and links 24 GWAS loci for neurological disorders to edQTLs.

Mapping genetic effects on splicing in ten thousand post-mortem brain samples reveals novel mediators of neurological disease risk

The paper maps genetic effects on splicing in 10,725 brain samples, identifying 68,358 cis-sQTLs and 97 loci where splicing mediates neurological disease risk.

APOE4 promotes cerebrovascular fibrosis and amyloid deposition via a pericyte-to-myofibroblast transition

This study identifies APOE4-driven pericyte-to-myofibroblast transition in cerebrovascular disease, leading to fibrosis and amyloid deposition, and shows TGF-β inhibition can reverse these effects.

The human microglia responsome: a resource to better understand microglia states in health and disease

The paper characterizes the human microglia responsome by analyzing gene expression in microglia exposed to various stimuli, identifying distinct responses and genetic interactions relevant to disease.

DNA methylation as a contributor to dysregulation of STX6 and other frontotemporal lobar degeneration genetic risk-associated loci

The paper investigates DNA methylation changes in FTLD risk genes across different subtypes and finds shared hypomethylation in STX6 and other loci, with significant effects in PSP cases.

Mosaic chromosomal alterations in blood are associated with an increased risk of Alzheimer's disease

The paper finds that mosaic chromosomal alterations in blood are associated with increased Alzheimer's disease risk, with variations by ancestry, mCA subtype, APOE ε4 status, and chromosomal location.

Cytosine-to-uracil RNA editing is upregulated by pro-inflammatory stimulation of myeloid cells

The paper analyzes RNA editing in myeloid cells under inflammatory stimulation, finding that C-to-U editing has a larger effect on proteome recoding compared to A-to-I editing.

Integration of Deep Learning Annotations with Functional Genomics Improves Identification of Causal Alzheimers Disease Variants

This paper improves identification of causal Alzheimer's disease variants by integrating deep learning annotations with functional genomics, resulting in better fine-mapping and polygenic risk prediction across diverse populations.

Long-read RNA-seq atlas of novel microglia isoforms elucidates disease-associated genetic regulation of splicing

The paper presents a long-read RNA-seq atlas of microglia isoforms, identifying novel isoforms and their associations with genetic risk loci in Alzheimer's and Parkinson's disease.

Leveraging functional annotations to map rare variants associated with Alzheimer's disease with gruyere

This study introduces gruyere, a Bayesian model that improves rare variant association analysis by integrating functional annotations, identifying 15 new AD-associated genetic associations.

Genetic, transcriptomic, histological, and biochemical analysis of progressive supranuclear palsy implicates glial activation and novel risk genes

This study identifies six genetic loci associated with progressive supranuclear palsy, including a novel locus, and links them to oligodendrocytic dysfunction and C4A expression.

TDP-43 loss induces extensive cryptic polyadenylation in ALS/FTD

The paper identifies novel cryptic polyadenylation events induced by TDP-43 loss in ALS/FTD using bioinformatic methods and shows their potential disease relevance and impact on protein translation.

Brain DNA methylomic analysis of frontotemporal lobar degeneration reveals OTUD4 in shared dysregulated signatures across pathological subtypes

This study identifies DNA methylation changes in FTLD subtypes, finding OTUD4 as a key gene with consistent expression dysregulation across subtypes.

APOE genotype or presence of brain amyloid alters the plasma proteome in cognitively normal, elderly subjects

The paper examines how APOE genotype and brain amyloid presence affect plasma proteome composition in cognitively normal elderly individuals, identifying associated molecular pathways.

Transcriptome deregulation of peripheral monocytes in GBA-related Parkinson's disease

The paper identifies transcriptomic changes in monocytes from GBA mutation carriers with Parkinson's disease, highlighting dysregulated pathways related to alpha-synuclein degradation and lysosomal function.

Genetics of the human microglia regulome refines Alzheimer's disease risk loci

The paper identifies regulatory mechanisms for 21 Alzheimer's disease risk loci in human microglia using transcriptome and chromatin accessibility profiling.

17q21.31 sub-haplotypes underlying H1-associated risk for Parkinsons disease are associated with LRRC37A/2 expression in astrocytes

The paper identifies three H1 sub-haplotypes at the 17q21.31 locus associated with Parkinson's disease risk and links them to LRRC37A/2 expression in astrocytes.

Cell environment shapes TDP-43 function: implications in neuronal and muscle disease

The paper compares TDP-43's transcriptional and splicing effects in muscle and neuronal cells, showing tissue-specific roles in disease.