Jeffrey P. Spence
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View article: Causal modelling of gene effects from regulators to programs to traits
Causal modelling of gene effects from regulators to programs to traits Open
Genetic association studies provide a unique tool for identifying candidate causal links from genes to human traits and diseases. However, it is challenging to determine the biological mechanisms underlying most associations, and we lack g…
View article: Specificity, length and luck drive gene rankings in association studies
Specificity, length and luck drive gene rankings in association studies Open
Standard genome-wide association studies (GWAS) and rare variant burden tests are essential tools for identifying trait-relevant genes 1 . Although these methods are conceptually similar, by analysing association studies of 209 quantitativ…
View article: Gene regulatory network structure informs the distribution of perturbation effects
Gene regulatory network structure informs the distribution of perturbation effects Open
Gene regulatory networks (GRNs) govern many core developmental and biological processes underlying human complex traits. Even with broad-scale efforts to characterize the effects of molecular perturbations and interpret gene coexpression, …
View article: Regulatory network topology and the genetic architecture of gene expression
Regulatory network topology and the genetic architecture of gene expression Open
In human populations, most of the genetic variance in gene expression can be attributed to trans -acting expression quantitative trait loci (eQTLs) spread across the genome. However, in practice it is difficult to discover these eQTLs, and…
View article: Predicting the effect of CRISPR-Cas9-based epigenome editing
Predicting the effect of CRISPR-Cas9-based epigenome editing Open
Epigenetic regulation orchestrates mammalian transcription, but functional links between them remain elusive. To tackle this problem, we use epigenomic and transcriptomic data from 13 ENCODE cell types to train machine learning models to p…
View article: Causal modeling of gene effects from regulators to programs to traits: integration of genetic associations and Perturb-seq
Causal modeling of gene effects from regulators to programs to traits: integration of genetic associations and Perturb-seq Open
Genetic association studies provide a unique tool for identifying causal links from genes to human traits and diseases. However, it is challenging to determine the biological mechanisms underlying most associations, and we lack genome-scal…
View article: Predicting the effect of CRISPR-Cas9-based epigenome editing
Predicting the effect of CRISPR-Cas9-based epigenome editing Open
Epigenetic regulation orchestrates mammalian transcription, but functional links between them remain elusive. To tackle this problem, we use epigenomic and transcriptomic data from 13 ENCODE cell types to train machine learning models to p…
View article: Characterizing selection on complex traits through conditional frequency spectra
Characterizing selection on complex traits through conditional frequency spectra Open
Natural selection on complex traits is difficult to study in part due to the ascertainment inherent to genome-wide association studies (GWAS). The power to detect a trait-associated variant in GWAS is a function of its frequency and effect…
View article: Specificity, length, and luck: How genes are prioritized by rare and common variant association studies
Specificity, length, and luck: How genes are prioritized by rare and common variant association studies Open
Standard genome-wide association studies (GWAS) and rare variant burden tests are essential tools for identifying trait-relevant genes. Although these methods are conceptually similar, we show by analyzing association studies of 209 quanti…
View article: Buffering and non-monotonic behavior of gene dosage response curves for human complex traits
Buffering and non-monotonic behavior of gene dosage response curves for human complex traits Open
The genome-wide burdens of deletions, loss-of-function mutations, and duplications correlate with many traits. Curiously, for most of these traits, variants that decrease expression have the same genome-wide average direction of effect as …
View article: Large future genetic diversity losses are predicted even with habitat protection
Large future genetic diversity losses are predicted even with habitat protection Open
Genetic diversity within species is the basis for evolutionary adaptive capacity and has recently been included as a target for protection in the United Nations’ Global Biodiversity Framework (GBF). However, we lack large-scale mathematica…
View article: Estimation of demography and mutation rates from one million haploid genomes
Estimation of demography and mutation rates from one million haploid genomes Open
As genetic sequencing costs have plummeted, datasets with sizes previously un-thinkable have begun to appear. Such datasets present new opportunities to learn about evolutionary history, particularly via rare alleles that record the very r…
View article: Pennsieve: A Collaborative Platform for Translational Neuroscience and Beyond
Pennsieve: A Collaborative Platform for Translational Neuroscience and Beyond Open
The exponential growth of neuroscientific data necessitates platforms that facilitate data management and multidisciplinary collaboration. In this paper, we introduce Pennsieve - an open-source, cloud-based scientific data management platf…
View article: Investigating the Role of Neighborhood Socioeconomic Status and Germline Genetics on Prostate Cancer Risk
Investigating the Role of Neighborhood Socioeconomic Status and Germline Genetics on Prostate Cancer Risk Open
Background Genetic factors play an important role in prostate cancer (PCa) development with polygenic risk scores (PRS) predicting disease risk across genetic ancestries. However, there are few convincing modifiable factors for PCa and lit…
View article: grenedalf: population genetic statistics for the next generation of pool sequencing
grenedalf: population genetic statistics for the next generation of pool sequencing Open
Summary Pool sequencing is an efficient method for capturing genome-wide allele frequencies from multiple individuals, with broad applications such as studying adaptation in Evolve-and-Resequence experiments, monitoring of genetic diversit…
View article: Haplotype Analysis Reveals Pleiotropic Disease Associations in the HLA Region
Haplotype Analysis Reveals Pleiotropic Disease Associations in the HLA Region Open
The human leukocyte antigen (HLA) region plays an important role in human health through involvement in immune cell recognition and maturation. While genetic variation in the HLA region is associated with many diseases, the pleiotropic pat…
View article: Gene regulatory network structure informs the distribution of perturbation effects
Gene regulatory network structure informs the distribution of perturbation effects Open
Gene regulatory networks (GRNs) govern many core developmental and biological processes underlying human complex traits. Even with broad-scale efforts to characterize the effects of molecular perturbations and interpret gene coexpression, …
View article: Conditional frequency spectra as a tool for studying selection on complex traits in biobanks
Conditional frequency spectra as a tool for studying selection on complex traits in biobanks Open
Natural selection on complex traits is difficult to study in part due to the ascertainment inherent to genome-wide association studies (GWAS). The power to detect a trait-associated variant in GWAS is a function of frequency and effect siz…
View article: A simple and flexible test of sample exchangeability with applications to statistical genomics
A simple and flexible test of sample exchangeability with applications to statistical genomics Open
In scientific studies involving analyses of multivariate data, basic but important questions often arise for the researcher: Is the sample exchangeable, meaning that the joint distribution of the sample is invariant to the ordering of the …
View article: Predicting the effect of CRISPR-Cas9-based epigenome editing
Predicting the effect of CRISPR-Cas9-based epigenome editing Open
Epigenetic regulation orchestrates mammalian transcription, but functional links between them remain elusive. To tackle this problem, we here use epigenomic and transcriptomic data from 13 ENCODE cell types to train machine learning models…
View article: Reviewer #2 (Public Review): Predicting the effect of CRISPR-Cas9-based epigenome editing
Reviewer #2 (Public Review): Predicting the effect of CRISPR-Cas9-based epigenome editing Open
Epigenetic regulation orchestrates mammalian transcription, but functional links between them remain elusive. To tackle this problem, we here use epigenomic and transcriptomic data from 13 ENCODE cell types to train machine learning models…
View article: Predicting the effect of CRISPR-Cas9-based epigenome editing
Predicting the effect of CRISPR-Cas9-based epigenome editing Open
Epigenetic regulation orchestrates mammalian transcription, but functional links between them remain elusive. To tackle this problem, we use epigenomic and transcriptomic data from 13 ENCODE cell types to train machine learning models to p…
View article: Reviewer #1 (Public Review): Predicting the effect of CRISPR-Cas9-based epigenome editing
Reviewer #1 (Public Review): Predicting the effect of CRISPR-Cas9-based epigenome editing Open
Epigenetic regulation orchestrates mammalian transcription, but functional links between them remain elusive. To tackle this problem, we here use epigenomic and transcriptomic data from 13 ENCODE cell types to train machine learning models…
View article: s_het estimates from GeneBayes and other supplementary datasets
s_het estimates from GeneBayes and other supplementary datasets Open
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