Hemali P. Phatnani

Dissecting cellular and molecular networks of aging and senescence in the human hippocampus

This study identifies spatially resolved aging and senescence signatures in the human hippocampus using multi-omics approaches, revealing cell-type and sex-specific gene expression changes.

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.

Multiscale harmonization, semantic integration, and immersive exploration of single-cell data in support of novel biological insights

A free Meta Quest virtual reality app harmonizes CODEX, Visium, Xenium, volumetric immunofluorescence and electron microscopy data from 5 organs into 4 scale levels using the Human Reference Atlas.

APOE-ϵ4-induced Fibronectin at the blood-brain barrier is a conserved pathological mediator of disrupted astrocyte-endothelia interaction in Alzheimer's disease

This paper identifies APOE-ϵ4-induced fibronectin accumulation at the blood-brain barrier as a key mediator of astrocyte-endothelial dysfunction in Alzheimer's disease, highlighting it as a potential therapeutic target.

Distinct Cellular Phenotypes of Language and Executive Decline in Amyotrophic Lateral Sclerosis

The paper maps cognitive impairments in ALS by integrating spatial and single-nucleus transcriptomics, revealing distinct cellular and molecular patterns in language and executive dysfunction.

A multi-omics characterization reveals distinct molecular signatures in the human motor cortex and lumbar spinal cord in ALS

This study uses multi-omics data to compare molecular signatures in the motor cortex and lumbar spinal cord of ALS patients, finding distinct alterations in MN and glial functions depending on symptom onset site.

TDP-43 dysfunction leads to the accumulation of cryptic transposable element-derived exons, crypTEs, in iPSC derived neurons and ALS/FTD patient tissues

This study identifies TDP-43-dependent cryptic gene-TE fusions (crypTEs) in neurons and ALS/FTD tissues, showing their association with altered gene expression and potential pathogenic effects.

Tissue and cellular spatiotemporal dynamics in colon aging

This study creates a spatial and cellular atlas of the colon across age groups using spatial transcriptomics and single nucleus RNA-seq, identifying age-related molecular gradients and multicellular programs.

Single-cell transcriptomic landscape of the neuroimmune compartment in amyotrophic lateral sclerosis brain and spinal cord

The paper identifies microglia subsets in ALS brain and spinal cord, finding an undifferentiated phenotype and enrichment of interferon response microglia in aggressive cases.

ALS molecular subtypes are a combination of cellular, genetic, and pathological features learned by deep multiomics classifiers

This study introduces DANcer, a deep learning classifier that identifies robust ALS molecular subtypes across bulk and single-cell datasets, showing they correlate with clinical features and cellular mechanisms.

Uncovering the Signatures of Cellular Senescence in the Human Dorsolateral Prefrontal Cortex

The paper identifies senescent cell signatures in the human dorsolateral prefrontal cortex using spatial transcriptomics and single nucleus RNA sequencing, revealing heterogeneity and cell-type-specific aging patterns.

Rare variant analyses validate known ALS genes in a multi-ethnic population and identifies ANTXR2 as a candidate in PLS

A Cellular Taxonomy of the Adult Human Spinal Cord

This paper presents a cellular taxonomy of the adult human spinal cord using single nucleus RNA-sequencing and spatial transcriptomics, identifying 29 glial and 35 neuronal clusters and highlighting motoneuron vulnerability to ALS.

A scalable screening platform for phenotypic subtyping of ALS patient-derived fibroblasts

The paper develops a scalable platform combining microscopy and machine learning to subtype ALS patient fibroblasts, identifying a FUS-ALS phenotypic score that correlates with age and treatment response.

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.

PySeq2500: An open source toolkit for repurposing HiSeq 2500 sequencing systems as versatile fluidics and imaging platforms.

PySeq2500 converts the HiSeq 2500 into an open platform for programmable fluidics and imaging, enabling automated multi-day workflows for multiplexed imaging of biological samples.

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.

Common ALS/FTD risk variants in UNC13A exacerbate its cryptic splicing and loss upon TDP-43 mislocalization

The paper shows that ALS/FTD risk variants in UNC13A increase sensitivity to TDP-43 depletion by promoting cryptic exon inclusion and protein loss.

Cell-type specific in vitro gene expression profiling of stem-cell derived neural models

The paper extends the RiboTag system for cell-type specific RNA depletion in vitro, showing variable efficiency across replicates.

Enrichment of rare protein truncating variants in amyotrophic lateral sclerosis patients

The paper identifies an enrichment of rare protein-truncating variants in ALS patients, highlighting novel genes like DNAJC7 and known ALS genes such as SOD1, NEK1, and FUS.

Postmortem Cortex Samples Identify Distinct Molecular Subtypes of ALS: Retrotransposon Activation, Oxidative Stress, and Activated Glia

The paper uses unsupervised machine learning to identify three molecular subtypes in ALS cortex samples, associated with oxidative stress, retrotransposon activation, and glial activation.

MetroNome - a visual data exploration platform for integrating human genotypic and phenotypic data across diseases

MetroNome integrates human genotypic and phenotypic data across diseases for hypothesis generation and analysis.

Splotch: Robust estimation of aligned spatial temporal gene expression data.

Splotch aligns spatial transcriptomics data across tissue sections and timepoints to improve gene expression estimates and study optimal experimental design.

Regional collapsing of rare variation implicates specific genic regions in ALS

The paper applies two novel collapsing methods to ALS sequencing data to identify risk regions in known ALS genes and candidate genes.

Spatiotemporal Dynamics of Molecular Pathology in Amyotrophic Lateral Sclerosis

Analysis of the ALS spinal cord using Spatial Transcriptomics reveals spatiotemporal dynamics of disease driven gene regulation.

Cell type-specific CLIP reveals that NOVA regulates cytoskeleton interactions in motoneurons

The paper develops a method to study cell-type specific RNA regulation in motoneurons and finds NOVA regulates cytoskeleton interactions by promoting a specific isoform of Septin 8.

An Efficient Platform For Astrocyte Differentiation From Human Induced Pluripotent Stem Cells

The paper describes a method to generate highly pure astrocytes from hiPSCs, showing they resemble primary astrocytes and have functional properties relevant to neurological disorders.