Noah Zaitlen

Epigenomic heterogeneity and spatial organization during human reprogramming

This study examines epigenomic and spatial changes during human reprogramming, finding distinct molecular and spatial patterns in productive versus unsuccessful trajectories.

Disentangling phenotype scale, amplification, and effect heterogeneity underlying polygenic GxE architecture of complex traits

This paper introduces REGENA, a method to disentangle gene-environment interaction mechanisms, finding that half of significant GxE signals are scale-dependent and effect heterogeneity drives most remaining GxE heritability.

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.

FastGxC: Fast and Powerful Context-Specific eQTL Mapping in Bulk and Single-Cell Data

FastGxC efficiently maps context-specific eQTLs in bulk and single-cell RNA-seq data, improving power and speed while enhancing biological relevance and trait association precision.

Advancing Precision Health Discovery in a Genetically Diverse Health System

The paper analyzes genetic and health record data from a diverse population to uncover gene-phenotype associations and assess polygenic score performance across ancestries.

SPC: a SPectral Component approach leveraging Identity-by-Descent graphs to address recent population structure in genomic analysis

SPC improves population structure adjustment in genomic analysis by capturing fine-scale patterns better than principal components, reducing p-value inflation and improving rare variant associations.

The relationship between genotype- and phenotype-based estimates of genetic liability to psychiatric disorders, in practice and in theory.

The paper shows genotype- and phenotype-based genetic instruments explain largely independent components of liability to psychiatric disorders, supported by theoretical analysis and simulations.

Cell-Type-Resolved Isoform Atlas of Human Tissues Reveals Age and Alzheimer's Disease-Associated Splicing Changes

The paper introduces Sciege, a method to estimate cell type-specific isoform distributions using bulk and single-cell RNA-seq data, revealing age and Alzheimer's disease-related splicing changes.

Comprehensive gene heritability estimation reveals the genetic architecture of rare coding variants underlying complex traits

This paper introduces FLEX, a method for estimating gene-level heritability from whole-exome sequencing data, showing rare coding variants contribute significantly to complex trait heritability.

Integrated ambient modeling and genetic demultiplexing of single-cell RNA+ATAC multiome experiments with Ambimux

The paper introduces ambimux, a method to estimate and demultiplex ambient molecule contamination in single-cell RNA+ATAC multiome data, improving the detection of biologically meaningful signals.

The geometry of G x E: how scaling and endogenous treatment effects shape interaction direction

This paper identifies how outcome scaling and endogenous treatment effects create spurious gene-environment interactions and proposes a diagnostic to detect these artifacts.

Investigating the sources of variable impact of pathogenic variants in monogenic metabolic conditions

The paper investigates why carriers of pathogenic variants in monogenic metabolic conditions show variable disease severity, finding support for variant effect sizes, polygenic backgrounds, and epistasis.

The impact of ambient contamination on demultiplexing methods for single-nucleus multiome experiments

The paper evaluates demultiplexing methods for joint snRNA/snATAC experiments under ambient contamination and introduces a new metric to assess their performance.

Characterizing the genetic architecture of drug response using gene-context interaction methods

This study quantifies the heritability of drug response to statins, metformin, warfarin, and methotrexate in UK Biobank participants and identifies genetic modifiers of drug effects and side effects.

Identifying novel genetic and phenotypic associations to genomic features by leveraging off-target reads in exome sequencing data

The paper uses unmapped reads from whole-exome sequencing data in the UK BioBank to construct features and identify 21 novel genetic loci associated with immune-related traits.

Simple models of non-random mating and environmental transmission bias standard human genetics statistical methods

The paper evaluates the impact of non-random mating and environmental transmission on genetic methods and introduces a simulation tool to improve robustness.

A scalable and robust variance components method reveals insights into the architecture of gene-environment interactions underlying complex traits

The paper introduces a variance components method to estimate gene-environment interaction heritability in complex traits using UK Biobank data, finding significant GxE effects for several trait-environment pairs.

Tissue informative cell-free DNA methylation sites in amyotrophic lateral sclerosis

The paper identifies tissue-informative DNA methylation sites in ALS using targeted sequencing and machine learning, showing accurate prediction of disease status and progression.

Deep Learning-based Phenotype Imputation on Population-scale Biobank Data Increases Genetic Discoveries

AutoComplete improves phenotype imputation in biobank data, enhancing GWAS power and genetic discovery.

A multivariate outcome test of covariance

The paper introduces MANOCCA, a method to test the effect of predictors on the covariance matrix of multivariate outcomes, showing it outperforms existing methods in simulations and identifies significant associations in real data.

A biobank-scale test of marginal epistasis reveals genome-wide signals of polygenic epistasis

The paper tests for polygenic epistasis in biobank-scale data and finds 16 trait-loci pairs with strong evidence of interaction effects.

PA-FGRS is a novel estimator of pedigree-based genetic liability that complements genotype-based inferences into the genetic architecture of major depressive disorder

The paper introduces PA-FGRS, a method to estimate genetic liability from family records, and shows it improves MDD classification and GWAS power when combined with genotypes.

Cell type deconvolution of bulk blood RNA-Seq to reveal biological insights of neuropsychiatric disorders

This study uses bulk RNA-Seq from blood samples to estimate cell type proportions and eQTLs, revealing cell-type specific genetic associations with psychiatric disorders and medication effects.

Phenotypic subtyping via contrastive learning

This paper introduces PACA, a contrastive learning method for subphenotype subtyping, which outperforms existing methods by capturing weak subphenotypic variation in complex diseases.

Cross-trait assortative mating is widespread and inflates genetic correlation estimates

This paper shows that cross-trait assortative mating explains genetic correlations between traits, suggesting many reported genetic similarities may be overestimated.

Multi-context genetic modeling of transcriptional regulation resolves novel disease loci

The paper introduces CONTENT, a method for multi-context genetic modeling of transcriptional regulation, which improves power and discovers more gene-phenotype associations in TWAS.

Leveraging genomic diversity for discovery in an EHR-linked biobank: the UCLA ATLAS Community Health Initiative

The paper explores the relationship between genomic ancestry and health outcomes using a biobank linked to electronic health records, finding disease stratification across ancestry clusters.

Methylation risk scores are associated with a collection of phenotypes within electronic health record systems

This study evaluates methylation risk scores (MRS) in clinical datasets, showing they improve EHR imputation and predict phenotypes better than polygenic risk scores or EHR-based methods alone.

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.

Massively Parallel Analysis of Human 3' UTRs Reveals that AU-Rich Element Length and Registration Predict mRNA Destabilization

The paper uses a massively parallel reporter assay to analyze 3' UTR sequences and shows that ARE length and registration affect mRNA stability and gene expression.