Scholars@Duke
Joshua Aaron Granek

Joshua Aaron Granek

Assistant Professor in Biostatistics & Bioinformatics
Biostatistics & Bioinformatics, Division of Integrative Genomics
joshua.granek@duke.edu
Box 2721, 10044 Hock Plaza, Durham, NC 27710
2424 Erwin Rd,, 10044 Hock Plaza, Durham, NC 27710
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Selected Publications

Soil exposure modulates the immune response to an influenza challenge in a mouse model.

Journal Article Sci Total Environ · April 20, 2024 There is increasing evidence that early life microbial exposure aids in immune system maturation, more recently known as the "old friends" hypothesis. To test this hypothesis, 4-week-old mice were exposed to soils of increasing microbial diversity for four ... Full text Link to item Cite

Conjugation of HIV-1 envelope to hepatitis B surface antigen alters vaccine responses in rhesus macaques.

Journal Article NPJ Vaccines · November 24, 2023 An effective HIV-1 vaccine remains a critical unmet need for ending the AIDS epidemic. Vaccine trials conducted to date have suggested the need to increase the durability and functionality of vaccine-elicited antibodies to improve efficacy. We hypothesized ... Full text Open Access Link to item Cite

Advances in Graduate Training in Integrative Bioinformatics for Investigating and Engineering Microbiomes (IBIEM)

Conference ASEE Annual Conference and Exposition, Conference Proceedings · June 25, 2023 Innovations by engineers and physical scientists working at the frontiers of microbiome engineering and discovery requires in-depth understanding of microbiome systems with parallel skills in bioinformatics and biostatistics. Despite the importance of inte ... Cite

Cryptococcus neoformans Mar1 function links mitochondrial metabolism, oxidative stress, and antifungal tolerance.

Journal Article Front Physiol · 2023 Introduction: Microbial pathogens undergo significant physiological changes during interactions with the infected host, including alterations in metabolism and cell architecture. The Cryptococcus neoformans Mar1 protein is required for the proper ordering ... Full text Link to item Cite

Leveraging patient derived models of FGFR2 fusion positive intrahepatic cholangiocarcinoma to identify synergistic therapies.

Journal Article NPJ Precis Oncol · October 23, 2022 Intrahepatic cholangiocarcinoma (ICC) remains a deadly malignancy lacking systemic therapies for advanced disease. Recent advancements include selective FGFR1-3 inhibitors for the 15% of ICC patients harboring fusions, although survival is limited by poor ... Full text Link to item Cite

A Course in Biology and Communication Skills for Master of Biostatistics Students

Journal Article Journal of Curriculum and Teaching · January 1, 2022 We describe an innovative, semester-long course in biology and communication skills for master’s degree students in biostatistics. The primary goal of the course is to make the connection between biological science and statistics more explicit. The seconda ... Full text Cite

Comparative analysis of RNA enrichment methods for preparation of Cryptococcus neoformans RNA sequencing libraries.

Journal Article G3 (Bethesda) · October 19, 2021 RNA sequencing (RNA-Seq) experiments focused on gene expression involve removal of ribosomal RNA (rRNA) because it is the major RNA constituent of cells. This process, called RNA enrichment, is done primarily to reduce cost: without rRNA removal, deeper se ... Full text Link to item Cite

The Pediatric Obesity Microbiome and Metabolism Study (POMMS): Methods, Baseline Data, and Early Insights.

Journal Article Obesity (Silver Spring) · March 2021 OBJECTIVE: The purpose of this study was to establish a biorepository of clinical, metabolomic, and microbiome samples from adolescents with obesity as they undergo lifestyle modification. METHODS: A total of 223 adolescents aged 10 to 18 years with BMI ≥9 ... Full text Open Access Link to item Cite

Comparative analysis of RNA enrichment methods for preparation ofCryptococcus neoformansRNA sequencing libraries

Journal Article · 2021 ABSTRACT Ribosomal RNA (rRNA) is the major RNA constituent of cells, therefore most RNA sequencing (RNA-Seq) experiments involve removal of rRNA. This process, called RNA enrichment, is done primarily to reduce cost: without rRNA removal, deeper s ... Full text Cite

Nasal Immunization With Small Molecule Mast Cell Activators Enhance Immunity to Co-Administered Subunit Immunogens.

Journal Article Front Immunol · 2021 Mast cell activators are a novel class of mucosal vaccine adjuvants. The polymeric compound, Compound 48/80 (C48/80), and cationic peptide, Mastoparan 7 (M7) are mast cell activators that provide adjuvant activity when administered by the nasal route. Howe ... Full text Link to item Cite

The Pediatric Obesity Microbiome and Metabolism Study (POMMS): Methods, Baseline Data, and Early Insights

Journal Article · 2020 ABSTRACTObjective To establish a biorepository of clinical, metabolomic, and microbiome samples from adolescents with obesity as they undergo lifestyle modification. Methods We enrolled 223 adolescents aged 10-18 years with Body ... Full text Cite

A comparative study of gut microbiomes in captive nocturnal strepsirrhines.

Journal Article Am J Primatol · October 2019 Feeding strategy and diet are increasingly recognized for their roles in governing primate gut microbiome (GMB) composition. Whereas feeding strategy reflects evolutionary adaptations to a host's environment, diet is a more proximate measure of food intake ... Full text Link to item Cite

The effect of levofloxacin on the lung microbiota of laboratory rats.

Journal Article Exp Lung Res · September 2019 Aim: The aim of this study was to investigate the short-term effect of levofloxacin on the microbiota of healthy lungs. Material and methods: Male F344 rats received either no levofloxacin (n = 9), intravenous levofloxacin (n = 12), oral levofloxacin (n =  ... Full text Link to item Cite

bcSeq: an R package for fast sequence mapping in high-throughput shRNA and CRISPR screens.

Journal Article Bioinformatics · October 15, 2018 SUMMARY: CRISPR-Cas9 and shRNA high-throughput sequencing screens have abundant applications for basic and translational research. Methods and tools for the analysis of these screens must properly account for sequencing error, resolve ambiguous mappings am ... Full text Link to item Cite

Effect of gastric fluid aspiration on the lung microbiota of laboratory rats.

Journal Article Exp Lung Res · 2018 AIM OF THE STUDY: The pulmonary microbiota is important for both normal homeostasis and the progression of disease, and may be affected by aspiration of gastric fluid. The aim of this study was to investigate changes in the lung microbiota induced by aspir ... Full text Link to item Cite

Fungal genome and mating system transitions facilitated by chromosomal translocations involving intercentromeric recombination.

Journal Article PLoS Biol · August 2017 Species within the human pathogenic Cryptococcus species complex are major threats to public health, causing approximately 1 million annual infections globally. Cryptococcus amylolentus is the most closely known related species of the pathogenic Cryptococc ... Full text Link to item Cite

Elucidation of the calcineurin-Crz1 stress response transcriptional network in the human fungal pathogen Cryptococcus neoformans.

Journal Article PLoS Genet · April 2017 Calcineurin is a highly conserved Ca2+/calmodulin-dependent serine/threonine-specific protein phosphatase that orchestrates cellular Ca2+ signaling responses. In Cryptococcus neoformans, calcineurin is activated by multiple stresses including high temperat ... Full text Link to item Cite

Rapid mapping of insertional mutations to probe cell wall regulation in Cryptococcus neoformans.

Journal Article Fungal Genet Biol · September 2015 Random insertional mutagenesis screens are important tools in microbial genetics studies. Investigators in fungal systems have used the plant pathogen Agrobacterium tumefaciens to create tagged, random mutations for genetic screens in their fungal species ... Full text Link to item Cite

Integrating chemical mutagenesis and whole-genome sequencing as a platform for forward and reverse genetic analysis of Chlamydia.

Journal Article Cell Host Microbe · May 13, 2015 Gene inactivation by transposon insertion or allelic exchange is a powerful approach to probe gene function. Unfortunately, many microbes, including Chlamydia, are not amenable to routine molecular genetic manipulations. Here we describe an arrayed library ... Full text Link to item Cite

Soil exposure modulates the immune response to an influenza challenge in a mouse model.

Journal Article Sci Total Environ · April 20, 2024 There is increasing evidence that early life microbial exposure aids in immune system maturation, more recently known as the "old friends" hypothesis. To test this hypothesis, 4-week-old mice were exposed to soils of increasing microbial diversity for four ... Full text Link to item Cite

Conjugation of HIV-1 envelope to hepatitis B surface antigen alters vaccine responses in rhesus macaques.

Journal Article NPJ Vaccines · November 24, 2023 An effective HIV-1 vaccine remains a critical unmet need for ending the AIDS epidemic. Vaccine trials conducted to date have suggested the need to increase the durability and functionality of vaccine-elicited antibodies to improve efficacy. We hypothesized ... Full text Open Access Link to item Cite

Advances in Graduate Training in Integrative Bioinformatics for Investigating and Engineering Microbiomes (IBIEM)

Conference ASEE Annual Conference and Exposition, Conference Proceedings · June 25, 2023 Innovations by engineers and physical scientists working at the frontiers of microbiome engineering and discovery requires in-depth understanding of microbiome systems with parallel skills in bioinformatics and biostatistics. Despite the importance of inte ... Cite

Cryptococcus neoformans Mar1 function links mitochondrial metabolism, oxidative stress, and antifungal tolerance.

Journal Article Front Physiol · 2023 Introduction: Microbial pathogens undergo significant physiological changes during interactions with the infected host, including alterations in metabolism and cell architecture. The Cryptococcus neoformans Mar1 protein is required for the proper ordering ... Full text Link to item Cite

Leveraging patient derived models of FGFR2 fusion positive intrahepatic cholangiocarcinoma to identify synergistic therapies.

Journal Article NPJ Precis Oncol · October 23, 2022 Intrahepatic cholangiocarcinoma (ICC) remains a deadly malignancy lacking systemic therapies for advanced disease. Recent advancements include selective FGFR1-3 inhibitors for the 15% of ICC patients harboring fusions, although survival is limited by poor ... Full text Link to item Cite

A Course in Biology and Communication Skills for Master of Biostatistics Students

Journal Article Journal of Curriculum and Teaching · January 1, 2022 We describe an innovative, semester-long course in biology and communication skills for master’s degree students in biostatistics. The primary goal of the course is to make the connection between biological science and statistics more explicit. The seconda ... Full text Cite

Comparative analysis of RNA enrichment methods for preparation of Cryptococcus neoformans RNA sequencing libraries.

Journal Article G3 (Bethesda) · October 19, 2021 RNA sequencing (RNA-Seq) experiments focused on gene expression involve removal of ribosomal RNA (rRNA) because it is the major RNA constituent of cells. This process, called RNA enrichment, is done primarily to reduce cost: without rRNA removal, deeper se ... Full text Link to item Cite

The Pediatric Obesity Microbiome and Metabolism Study (POMMS): Methods, Baseline Data, and Early Insights.

Journal Article Obesity (Silver Spring) · March 2021 OBJECTIVE: The purpose of this study was to establish a biorepository of clinical, metabolomic, and microbiome samples from adolescents with obesity as they undergo lifestyle modification. METHODS: A total of 223 adolescents aged 10 to 18 years with BMI ≥9 ... Full text Open Access Link to item Cite

Comparative analysis of RNA enrichment methods for preparation ofCryptococcus neoformansRNA sequencing libraries

Journal Article · 2021 ABSTRACT Ribosomal RNA (rRNA) is the major RNA constituent of cells, therefore most RNA sequencing (RNA-Seq) experiments involve removal of rRNA. This process, called RNA enrichment, is done primarily to reduce cost: without rRNA removal, deeper s ... Full text Cite

Nasal Immunization With Small Molecule Mast Cell Activators Enhance Immunity to Co-Administered Subunit Immunogens.

Journal Article Front Immunol · 2021 Mast cell activators are a novel class of mucosal vaccine adjuvants. The polymeric compound, Compound 48/80 (C48/80), and cationic peptide, Mastoparan 7 (M7) are mast cell activators that provide adjuvant activity when administered by the nasal route. Howe ... Full text Link to item Cite

The Pediatric Obesity Microbiome and Metabolism Study (POMMS): Methods, Baseline Data, and Early Insights

Journal Article · 2020 ABSTRACTObjective To establish a biorepository of clinical, metabolomic, and microbiome samples from adolescents with obesity as they undergo lifestyle modification. Methods We enrolled 223 adolescents aged 10-18 years with Body ... Full text Cite

A comparative study of gut microbiomes in captive nocturnal strepsirrhines.

Journal Article Am J Primatol · October 2019 Feeding strategy and diet are increasingly recognized for their roles in governing primate gut microbiome (GMB) composition. Whereas feeding strategy reflects evolutionary adaptations to a host's environment, diet is a more proximate measure of food intake ... Full text Link to item Cite

The effect of levofloxacin on the lung microbiota of laboratory rats.

Journal Article Exp Lung Res · September 2019 Aim: The aim of this study was to investigate the short-term effect of levofloxacin on the microbiota of healthy lungs. Material and methods: Male F344 rats received either no levofloxacin (n = 9), intravenous levofloxacin (n = 12), oral levofloxacin (n =  ... Full text Link to item Cite

bcSeq: an R package for fast sequence mapping in high-throughput shRNA and CRISPR screens.

Journal Article Bioinformatics · October 15, 2018 SUMMARY: CRISPR-Cas9 and shRNA high-throughput sequencing screens have abundant applications for basic and translational research. Methods and tools for the analysis of these screens must properly account for sequencing error, resolve ambiguous mappings am ... Full text Link to item Cite

Effect of gastric fluid aspiration on the lung microbiota of laboratory rats.

Journal Article Exp Lung Res · 2018 AIM OF THE STUDY: The pulmonary microbiota is important for both normal homeostasis and the progression of disease, and may be affected by aspiration of gastric fluid. The aim of this study was to investigate changes in the lung microbiota induced by aspir ... Full text Link to item Cite

Fungal genome and mating system transitions facilitated by chromosomal translocations involving intercentromeric recombination.

Journal Article PLoS Biol · August 2017 Species within the human pathogenic Cryptococcus species complex are major threats to public health, causing approximately 1 million annual infections globally. Cryptococcus amylolentus is the most closely known related species of the pathogenic Cryptococc ... Full text Link to item Cite

Elucidation of the calcineurin-Crz1 stress response transcriptional network in the human fungal pathogen Cryptococcus neoformans.

Journal Article PLoS Genet · April 2017 Calcineurin is a highly conserved Ca2+/calmodulin-dependent serine/threonine-specific protein phosphatase that orchestrates cellular Ca2+ signaling responses. In Cryptococcus neoformans, calcineurin is activated by multiple stresses including high temperat ... Full text Link to item Cite

Rapid mapping of insertional mutations to probe cell wall regulation in Cryptococcus neoformans.

Journal Article Fungal Genet Biol · September 2015 Random insertional mutagenesis screens are important tools in microbial genetics studies. Investigators in fungal systems have used the plant pathogen Agrobacterium tumefaciens to create tagged, random mutations for genetic screens in their fungal species ... Full text Link to item Cite

Integrating chemical mutagenesis and whole-genome sequencing as a platform for forward and reverse genetic analysis of Chlamydia.

Journal Article Cell Host Microbe · May 13, 2015 Gene inactivation by transposon insertion or allelic exchange is a powerful approach to probe gene function. Unfortunately, many microbes, including Chlamydia, are not amenable to routine molecular genetic manipulations. Here we describe an arrayed library ... Full text Link to item Cite

Antifungal drug resistance evoked via RNAi-dependent epimutations.

Journal Article Nature · September 25, 2014 Microorganisms evolve via a range of mechanisms that may include or involve sexual/parasexual reproduction, mutators, aneuploidy, Hsp90 and even prions. Mechanisms that may seem detrimental can be repurposed to generate diversity. Here we show that the hum ... Full text Link to item Cite

The genetic architecture of biofilm formation in a clinical isolate of Saccharomyces cerevisiae.

Journal Article Genetics · February 2013 Biofilms are microbial communities that form on surfaces. They are the primary form of microbial growth in nature and can have detrimental impacts on human health. Some strains of the budding yeast Saccharomyces cerevisiae form colony biofilms, and there i ... Full text Link to item Cite

Pleiotropic signaling pathways orchestrate yeast development.

Journal Article Curr Opin Microbiol · December 2011 Developmental phenotypes in Saccharomyces cerevisiae and related yeasts include responses such as filamentous growth, sporulation, and the formation of biofilms and complex colonies. These developmental phenotypes are regulated by evolutionarily conserved, ... Full text Link to item Cite

Outcrossing, mitotic recombination, and life-history trade-offs shape genome evolution in Saccharomyces cerevisiae.

Journal Article Proc Natl Acad Sci U S A · February 1, 2011 We carried out a population genomic survey of Saccharomyces cerevisiae diploid isolates and find that many budding yeast strains have high levels of genomic heterozygosity, much of which is likely due to outcrossing. We demonstrate that variation in hetero ... Full text Link to item Cite

Environmental and genetic determinants of colony morphology in yeast.

Journal Article PLoS Genet · January 22, 2010 Nutrient stresses trigger a variety of developmental switches in the budding yeast Saccharomyces cerevisiae. One of the least understood of such responses is the development of complex colony morphology, characterized by intricate, organized, and strain-sp ... Full text Open Access Link to item Cite

Whole-genome comparison of Leu3 binding in vitro and in vivo reveals the importance of nucleosome occupancy in target site selection.

Journal Article Genome Res · December 2006 Sequence motifs that are potentially recognized by DNA-binding proteins occur far more often in genomic DNA than do observed in vivo protein-DNA interactions. To determine how chromatin influences the utilization of particular DNA-binding sites, we compare ... Full text Link to item Cite

Explicit equilibrium modeling of transcription-factor binding and gene regulation.

Journal Article Genome Biol · 2005 We have developed a computational model that predicts the probability of transcription factor binding to any site in the genome. GOMER (generalizable occupancy model of expression regulation) calculates binding probabilities on the basis of position weight ... Full text Link to item Cite

Identification of cis elements directing termination of yeast nonpolyadenylated snoRNA transcripts.

Journal Article Mol Cell Biol · July 2004 RNA polymerase II (Pol II) termination is triggered by sequences present in the nascent transcript. Termination of pre-mRNA transcription is coupled to recognition of cis-acting sequences that direct cleavage and polyadenylation of the pre-mRNA. Terminatio ... Full text Link to item Cite

Rank order metrics for quantifying the association of sequence features with gene regulation.

Journal Article Bioinformatics · January 22, 2003 MOTIVATION: Genome sequences and transcriptome analyses allow the correlation between gene regulation and DNA sequence features to be studied at the whole-genome level. To quantify these correlations, metrics are needed that can be applied to any sequence ... Full text Link to item Cite

Expression of the vaccinia virus A2.5L redox protein is required for virion morphogenesis.

Journal Article Virology · September 1, 2002 In this article we report the initial biochemical, genetic, and electron microscopic analysis of a previously uncharacterized, 8.9-kDa, predicted thiol-redox protein. The name A2.5L was assigned to the corresponding vaccinia virus gene, which is conserved ... Full text Link to item Cite

The C-terminal domain of the adenine-DNA glycosylase MutY confers specificity for 8-oxoguanine.adenine mispairs and may have evolved from MutT, an 8-oxo-dGTPase.

Journal Article Biochemistry · May 18, 1999 MutY is an adenine-DNA glycosylase with specificity for mismatches involving 8-oxoguanine (oG.A) or guanine (G.A). In addition to a 25 kDa catalytic domain common to all members of its DNA glycosylase superfamily, MutY has a 14 kDa C-terminal domain. Seque ... Full text Link to item Cite