Dheeraj Malhotra
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View article: Single-nucleus and spatial transcriptomic profiling of human temporal cortex and white matter reveals key associations with AD pathology
Single-nucleus and spatial transcriptomic profiling of human temporal cortex and white matter reveals key associations with AD pathology Open
Alzheimer's disease, the leading cause of dementia in the elderly, is a neurodegenerative disorder that has been studied to uncover therapeutic pathways through its molecular and cellular hallmarks. Here, we present a comprehensive investi…
View article: Functional genomic dissection of MS risk loci reveals convergence of cis and trans gene regulatory mechanisms in microglia
Functional genomic dissection of MS risk loci reveals convergence of cis and trans gene regulatory mechanisms in microglia Open
Summary Neurological diseases (NDs) are a major source of unmet medical need, and translational insights have been hampered by complex underlying pathophysiologies and limitations of experimental models. Noncoding single nucleotide polymor…
View article: T-bet+ CXCR3+ B cells drive hyperreactive B-T cell interactions in multiple sclerosis
T-bet+ CXCR3+ B cells drive hyperreactive B-T cell interactions in multiple sclerosis Open
Multiple sclerosis (MS) is an autoimmune disease of the central nervous system (CNS). Self-peptide-dependent autoproliferation (AP) of B and T cells is a key mechanism in MS. Here, we show that pro-inflammatory B-T cell-enriched cell clust…
View article: Cell state-dependent allelic effects and contextual Mendelian randomization analysis for human brain phenotypes
Cell state-dependent allelic effects and contextual Mendelian randomization analysis for human brain phenotypes Open
Gene expression quantitative trait loci are widely used to infer relationships between genes and central nervous system (CNS) phenotypes; however, the effect of brain disease on these inferences is unclear. Using 2,348,438 single-nuclei pr…
View article: snRNA-seq stratifies multiple sclerosis patients into distinct white matter glial responses
snRNA-seq stratifies multiple sclerosis patients into distinct white matter glial responses Open
Poor understanding of the cellular and molecular basis of clinical and genetic heterogeneity in progressive multiple sclerosis (MS) has hindered the search for new effective therapies. To address this gap, we analyzed 632,000 single-nucleu…
View article: Single-nucleus and spatial transcriptomic profiling of human temporal cortex and white matter reveals novel associations with AD pathology
Single-nucleus and spatial transcriptomic profiling of human temporal cortex and white matter reveals novel associations with AD pathology Open
Alzheimer’s disease (AD) is a neurodegenerative disorder with complex pathological manifestations and is the leading cause of cognitive decline and dementia in elderly individuals. A major goal in AD research is to identify new therapeutic…
View article: Data Mining: Applications and Trends
Data Mining: Applications and Trends Open
View article: Disease-specific selective vulnerability and neuroimmune pathways in dementia revealed by single cell genomics
Disease-specific selective vulnerability and neuroimmune pathways in dementia revealed by single cell genomics Open
Summary/Abstract The development of successful therapeutics for dementias requires an understanding of their shared and distinct molecular features in the human brain. We performed single-nuclear RNAseq and ATACseq in Alzheimer disease (AD…
View article: Schizophrenia-associated somatic copy-number variants from 12,834 cases reveal recurrent NRXN1 and ABCB11 disruptions
Schizophrenia-associated somatic copy-number variants from 12,834 cases reveal recurrent NRXN1 and ABCB11 disruptions Open
While germline copy-number variants (CNVs) contribute to schizophrenia (SCZ) risk, the contribution of somatic CNVs (sCNVs)-present in some but not all cells-remains unknown. We identified sCNVs using blood-derived genotype arrays from 12,…
View article: A structured evaluation of cryopreservation in generating single-cell transcriptomes from cerebrospinal fluid
A structured evaluation of cryopreservation in generating single-cell transcriptomes from cerebrospinal fluid Open
Single-cell transcriptomics allows characterization of cerebrospinal fluid (CSF) cells at an unprecedented level. Here, we report a robust cryopreservation protocol adapted for the characterization of fragile CSF cells by single-cell RNA s…
View article: Author Correction: Protein interaction network of alternatively spliced isoforms from brain links genetic risk factors for autism
Author Correction: Protein interaction network of alternatively spliced isoforms from brain links genetic risk factors for autism Open
View article: Single-cell Mendelian randomisation identifies cell-type specific genetic effects on human brain disease and behaviour
Single-cell Mendelian randomisation identifies cell-type specific genetic effects on human brain disease and behaviour Open
Translating genome-wide association loci to therapies requires knowledge of the causal genes, their directionality of effect and the cell-types in which they act. To infer these relationships in the human brain, we implemented Mendelian ra…
View article: Analysis of the caudate nucleus transcriptome in individuals with schizophrenia highlights effects of antipsychotics and new risk genes
Analysis of the caudate nucleus transcriptome in individuals with schizophrenia highlights effects of antipsychotics and new risk genes Open
View article: Cell-type-specific cis-eQTLs in eight human brain cell types identify novel risk genes for psychiatric and neurological disorders
Cell-type-specific cis-eQTLs in eight human brain cell types identify novel risk genes for psychiatric and neurological disorders Open
View article: Single nuclei RNAseq stratifies multiple sclerosis patients into distinct white matter glial responses
Single nuclei RNAseq stratifies multiple sclerosis patients into distinct white matter glial responses Open
The lack of understanding of the cellular and molecular basis of clinical and genetic heterogeneity in progressive multiple sclerosis (MS) has hindered the search for new effective therapies. Here, to address this gap, we analysed 632,000 …
View article: Epigenomic priming of immune genes implicates oligodendroglia in multiple sclerosis susceptibility
Epigenomic priming of immune genes implicates oligodendroglia in multiple sclerosis susceptibility Open
View article: Rare schizophrenia risk variant burden is conserved in diverse human populations
Rare schizophrenia risk variant burden is conserved in diverse human populations Open
Schizophrenia is a chronic mental illness that is amongst the most debilitating conditions encountered in medical practice. A recent landmark schizophrenia study of the protein-coding regions of the genome identified a causal role for ten …
View article: Defining the architecture of cerebrospinal fluid cellular communities in neuroinflammatory diseases
Defining the architecture of cerebrospinal fluid cellular communities in neuroinflammatory diseases Open
Cerebrospinal fluid (CSF) biomarkers are important for multiple sclerosis (MS) diagnosis. Moreover, absent of autopsy or biopsy tissue, CSF is the most relevant source for studying the immune cells involved in MS pathophysiology. Single-ce…
View article: Cell-type specific cis-eQTLs in eight brain cell-types identifies novel risk genes for human brain disorders
Cell-type specific cis-eQTLs in eight brain cell-types identifies novel risk genes for human brain disorders Open
Most expression quantitative trait loci (eQTL) studies to date have been performed in heterogeneous brain tissues as opposed to specific cell types. To investigate the genetics of gene expression in adult human cell types from the central …
View article: A structured evaluation of cryopreservation in generating single cell transcriptomes from cerebrospinal fluid
A structured evaluation of cryopreservation in generating single cell transcriptomes from cerebrospinal fluid Open
Importance A robust cerebrospinal fluid (CSF) cell cryopreservation protocol using high resolution single-cell (sc) transcriptomic data would enable the deployment of this important modality in multi-center translational research studies a…
View article: CellMixS: quantifying and visualizing batch effects in single-cell RNA-seq data
CellMixS: quantifying and visualizing batch effects in single-cell RNA-seq data Open
A key challenge in single-cell RNA-sequencing (scRNA-seq) data analysis is batch effects that can obscure the biological signal of interest. Although there are various tools and methods to correct for batch effects, their performance can v…
View article: A Structured Evaluation of Cryopreservation in Generating Single Cell Transcriptomes From Cerebrospinal Fluid
A Structured Evaluation of Cryopreservation in Generating Single Cell Transcriptomes From Cerebrospinal Fluid Open
View article: CellMixS: quantifying and visualizing batch effects in single cell RNA-seq data
CellMixS: quantifying and visualizing batch effects in single cell RNA-seq data Open
A key challenge in single cell RNA-sequencing (scRNA-seq) data analysis are dataset- and batch-specific differences that can obscure the biological signal of interest. While there are various tools and methods to perform data integration a…
View article: muscat detects subpopulation-specific state transitions from multi-sample multi-condition single-cell transcriptomics data
muscat detects subpopulation-specific state transitions from multi-sample multi-condition single-cell transcriptomics data Open
View article: Tau Pathology Drives Dementia Risk-Associated Gene Networks toward Chronic Inflammatory States and Immunosuppression
Tau Pathology Drives Dementia Risk-Associated Gene Networks toward Chronic Inflammatory States and Immunosuppression Open
To understand how neural-immune-associated genes and pathways contribute to neurodegenerative disease pathophysiology, we performed a systematic functional genomic analysis in purified microglia and bulk tissue from mouse and human AD, FTD…
View article: Translating genome-wide association findings into new therapeutics for psychiatry
Translating genome-wide association findings into new therapeutics for psychiatry Open
Genome-wide association studies (GWAS) in psychiatry, once they reach sufficient sample size and power, have been enormously successful. The Psychiatric Genomics Consortium (PGC) aims for mega-analyses with sample sizes that will grow to (…
View article: Contribution of copy number variants to schizophrenia from a genome-wide study of 41,321 subjects
Contribution of copy number variants to schizophrenia from a genome-wide study of 41,321 subjects Open
Copy number variants (CNVs) have been strongly implicated in the genetic etiology of schizophrenia (SCZ). However, genome-wide investigation of the contribution of CNV to risk has been hampered by limited sample sizes. We sought to address…
View article: On the discovery of subpopulation-specific state transitions from multi-sample multi-condition single-cell RNA sequencing data
On the discovery of subpopulation-specific state transitions from multi-sample multi-condition single-cell RNA sequencing data Open
Single-cell RNA sequencing (scRNA-seq) has quickly become an empowering technology to profile the transcriptomes of individual cells on a large scale. Many early analyses of differential expression have aimed at identifying differences bet…
View article: Targeted Treatment of Individuals With Psychosis Carrying a Copy Number Variant Containing a Genomic Triplication of the Glycine Decarboxylase Gene
Targeted Treatment of Individuals With Psychosis Carrying a Copy Number Variant Containing a Genomic Triplication of the Glycine Decarboxylase Gene Open
View article: Altered human oligodendrocyte heterogeneity in multiple sclerosis
Altered human oligodendrocyte heterogeneity in multiple sclerosis Open