About

Fred Wright, Ph.D., is the Director of the Bioinformatics Research Center at North Carolina State University and holds the title of Goodnight Innovation Distinguished Professor of Statistics and Biological Sciences. He is based in 306 Ricks Hall and can be contacted via email at fred_wright@ncsu.edu. The page text does not provide further details about his specific research focus, background, or key contributions.

Research topics

• Biology
• Genetics
• Computational biology
• Pathology
• Medicine
• Computer Science
• Organic chemistry
• Geography
• Cell biology
• Engineering
• Environmental chemistry
• Ecology
• Gerontology
• Chemistry
• Library science
• Environmental science
• Biochemistry
• Evolutionary biology

Selected publications

• Genetic Modifiers of Cystic Fibrosis Lung Disease Severity: Whole-Genome Analysis of 7,840 Patients.

  UNC Libraries · 2025-10-22

  articleOpen access

  <strong>Rationale:</strong> Lung disease is the major cause of morbidity and mortality in persons with cystic fibrosis (pwCF). Variability in CF lung disease has substantial non-CFTR (CF transmembrane conductance regulator) genetic influence. Identification of genetic modifiers has prognostic and therapeutic importance. <strong>Objectives:</strong> Identify genetic modifier loci and genes/pathways associated with pulmonary disease severity. <strong>Methods:</strong> Whole-genome sequencing data on 4,248 unique pwCF with pancreatic insufficiency and lung function measures were combined with imputed genotypes from an additional 3,592 patients with pancreatic insufficiency from the United States, Canada, and France. This report describes association of approximately 15.9 million SNPs using the quantitative Kulich normal residual mortality-adjusted (KNoRMA) lung disease phenotype in 7,840 pwCF using premodulator lung function data. <strong>Measurements and Main Results:</strong> Testing included common and rare SNPs, transcriptome-wide association, gene-level, and pathway analyses. Pathway analyses identified novel associations with genes that have key roles in organ development, and we hypothesize that these genes may relate to dysanapsis and/or variability in lung repair. Results confirmed and extended previous genome-wide association study findings. These whole-genome sequencing data provide finely mapped genetic information to support mechanistic studies. No novel primary associations with common single variants or rare variants were found. Multilocus effects at chr5p13 (<em>SLC9A3/CEP72</em>) and chr11p13 (<em>EHF/APIP</em>) were identified. Variant effect size estimates at associated loci were consistently ordered across the cohorts, indicating possible age or birth cohort effects. <strong>Conclusions:</strong> This premodulator genomic, transcriptomic, and pathway association study of 7,840 pwCF will facilitate mechanistic and postmodulator genetic studies and the development of novel therapeutics for CF lung disease.

  PublisherDOI

• Signature gene expression model for quantitative evaluation of MASH-like liver injury in mice

  Toxicology and Applied Pharmacology · 2025-06-15 · 1 citations

  article
  PublisherDOI

• A workflow for human health hazard evaluation using transcriptomic data and Key Characteristics-based gene sets

  Toxicological Sciences · 2025-03-20 · 2 citations

  articleOpen access

  Key characteristics (KCs) are properties of chemicals that are associated with different types of human health hazards. KCs are used for systematic reviews in support of hazard identification. Transcriptomic data are a rich source of mechanistic data and are frequently interpreted through "enriched" pathways/gene sets. Such analyses may be challenging to interpret in regulatory science because of redundancy among pathways, complex data analyses, and unclear relevance to hazard identification. We hypothesized that by cross-mapping pathways/gene sets and KCs, the interpretability of transcriptomic data can be improved. We summarized 72 published KCs across 7 hazard traits into 34 umbrella KC terms. Gene sets from Reactome and Kyoto Encyclopedia of Genes and Genomes (KEGG) were mapped to these, resulting in "KC gene sets." These sets exhibit minimal overlap and vary in the number of genes. Comparisons of the same KC gene sets mapped from Reactome and KEGG revealed low similarity, indicating complementarity. Performance of these KC gene sets was tested using publicly available transcriptomic datasets of chemicals with known organ-specific toxicity: benzene and 2,3,7,8-tetrachlorodibenzo-p-dioxin tested in mouse liver and drugs sunitinib and amoxicillin tested in human-induced pluripotent stem cell-derived cardiomyocytes. We found that KC terms related to the mechanisms affected by tested compounds were highly enriched, while the negative control (amoxicillin) showed limited enrichment with marginal significance. This study's impact is in presenting a computational approach based on KCs for the analysis of toxicogenomic data and facilitating transparent interpretation of these data in the process of chemical hazard identification.

  PublisherOA PDFDOI

• Strain and Sex Variability in Liver, Kidney and Lung Levels of DNA Adducts EB-GII and &lt;em&gt;bis&lt;/em&gt;-N7G-BD Following Inhalation Exposure to 1,3-Butadiene in Collaborative Cross Mice

  Preprints.org · 2025-08-01

  preprintOpen access

  1,3-butadiene (BD) is a volatile organic pollutant. Upon inhalation, it is metabolically activated to reactive epoxides which alkylate genomic DNA and form potentially mu-tagenic monoadducts and DNA-DNA crosslinks including N7-(1-hydroxyl-3-buten-1-yl)guanine (EB-GII) and 1,4-bis-(guan-7-yl)-2,3-butanediol (bis-N7G-BD). While metabolic activation resulting in mutagenicity is a well-established mode of action for 1,3-butadiene, characterization of the extent of interindividual variability in response to BD exposure is a gap in our knowledge. Previous studies showed that population-wide mouse models can be used to evaluate variability in 1,3-butadiene DNA adducts; therefore, we hypothesized that this approach can be used to also study variability in formation and loss of BD-DNA adducts across tissues and between sexes. To test this hypothesis, female and male mice from genetically diverse 5 Collaborative Cross (CC) strains were exposed to filtered air or 1,3-butadiene (600 ppm, 6 h/day, 5 days/week for 2 weeks) by inhalation. Some animals were kept for 2 additional weeks after exposure to study DNA adduct persistence. EB-GII and bis-N7G-BD adducts were quantified in liver, lung and kidney using established isotope dilution ESI-MS/MS methods. We observed strain- and sex-specific ef-fects on both accumulation and loss of both adducts indicating that both factors play important roles in mutagenicity of 1,3-butadiene. In addition, we quantified the intra-species variability for each adduct and found that for most tissues/adducts, variability values across strains were modest compared to default uncertainty factors.

  PublisherOA PDFDOI

• Strain and Sex Variability in Liver, Kidney and Lung Levels of DNA Adducts EB-GII and bis-N7G-BD Following Inhalation Exposure to 1,3-Butadiene in Collaborative Cross Mice

  Toxics · 2025-10-03 · 1 citations

  articleOpen access

  1,3-butadiene (BD) is a volatile organic pollutant. Upon inhalation, it is metabolically activated to reactive epoxides which alkylate genomic DNA and form potentially mutagenic monoadducts and DNA–DNA crosslinks including N7-(1-hydroxyl-3-buten-1-yl)guanine (EB-GII) and 1,4-bis-(guan-7-yl)-2,3-butanediol (bis-N7G-BD). While metabolic activation resulting in mutagenicity is a well-established mode of action for 1,3-butadiene, characterization of the extent of inter-individual variability in response to BD exposure is a gap in our knowledge. Previous studies showed that population-wide mouse models can be used to evaluate variability in 1,3-butadiene DNA adducts; therefore, we hypothesized that this approach can be used to also study variability in the formation and loss of BD DNA adducts across tissues and between sexes. To test this hypothesis, female and male mice from five genetically diverse Collaborative Cross (CC) strains were exposed to filtered air or 1,3-butadiene (600 ppm, 6 h/day, 5 days/week for 2 weeks) by inhalation. Some animals were kept for two additional weeks after exposure to study DNA adduct persistence. EB-GII and bis-N7G-BD adducts were quantified in liver, lungs and kidney using established isotope dilution ESI-MS/MS methods. We observed strain- and sex-specific effects on both the accumulation and loss of both DNA adducts, indicating that both factors play important roles in the mutagenicity of 1,3-butadiene. In addition, we quantified the intra-species variability for each adduct and found that for most tissues/adducts, variability values across strains were modest compared to default uncertainty factors.

  PublisherOA PDFDOI

• Mediation analysis of the molecular phenotypes in a severe MASH-like liver injury mouse model

  Toxicological Sciences · 2025-08-08

  articleSenior author

  Metabolic dysfunction-associated steatohepatitis (MASH), a severe form of fatty liver disease, is a leading cause of cirrhosis and lacks effective therapies. Understanding the molecular mediators of disease progression remains a critical gap. This study aimed to investigate the roles of molecular phenotypes as mediators of MASH disease features in a diet-induced mouse model. Data used for these analyses were from a previous study where male and female CC042 mice were fed either a control or high-fat, high-sucrose (HF/HS) diet for 20, 40, or 60 weeks. Associations and mediated relationships between molecular and metabolic phenotypes and histopathologic markers of liver injury, inflammation, and lipid accumulation were assessed using regression modeling and causal mediation analyses. We observed strong associations between the HF/HS diet and duration of treatment and liver pathology, with a limited effect of sex. Mediation analysis revealed that liver lipid phenotypes, particularly monounsaturated and polyunsaturated fatty acids, consistently mediated the effects of diet on liver disease scores. Tumor necrosis factor alpha and C-X-C motif chemokine ligand 10, despite being treatment-induced, showed modest evidence of mediation on MASH or specific liver disease outcomes. Serum insulin showed modest mediation of inflammation and osmium staining, while serum glucose and triglycerides were not significant mediators. These findings highlight evidence that liver lipid metabolism may act as a primary mediator of MASH progression in this mouse model. The study underscores the value of mediation analysis for improved characterization of metabolic pathways in disease pathogenesis and supports the use of serum lipids as accessible biomarkers for clinical risk stratification and therapeutic targeting in MASH.

  PublisherDOI

• Exploring experiences of the regulatory toxicology system: system-level promoters and inhibitors of new approach methodologies

  Archives of Toxicology · 2025-09-09

  articleOpen access

  The transition from traditional animal-based approaches and assessments to New Approach Methodologies (NAMs) marks a scientific revolution in regulatory toxicology, with the potential of enhancing human and environmental protection. However, implementing the effective use of NAMs in regulatory toxicology has proven to be challenging, and so far, efforts to facilitate this change frequently focus on singular technical, psychological or economic inhibitors. This article takes a system-thinking approach to these challenges, a holistic framework for describing interactive relationships between the components of a system of interest. In this case, the regulatory toxicology system. We do so by analysing and interpreting a very large qualitative data set of experts' observations, collected in a 3-day interactive workshop and three follow-up online workshops with a heterogeneous sample of experts representing major actors from the global regulatory toxicology system. We identified leverage points (where a small change within a system can have a disproportionately large effect) in the six core aspects-infrastructure, processes, culture, technology, goals, and actors-in the regulatory toxicology system to facilitate the effective use of NAMs. Identified systematic leverage points include the need for a functioning incentive structure for effectively discovering, developing, validating and using NAMs within academia, regulation, and industry; and measures that prevent or mitigate unwanted effects of using NAMs that acknowledge clashes between scientific, regulatory, political and social processes. The results serve as a basis for follow-up activities that reflect on the actual effectiveness of these levers and that develop measures for the regulatory toxicology system.

  PublisherOA PDFDOI

• Genetic effects on chromatin accessibility uncover mechanisms of liver gene regulation and quantitative traits

  Genome Research · 2025-05-20 · 4 citations

  articleOpen access

  Chromatin accessibility quantitative trait locus (caQTL) studies have identified regulatory elements that underlie genetic effects on gene expression and metabolic traits. However, caQTL discovery has been limited by small sample sizes. Here, we map caQTLs in liver tissue from 138 human donors and identify caQTLs for 35,361 regulatory elements, including population-specific caQTLs driven by differences in allele frequency across populations. We identify 2126 genetic signals associated with multiple, presumably coordinately regulated elements. Coordinately regulated elements link distal elements to target genes and are more likely to be associated with gene expression compared with single-element caQTLs. We predict driver and response elements at coordinated loci and find that driver elements are enriched for transcription factor binding sites of key liver regulators. We identify colocalized caQTLs at 667 genome-wide association (GWAS) signals for metabolic and liver traits, and annotate these loci with predicted target genes and disrupted transcription factor binding sites. CaQTLs identify threefold more GWAS colocalizations than liver expression QTLs (eQTLs) in a larger sample size, suggesting that caQTLs can detect mechanisms missed by eQTLs. At a GWAS signal colocalized with a caQTL and an eQTL for TENM2 , we validated regulatory activity for a variant within a predicted driver element that is coordinately regulated with 39 other elements. At another locus, we validate a predicted enhancer of RALGPS2 using CRISPR interference and demonstrate allelic effects on transcription for a haplotype within this enhancer. These results demonstrate the power of caQTLs to characterize regulatory mechanisms at GWAS loci.

  PublisherOA PDFDOI

• Asian diversity in human immune cells

  Cell · 2025-03-19 · 51 citations

  articleOpen access

  The relationships of human diversity with biomedical phenotypes are pervasive yet remain understudied, particularly in a single-cell genomics context. Here, we present the Asian Immune Diversity Atlas (AIDA), a multi-national single-cell RNA sequencing (scRNA-seq) healthy reference atlas of human immune cells. AIDA comprises 1,265,624 circulating immune cells from 619 donors, spanning 7 population groups across 5 Asian countries, and 6 controls. Though population groups are frequently compared at the continental level, we found that sub-continental diversity, age, and sex pervasively impacted cellular and molecular properties of immune cells. These included differential abundance of cell neighborhoods as well as cell populations and genes relevant to disease risk, pathogenesis, and diagnostics. We discovered functional genetic variants influencing cell-type-specific gene expression, which were under-represented in non-Asian populations, and helped contextualize disease-associated variants. AIDA enables analyses of multi-ancestry disease datasets and facilitates the development of precision medicine efforts in Asia and beyond.

  PublisherDOI

• Liver eQTL meta-analysis illuminates potential molecular mechanisms of cardiometabolic traits

  UNC Libraries · 2025-02-02

  articleOpen access

  Understanding the molecular mechanisms of complex traits is essential for developing targeted interventions. We analyzed liver expression quantitative-trait locus (eQTL) meta-analysis data on 1,183 participants to identify conditionally distinct signals. We found 9,013 eQTL signals for 6,564 genes; 23% of eGenes had two signals, and 6% had three or more signals. We then integrated the eQTL results with data from 29 cardiometabolic genome-wide association study (GWAS) traits and identified 1,582 GWAS-eQTL colocalizations for 747 eGenes. Non-primary eQTL signals accounted for 17% of all colocalizations. Isolating signals by conditional analysis prior to coloc resulted in 37% more colocalizations than using marginal eQTL and GWAS data, highlighting the importance of signal isolation. Isolating signals also led to stronger evidence of colocalization: among 343 eQTL-GWAS signal pairs in multi-signal regions, analyses that isolated the signals of interest resulted in higher posterior probability of colocalization for 41% of tests. Leveraging allelic heterogeneity, we predicted causal effects of gene expression on liver traits for four genes. To predict functional variants and regulatory elements, we colocalized eQTL with liver chromatin accessibility QTL (caQTL) and found 391 colocalizations, including 73 with non-primary eQTL signals and 60 eQTL signals that colocalized with both a caQTL and a GWAS signal. Finally, we used publicly available massively parallel reporter assays in HepG2 to highlight 14 eQTL signals that include at least one expression-modulating variant. This multi-faceted approach to unraveling the genetic underpinnings of liver-related traits could lead to therapeutic development.

  PublisherDOI

Recent grants

• NIH Grant R01HG009125

  NIH · $791k · 2020

• Graduate Training in Bioinformatics

  NIH · $6.6M · 2000–2028

• NIH Grant R01MH101819

  NIH · $1.3M · 2017

• Genetic Etiology of Cancer Drug Response

  NIH · $4.0M · 2012–2023

• NIH Grant R01GM058934

  NIH · $743k · 2004

Frequent coauthors

• Ivan Rusyn

  Texas A&M University

  90 shared

• Yi‐Hui Zhou

  Yahoo (United Kingdom)

  64 shared

• Ralf Krahe

  The University of Texas MD Anderson Cancer Center

  63 shared

• Andrew B. Nobel

  47 shared

• Michael R. Knowles

  Lung Institute

  45 shared

• Weihsueh A. Chiu

  Texas A&M University

  42 shared

• Fei Zou

  Shandong University of Technology

  42 shared

• Bo Yuan

  Baylor Genetics

  41 shared

Labs

• NCSU Bioinformatics Research CenterPI

  Bioinformatics and Statistical Genetics

Awards & honors

• 2023 ASM Microbiome Data Prize