@article{halleran_sylvester_jacob_callahan_baynes_foster_2024, title={Impact of florfenicol dosing regimen on the phenotypic and genotypic resistance of enteric bacteria in steers}, volume={14}, ISSN={["2045-2322"]}, DOI={10.1038/s41598-024-55591-8}, abstractNote={Abstract}, number={1}, journal={SCIENTIFIC REPORTS}, author={Halleran, Jennifer and Sylvester, Hannah and Jacob, Megan and Callahan, Benjamin and Baynes, Ronald and Foster, Derek}, year={2024}, month={Feb} }
 @article{grinevich_harden_thakur_callahan_2024, title={Serovar-level identification of bacterial foodborne pathogens from full-length 16S rRNA gene sequencing}, volume={2}, ISSN={["2379-5077"]}, url={https://doi.org/10.1128/msystems.00757-23}, DOI={10.1128/msystems.00757-23}, abstractNote={ABSTRACT}, journal={MSYSTEMS}, author={Grinevich, Dmitry and Harden, Lyndy and Thakur, Siddhartha and Callahan, Benjamin}, editor={Langille, Morgan G. I.Editor}, year={2024}, month={Feb} }
 @article{scheible_stinson_breen_callahan_thomas_meiklejohn_2024, title={The development of non-destructive sampling methods of parchment skins for genetic species identification}, volume={19}, ISSN={["1932-6203"]}, url={https://doi.org/10.1371/journal.pone.0299524}, DOI={10.1371/journal.pone.0299524}, abstractNote={Parchment, the skins of animals prepared for use as writing surfaces, offers a valuable source of genetic information. Many have clearly defined provenance, allowing for the genetic findings to be evaluated in temporal and spatial context. While these documents can yield evidence of the animal sources, the DNA contained within these aged skins is often damaged and fragmented. Previously, genetic studies targeting parchment have used destructive sampling techniques and so the development and validation of non-destructive sampling methods would expand opportunities and facilitate testing of more precious documents, especially those with historical significance. Here we present genetic data obtained by non-destructive sampling of eight parchments spanning the 15th century to the modern day. We define a workflow for enriching the mitochondrial genome (mtGenome), generating next-generation sequencing reads to permit species identification, and providing interpretation guidance. Using sample replication, comparisons to destructively sampled controls, and by establishing authentication criteria, we were able to confidently assign full/near full mtGenome sequences to 56.3% of non-destructively sampled parchments, each with greater than 90% of the mtGenome reference covered. Six of eight parchments passed all four established thresholds with at least one non-destructive sample, highlighting promise for future studies.}, number={3}, journal={PLOS ONE}, author={Scheible, Melissa and Stinson, Timothy L. and Breen, Matthew and Callahan, Benjamin J. and Thomas, Rachael and Meiklejohn, Kelly A.}, editor={Shakoori, Abdul RaufEditor}, year={2024}, month={Mar} }
 @article{hakimzadeh_abdala asbun_albanese_bernard_buchner_callahan_caporaso_curd_djemiel_brandstrom durling_et al._2023, title={A pile of pipelines: An overview of the bioinformatics software for metabarcoding data analyses}, volume={8}, ISSN={["1755-0998"]}, DOI={10.1111/1755-0998.13847}, abstractNote={Abstract}, journal={MOLECULAR ECOLOGY RESOURCES}, author={Hakimzadeh, Ali and Abdala Asbun, Alejandro and Albanese, Davide and Bernard, Maria and Buchner, Dominik and Callahan, Benjamin and Caporaso, J. Gregory and Curd, Emily and Djemiel, Christophe and Brandstrom Durling, Mikael and et al.}, year={2023}, month={Aug} }
 @article{gin_petzold_uthappa_neighbors_borough_gin_lashnits_sempowski_denny_bienzle_et al._2023, title={Evaluation of SARS-CoV-2 identification methods through surveillance of companion animals in SARS-CoV-2-positive homes in North Carolina, March to December 2020}, volume={11}, ISSN={["2167-8359"]}, DOI={10.7717/peerj.16310}, abstractNote={We collected oral and/or rectal swabs and serum from dogs and cats living in homes with SARS-CoV-2-PCR-positive persons for SARS-CoV-2 PCR and serology testing. Pre-COVID-19 serum samples from dogs and cats were used as negative controls, and samples were tested in duplicate at different timepoints. Raw ELISA results scrutinized relative to known negative samples suggested that cut-offs for IgG seropositivity may require adjustment relative to previously proposed values, while proposed cut-offs for IgM require more extensive validation. A small number of pet dogs (2/43, 4.7%) and one cat (1/21, 4.8%) were positive for SARS-CoV-2 RNA, and 28.6 and 37.5% of cats and dogs were positive for anti-SARS-CoV-2 IgG, respectively.}, journal={PEERJ}, author={Gin, Taylor E. and Petzold, Elizabeth A. and Uthappa, Diya M. and Neighbors, Coralei E. and Borough, Anna R. and Gin, Craig and Lashnits, Erin and Sempowski, Gregory D. and Denny, Thomas and Bienzle, Dorothee and et al.}, year={2023}, month={Oct} }
 @article{gookin_hartley_aicher_mathews_cullen_cullen_callahan_stowe_seiler_jacob_et al._2023, title={Gallbladder microbiota in healthy dogs and dogs with mucocele formation}, volume={18}, ISSN={["1932-6203"]}, DOI={10.1371/journal.pone.0281432}, abstractNote={To date studies have not investigated the culture-independent microbiome of bile from dogs, a species where aseptic collection of bile under ultrasound guidance is somewhat routine. Despite frequent collection of bile for culture-based diagnosis of bacterial cholecystitis, it is unknown whether bile from healthy dogs harbors uncultivable bacteria or a core microbiota. The answer to this question is critical to understanding the pathogenesis of biliary infection and as a baseline to exploration of other biliary diseases in dogs where uncultivable bacteria could play a pathogenic role. A pressing example of such a disease would be gallbladder mucocele formation in dogs. This prevalent and deadly condition is characterized by excessive secretion of abnormal mucus by the gallbladder epithelium that can eventually lead to rupture of the gallbladder or obstruction of bile flow. The cause of mucocele formation is unknown as is whether uncultivable, and therefore unrecognized, bacteria play any systematic role in pathogenesis. In this study we applied next-generation 16S rRNA gene sequencing to identify the culture-negative bacterial community of gallbladder bile from healthy dogs and gallbladder mucus from dogs with mucocele formation. Integral to our study was the use of 2 separate DNA isolations on each sample using different extraction methods and sequencing of negative control samples enabling recognition and curation of contaminating sequences. Microbiota findings were validated by simultaneous culture-based identification, cytological examination of bile, and fluorescence in-situ hybridization (FISH) performed on gallbladder mucosa. Using culture-dependent, cytological, FISH, and 16S rRNA sequencing approaches, results of our study do not support existence of a core microbiome in the bile of healthy dogs or gallbladder mucus from dogs with mucocele formation. Our findings further document how contaminating sequences can significantly contribute to the results of sequencing analysis when performed on samples with low bacterial biomass.}, number={2}, journal={PLOS ONE}, author={Gookin, Jody L. and Hartley, Ashley N. and Aicher, Kathleen M. and Mathews, Kyle G. and Cullen, Rachel and Cullen, John M. and Callahan, Benjamin J. and Stowe, Devorah M. and Seiler, Gabriela S. and Jacob, Megan E. and et al.}, year={2023}, month={Feb} }
 @article{berman_goltsman_anderson_relman_callahan_2023, title={GardnerellaDiversity and Ecology in Pregnancy and Preterm Birth}, url={https://doi.org/10.1101/2023.02.03.527032}, DOI={10.1101/2023.02.03.527032}, abstractNote={Abstract}, author={Berman, Hanna L. and Goltsman, Daniela S. Aliaga and Anderson, Megan and Relman, David A. and Callahan, Benjamin J.}, year={2023}, month={Feb} }
 @article{templeton_fefer_case_roach_azcarate-peril_gruen_callahan_olby_2023, title={Longitudinal Analysis of Canine Oral Microbiome Using Whole Genome Sequencing in Aging Companion Dogs}, volume={13}, ISSN={["2076-2615"]}, DOI={10.3390/ani13243846}, abstractNote={Aged companion dogs have a high prevalence of periodontal disease and canine cognitive dysfunction syndrome (CCDS) and the two disorders are correlated. Similarly, periodontal disease and Alzheimer’s Disease are correlated in people. However, little is known about the oral microbiota of aging dogs. The goal of this project was to characterize the longitudinal changes in oral microbiota in aged dogs. Oral swabs were taken from ten senior client-owned dogs on 2–3 occasions spanning 24 months and they underwent whole genome shotgun (WGS) sequencing. Cognitive status was established at each sampling time. A statistically significant increase in alpha diversity for bacterial and fungal species was observed between the first and last study visits. Bacteroidetes and proteobacteria were the most abundant bacterial phyla. Porphyromonas gulae was the most abundant bacterial species (11.6% of total reads). The species Lactobacillus gasseri had a statistically significant increase in relative abundance with age whereas Leptotrichia sp. oral taxon 212 had a statistically significant positive longitudinal association with cognition score. There is an increased fungal and bacterial alpha diversity in aging dogs over time and nearly universal oral dysbiosis. The role of the oral microbiota, particularly Leptotrichia and P. gulae and P. gingivalis, in aging and CCDS warrants further investigation.}, number={24}, journal={ANIMALS}, author={Templeton, Ginger B. and Fefer, Gilad and Case, Beth C. and Roach, Jeff and Azcarate-Peril, M. Andrea and Gruen, Margaret E. and Callahan, Benjamin J. and Olby, Natasha J.}, year={2023}, month={Dec} }
 @article{huang_gin_fettweis_foxman_gelaye_macintyre_subramaniam_fraser_tabatabaei_callahan_2023, title={Meta-analysis reveals the vaginal microbiome is a better predictor of earlier than later preterm birth}, url={https://doi.org/10.1186/s12915-023-01702-2}, DOI={10.1186/s12915-023-01702-2}, abstractNote={Abstract}, journal={BMC Biology}, author={Huang, Caizhi and Gin, Craig and Fettweis, Jennifer and Foxman, Betsy and Gelaye, Bizu and MacIntyre, David A. and Subramaniam, Akila and Fraser, William and Tabatabaei, Negar and Callahan, Benjamin}, year={2023}, month={Sep} }
 @article{slead_callahan_schreeg_seiler_stowe_azcarate-peril_jacob_gookin_2023, title={Microbiome analysis of bile from apparently healthy cats and cats with suspected hepatobiliary disease}, volume={9}, ISSN={["1939-1676"]}, url={https://doi.org/10.1111/jvim.16852}, DOI={10.1111/jvim.16852}, abstractNote={Abstract}, journal={JOURNAL OF VETERINARY INTERNAL MEDICINE}, author={Slead, Tanner S. and Callahan, Benjamin J. and Schreeg, Megan E. and Seiler, Gabriela S. and Stowe, Devorah M. and Azcarate-Peril, Maria Andrea and Jacob, Megan E. and Gookin, Jody L.}, year={2023}, month={Sep} }
 @article{switzer_callahan_costello_bik_fontaine_gulland_relman_2023, title={Rookery through rehabilitation: Microbial community assembly in newborn harbour seals after maternal separation}, volume={6}, ISSN={["1462-2920"]}, DOI={10.1111/1462-2920.16444}, abstractNote={Abstract}, journal={ENVIRONMENTAL MICROBIOLOGY}, author={Switzer, Alexandra D. and Callahan, Benjamin J. and Costello, Elizabeth K. and Bik, Elisabeth M. and Fontaine, Christine and Gulland, Frances M. D. and Relman, David A.}, year={2023}, month={Jun} }
 @article{grinevich_harden_thakur_callahan_2023, title={Serovar-level Identification of Bacterial Foodborne Pathogens From Full-length 16S rRNA Gene Sequencing}, url={https://doi.org/10.1101/2023.06.28.546915}, DOI={10.1101/2023.06.28.546915}, abstractNote={Abstract}, author={Grinevich, Dmitry and Harden, Lyndy and Thakur, Siddhartha and Callahan, Benjamin J}, year={2023}, month={Jun} }
 @article{manvell_berman_callahan_breitschwerdt_swain_ferris_maggi_lashnits_2022, title={Identification of microbial taxa present in Ctenocephalides felis (cat flea) reveals widespread co-infection and associations with vector phylogeny}, volume={15}, ISSN={["1756-3305"]}, DOI={10.1186/s13071-022-05487-1}, abstractNote={Abstract}, number={1}, journal={PARASITES & VECTORS}, author={Manvell, Charlotte and Berman, Hanna and Callahan, Benjamin and Breitschwerdt, Edward and Swain, William and Ferris, Kelli and Maggi, Ricardo and Lashnits, Erin}, year={2022}, month={Oct} }
 @article{mclaren_nearing_willis_lloyd_callahan_2022, title={Implications of taxonomic bias for microbial differential-abundance analysis}, url={https://doi.org/10.1101/2022.08.19.504330}, DOI={10.1101/2022.08.19.504330}, abstractNote={Abstract}, author={McLaren, Michael R. and Nearing, Jacob T. and Willis, Amy D. and Lloyd, Karen G. and Callahan, Benjamin J.}, year={2022}, month={Aug} }
 @article{huang_gin_fettweis_foxman_gelaye_macintyre_subramaniam_fraser_tabatabaei_callahan_2022, title={Meta-Analysis Reveals the Vaginal Microbiome is a Better Predictor of Earlier Than Later Preterm Birth}, url={https://doi.org/10.1101/2022.09.26.22280389}, DOI={10.1101/2022.09.26.22280389}, abstractNote={High-throughput sequencing measurements of the vaginal microbiome have yielded intriguing potential relationships between the vaginal microbiome and preterm birth (PTB; live birth prior to 37 weeks of gestation). However, results across studies have been inconsistent. Here we perform an integrated analysis of previously published datasets from 12 cohorts of pregnant women whose vaginal microbiomes were measured by 16S rRNA gene sequencing. Of 1926 women included in our analysis, 568 went on to deliver prematurely. Substantial variation between these datasets existed in their definition of preterm birth, characteristics of the study populations, and sequencing methodology. Nevertheless, a small group of taxa comprised a vast majority of the measured microbiome in all cohorts. We trained machine learning (ML) models to predict PTB from the composition of the vaginal microbiome, finding low to modest predictive accuracy (0.28-0.79). Predictive accuracy was typically lower when ML models trained in one dataset predicted PTB in another dataset. Earlier preterm birth (<32 weeks, <34 weeks) was more predictable from the vaginal microbiome than late preterm birth (34 - 37 weeks), both within and across datasets. Integrated differential abundance analysis revealed a highly significant negative association betweenL. crispatusand PTB that was consistent across almost all studies. The presence of the majority (18 out of 25) of genera was associated with a higher risk of PTB, withL. iners, Prevotella, andGardnerellashowing particularly consistent and significant associations. Some example discrepancies between studies could be attributed to specific methodological differences, but not most study-to-study variations in the relationship between the vaginal microbiome and preterm birth. We believe future studies of the vaginal microbiome and PTB will benefit from a focus on earlier preterm births, and improved reporting of specific patient metadata shown to influence the vaginal microbiome and/or birth outcomes.}, author={Huang, Caizhi and Gin, Craig and Fettweis, Jennifer and Foxman, Betsy and Gelaye, Bizu and MacIntyre, David A. and Subramaniam, Akila and Fraser, William and Tabatabaei, Negar and Callahan, Benjamin}, year={2022}, month={Sep} }
 @article{huang_callahan_wu_holloway_brochu_lu_peng_tzeng_2022, title={Phylogeny-guided microbiome OTU-specific association test (POST)}, volume={10}, ISSN={["2049-2618"]}, DOI={10.1186/s40168-022-01266-3}, abstractNote={Abstract}, number={1}, journal={MICROBIOME}, author={Huang, Caizhi and Callahan, Benjamin John and Wu, Michael C. and Holloway, Shannon T. and Brochu, Hayden and Lu, Wenbin and Peng, Xinxia and Tzeng, Jung-Ying}, year={2022}, month={Jun} }
 @article{halleran_callahan_jacob_sylvester_prange_papich_foster_2021, title={Effects of danofloxacin dosing regimen on gastrointestinal pharmacokinetics and fecal microbiome in steers}, volume={11}, ISSN={["2045-2322"]}, DOI={10.1038/s41598-021-90647-z}, abstractNote={Abstract}, number={1}, journal={SCIENTIFIC REPORTS}, author={Halleran, J. L. and Callahan, B. J. and Jacob, M. E. and Sylvester, H. J. and Prange, T. and Papich, M. G. and Foster, D. M.}, year={2021}, month={May} }
 @article{callahan_grinevich_thakur_balamotis_ben yehezkel_2021, title={Ultra-accurate microbial amplicon sequencing with synthetic long reads}, volume={9}, ISSN={["2049-2618"]}, url={https://doi.org/10.1186/s40168-021-01072-3}, DOI={10.1186/s40168-021-01072-3}, abstractNote={Abstract}, number={1}, journal={MICROBIOME}, author={Callahan, Benjamin J. and Grinevich, Dmitry and Thakur, Siddhartha and Balamotis, Michael A. and Ben Yehezkel, Tuval}, year={2021}, month={Jun} }
 @article{thanissery_mclaren_rivera_reed_betrapally_burdette_winston_jacob_callahan_theriot_2020, title={Clostridioides difficile carriage in animals and the associated changes in the host fecal microbiota}, volume={66}, ISSN={["1095-8274"]}, DOI={10.1016/j.anaerobe.2020.102279}, abstractNote={The relationship between the gut microbiota and Clostridioides difficile, and its role in the severity of C. difficile infection in humans is an area of active research. Intestinal carriage of toxigenic and non-toxigenic C. difficile strains, with and without clinical signs, is reported in animals, however few studies have looked at the risk factors associated with C. difficile carriage and the role of the host gut microbiota. Here, we isolated and characterized C. difficile strains from different animal species (predominantly canines (dogs), felines (cats), and equines (horses)) that were brought in for tertiary care at North Carolina State University Veterinary Hospital. C. difficile strains were characterized by toxin gene profiling, fluorescent PCR ribotyping, and antimicrobial susceptibility testing. 16S rRNA gene sequencing was done on animal feces to investigate the relationship between the presence of C. difficile and the gut microbiota in different hosts. Here, we show that C. difficile was recovered from 20.9% of samples (42/201), which included 33 canines, 2 felines, and 7 equines. Over 69% (29/42) of the isolates were toxigenic and belonged to 14 different ribotypes including ones known to cause CDI in humans. The presence of C. difficile results in a shift in the fecal microbial community structure in both canines and equines. Commensal Clostridium hiranonis was negatively associated with C. difficile in canines. Further experimentation showed a clear antagonistic relationship between the two strains in vitro, suggesting that commensal Clostridia might play a role in colonization resistance against C. difficile in different hosts.}, journal={ANAEROBE}, author={Thanissery, R. and McLaren, M. R. and Rivera, A. and Reed, A. D. and Betrapally, N. S. and Burdette, T. and Winston, J. A. and Jacob, M. and Callahan, B. J. and Theriot, C. M.}, year={2020}, month={Dec} }
 @article{mclaren_callahan_2020, title={Pathogen resistance may be the principal evolutionary advantage provided by the microbiome}, volume={375}, url={https://doi.org/10.1098/rstb.2019.0592}, DOI={10.1098/rstb.2019.0592}, abstractNote={To survive, plants and animals must continually defend against pathogenic microbes that would invade and disrupt their tissues. Yet they do not attempt to extirpate all microbes. Instead, they tolerate and even encourage the growth of commensal microbes, which compete with pathogens for resources and via direct inhibition. We argue that hosts have evolved to cooperate with commensals in order to enhance the pathogen resistance this competition provides. We briefly describe competition between commensals and pathogens within the host, consider how natural selection might favour hosts that tilt this competition in favour of commensals, and describe examples of extant host traits that may serve this purpose. Finally, we consider ways that this cooperative immunity may have facilitated the adaptive evolution of non-pathogen-related host traits. On the basis of these observations, we argue that pathogen resistance vies with other commensal-provided benefits for being the principal evolutionary advantage provided by the microbiome to host lineages across the tree of life.}, number={1808}, journal={Philosophical Transactions of the Royal Society B: Biological Sciences}, publisher={The Royal Society}, author={McLaren, Michael R. and Callahan, Benjamin J.}, year={2020}, month={Sep}, pages={20190592} }
 @article{kolodny_callahan_douglas_2020, title={The role of the microbiome in host evolution}, volume={375}, url={https://doi.org/10.1098/rstb.2019.0588}, DOI={10.1098/rstb.2019.0588}, abstractNote={In the last decade, we have witnessed a major paradigm shift in the life sciences: the recognition that the microbiome, i.e. the set of microorganisms associated with healthy animals (including humans) and plants, plays a crucial role in the sustained health and fitness of its host. Enabled by rapid advances in sequencing technologies and analytical methods, substantial advances have been achieved in both identifying the microbial taxa and understanding the relationship between microbiome composition and host phenotype. These breakthroughs are leading to novel strategies for improved human and animal health, enhanced crop yield and nutritional quality, and the control of various pests and disease agents.}, number={1808}, journal={Philosophical Transactions of the Royal Society B: Biological Sciences}, publisher={The Royal Society}, author={Kolodny, Oren and Callahan, Benjamin J. and Douglas, Angela E.}, year={2020}, month={Sep}, pages={20190588} }
 @article{callahan_grinevich_thakur_balamotis_yehezkel_2020, title={Ultra-accurate Microbial Amplicon Sequencing Directly from Complex Samples with Synthetic Long Reads}, volume={7}, url={https://doi.org/10.1101/2020.07.07.192286}, DOI={10.1101/2020.07.07.192286}, abstractNote={Abstract}, publisher={Cold Spring Harbor Laboratory}, author={Callahan, Benjamin J and Grinevich, Dmitry and Thakur, Siddhartha and Balamotis, Michael A and Yehezkel, Tuval Ben}, year={2020}, month={Jul} }
 @article{berman_mclaren_callahan_2020, title={Understanding and interpreting community sequencing measurements of the vaginal microbiome}, volume={127}, url={https://doi.org/10.1111/1471-0528.15978}, DOI={10.1111/1471-0528.15978}, abstractNote={Community‐wide high‐throughput sequencing has transformed the study of the vaginal microbiome, and clinical applications are on the horizon. Here we outline the three main community sequencing methods: (1) amplicon sequencing, (2) shotgun metagenomic sequencing, and (3) metatranscriptomic sequencing. We discuss the advantages and limitations of community sequencing generally, and the unique strengths and weaknesses of each method. We briefly review the contributions of community sequencing to vaginal microbiome research and practice. We develop suggestions for critically interpreting research results and potential clinical applications based on community sequencing of the vaginal microbiome.}, number={2}, journal={BJOG: An International Journal of Obstetrics & Gynaecology}, publisher={Wiley}, author={Berman, HL and McLaren and Callahan, BJ}, year={2020}, month={Jan}, pages={139–146} }
 @article{foster_jacob_farmer_callahan_theriot_kathariou_cernicchiaro_prange_papich_2019, title={Ceftiofur formulation differentially affects the intestinal drug concentration, resistance of fecal Escherichia coli, and the microbiome of steers}, volume={14}, ISSN={["1932-6203"]}, DOI={10.1371/journal.pone.0223378}, abstractNote={Antimicrobial drug concentrations in the gastrointestinal tract likely drive antimicrobial resistance in enteric bacteria. Our objective was to determine the concentration of ceftiofur and its metabolites in the gastrointestinal tract of steers treated with ceftiofur crystalline-free acid (CCFA) or ceftiofur hydrochloride (CHCL), determine the effect of these drugs on the minimum inhibitory concentration (MIC) of fecal Escherichia coli, and evaluate shifts in the microbiome. Steers were administered either a single dose (6.6 mg/kg) of CCFA or 2.2 mg/kg of CHCL every 24 hours for 3 days. Ceftiofur and its metabolites were measured in the plasma, interstitium, ileum and colon. The concentration and MIC of fecal E. coli and the fecal microbiota composition were assessed after treatment. The maximum concentration of ceftiofur was higher in all sampled locations of steers treated with CHCL. Measurable drug persisted longer in the intestine of CCFA-treated steers. There was a significant decrease in E. coli concentration (P = 0.002) within 24 hours that persisted for 2 weeks after CCFA treatment. In CHCL-treated steers, the mean MIC of ceftiofur in E. coli peaked at 48 hours (mean MIC = 20.45 ug/ml, 95% CI = 10.29–40.63 ug/ml), and in CCFA-treated steers, mean MIC peaked at 96 hours (mean MIC = 10.68 ug/ml, 95% CI = 5.47–20.85 ug/ml). Shifts in the microbiome of steers in both groups were due to reductions in Firmicutes and increases in Bacteroidetes. CCFA leads to prolonged, low intestinal drug concentrations, and is associated with decreased E. coli concentration, an increased MIC of ceftiofur in E. coli at specific time points, and shifts in the fecal microbiota. CHCL led to higher intestinal drug concentrations over a shorter duration. Effects on E. coli concentration and the microbiome were smaller in this group, but the increase in the MIC of ceftiofur in fecal E. coli was similar.}, number={10}, journal={PLOS ONE}, author={Foster, Derek M. and Jacob, Megan E. and Farmer, Kyle A. and Callahan, Benjamin J. and Theriot, Casey M. and Kathariou, Sophia and Cernicchiaro, Natalia and Prange, Timo and Papich, Mark G.}, year={2019}, month={Oct} }
 @article{mclaren_willis_callahan_2019, title={Consistent and correctable bias in metagenomic sequencing experiments}, volume={2}, url={https://doi.org/10.1101/559831}, DOI={10.1101/559831}, abstractNote={Abstract}, journal={bioRxiv}, publisher={Cold Spring Harbor Laboratory}, author={McLaren, Michael R. and Willis, Amy D. and Callahan, Benjamin J.}, year={2019}, month={Feb}, pages={559831} }
 @article{mclaren_willis_callahan_2019, title={Consistent and correctable bias in metagenomic sequencing experiments}, url={https://doi.org/10.7554/eLife.46923}, DOI={10.7554/eLife.46923}, abstractNote={Marker-gene and metagenomic sequencing have profoundly expanded our ability to measure biological communities. But the measurements they provide differ from the truth, often dramatically, because these experiments are biased toward detecting some taxa over others. This experimental bias makes the taxon or gene abundances measured by different protocols quantitatively incomparable and can lead to spurious biological conclusions. We propose a mathematical model for how bias distorts community measurements based on the properties of real experiments. We validate this model with 16S rRNA gene and shotgun metagenomics data from defined bacterial communities. Our model better fits the experimental data despite being simpler than previous models. We illustrate how our model can be used to evaluate protocols, to understand the effect of bias on downstream statistical analyses, and to measure and correct bias given suitable calibration controls. These results illuminate new avenues toward truly quantitative and reproducible metagenomics measurements.}, journal={eLife}, author={McLaren, Michael R and Willis, Amy D and Callahan, Benjamin J}, year={2019}, month={Sep} }
 @article{callahan_wong_heiner_oh_theriot_gulati_mcgill_dougherty_2019, title={High-throughput amplicon sequencing of the full-length 16S rRNA gene with single-nucleotide resolution}, volume={7}, url={https://doi.org/10.1093/nar/gkz569}, DOI={10.1093/nar/gkz569}, abstractNote={Abstract}, journal={Nucleic Acids Research}, publisher={Oxford University Press (OUP)}, author={Callahan, Benjamin J and Wong, Joan and Heiner, Cheryl and Oh, Steve and Theriot, Casey M and Gulati, Ajay S and McGill, Sarah K and Dougherty, Michael K}, year={2019}, month={Oct} }
 @article{ghaemi_digiulio_contrepois_callahan_ngo_lee-mcmullen_lehallier_robaczewska_mcilwain_rosenberg-hasson_et al._2019, title={Multiomics modeling of the immunome, transcriptome, microbiome, proteome and metabolome adaptations during human pregnancy}, volume={35}, ISSN={["1460-2059"]}, url={https://doi.org/10.1093/bioinformatics/bty537}, DOI={10.1093/bioinformatics/bty537}, abstractNote={Abstract}, number={1}, journal={BIOINFORMATICS}, publisher={Oxford University Press (OUP)}, author={Ghaemi, Mohammad Sajjad and DiGiulio, Daniel B. and Contrepois, Kevin and Callahan, Benjamin and Ngo, Thuy T. M. and Lee-McMullen, Brittany and Lehallier, Benoit and Robaczewska, Anna and Mcilwain, David and Rosenberg-Hasson, Yael and et al.}, editor={Wren, JonathanEditor}, year={2019}, month={Jan}, pages={95–103} }
 @article{callahan_wong_heiner_oh_theriot_gulati_mcgill_dougherty_2018, title={High-throughput amplicon sequencing of the full-length 16S rRNA gene with single-nucleotide resolution}, volume={8}, url={https://doi.org/10.1101/392332}, DOI={10.1101/392332}, abstractNote={Abstract}, publisher={Cold Spring Harbor Laboratory}, author={Callahan, Benjamin J and Wong, Joan and Heiner, Cheryl and Oh, Steve and Theriot, Casey M and Gulati, Ajay S and McGill, Sarah K and Dougherty, Michael K}, year={2018}, month={Aug} }
 @article{mclaren_callahan_2018, title={In Nature, There Is Only Diversity}, volume={9}, ISSN={["2150-7511"]}, url={http://www.ncbi.nlm.nih.gov/pubmed/29295915}, DOI={10.1128/mbio.02149-17}, abstractNote={ABSTRACT}, number={1}, journal={MBIO}, publisher={American Society for Microbiology}, author={McLaren, Michael R. and Callahan, Benjamin J.}, year={2018} }
 @article{davis_proctor_holmes_relman_callahan_2018, title={Simple statistical identification and removal of contaminant sequences in marker-gene and metagenomics data}, volume={6}, ISSN={["2049-2618"]}, url={https://doi.org/10.1186/s40168-018-0605-2}, DOI={10.1186/s40168-018-0605-2}, abstractNote={The accuracy of microbial community surveys based on marker-gene and metagenomic sequencing (MGS) suffers from the presence of contaminants-DNA sequences not truly present in the sample. Contaminants come from various sources, including reagents. Appropriate laboratory practices can reduce contamination, but do not eliminate it. Here we introduce decontam ( https://github.com/benjjneb/decontam ), an open-source R package that implements a statistical classification procedure that identifies contaminants in MGS data based on two widely reproduced patterns: contaminants appear at higher frequencies in low-concentration samples and are often found in negative controls.Decontam classified amplicon sequence variants (ASVs) in a human oral dataset consistently with prior microscopic observations of the microbial taxa inhabiting that environment and previous reports of contaminant taxa. In metagenomics and marker-gene measurements of a dilution series, decontam substantially reduced technical variation arising from different sequencing protocols. The application of decontam to two recently published datasets corroborated and extended their conclusions that little evidence existed for an indigenous placenta microbiome and that some low-frequency taxa seemingly associated with preterm birth were contaminants.Decontam improves the quality of metagenomic and marker-gene sequencing by identifying and removing contaminant DNA sequences. Decontam integrates easily with existing MGS workflows and allows researchers to generate more accurate profiles of microbial communities at little to no additional cost.}, number={1}, journal={MICROBIOME}, publisher={Springer Science and Business Media LLC}, author={Davis, Nicole M. and Proctor, Diana M. and Holmes, Susan P. and Relman, David A. and Callahan, Benjamin J.}, year={2018}, month={Dec} }
 @article{callahan_mcmurdie_holmes_2017, title={Exact sequence variants should replace operational taxonomic units in marker-gene data analysis}, volume={11}, ISSN={1751-7362 1751-7370}, url={http://dx.doi.org/10.1038/ismej.2017.119}, DOI={10.1038/ismej.2017.119}, abstractNote={Abstract}, number={12}, journal={The ISME Journal}, publisher={Springer Science and Business Media LLC}, author={Callahan, Benjamin J and McMurdie, Paul J and Holmes, Susan P}, year={2017}, month={Jul}, pages={2639–2643} }
 @article{callahan_digiulio_goltsman_sun_costello_jeganathan_biggio_wong_druzin_shaw_et al._2017, title={Replication and refinement of a vaginal microbial signature of preterm birth in two racially distinct cohorts of US women}, volume={114}, ISSN={["0027-8424"]}, DOI={10.1073/pnas.1705899114}, abstractNote={Significance}, number={37}, journal={PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA}, author={Callahan, Benjamin J. and DiGiulio, Daniel B. and Goltsman, Daniela S. Aliaga and Sun, Christine L. and Costello, Elizabeth K. and Jeganathan, Pratheepa and Biggio, Joseph R. and Wong, Ronald J. and Druzin, Maurice L. and Shaw, Gary M. and et al.}, year={2017}, month={Sep}, pages={9966–9971} }
 @article{callahan_digiulio_goltsman_sun_costello_jeganathan_biggio_wong_druzin_shaw_et al._2017, title={Replication and refinement of a vaginal microbial signature of preterm birth in two racially distinct cohorts of US women}, journal={Proceedings of the National Academy of Sciences}, publisher={National Acad Sciences}, author={Callahan, Benjamin J and DiGiulio, Daniel B and Goltsman, Daniela S Aliaga and Sun, Christine L and Costello, Elizabeth K and Jeganathan, Pratheepa and Biggio, Joseph R and Wong, Ronald J and Druzin, Maurice L and Shaw, Gary M and et al.}, year={2017}, pages={201705899} }
 @article{davis_proctor_holmes_relman_callahan_2017, title={Simple statistical identification and removal of contaminant sequences in marker-gene and metagenomics data}, volume={11}, url={https://doi.org/10.1101/221499}, DOI={10.1101/221499}, abstractNote={Abstract}, publisher={Cold Spring Harbor Laboratory}, author={Davis, Nicole M. and Proctor, Diana M. and Holmes, Susan P. and Relman, David A. and Callahan, Benjamin J.}, year={2017}, month={Nov} }
 @article{mayer-blackwell_fincker_molenda_callahan_sewell_holmes_edwards_spormann_2016, title={1,2-Dichloroethane Exposure Alters the Population Structure, Metabolism, and Kinetics of a Trichloroethene-Dechlorinating Dehalococcoides mccartyi Consortium}, volume={50}, ISSN={0013-936X 1520-5851}, url={http://dx.doi.org/10.1021/acs.est.6b02957}, DOI={10.1021/acs.est.6b02957}, abstractNote={Bioremediation of groundwater contaminated with chlorinated aliphatic hydrocarbons such as perchloroethene and trichloroethene can result in the accumulation of the undesirable intermediate vinyl chloride. Such accumulation can either be due to the absence of specific vinyl chloride respiring Dehalococcoides mccartyi or to the inhibition of such strains by the metabolism of other microorganisms. The fitness of vinyl chloride respiring Dehalococcoides mccartyi subpopulations is particularly uncertain in the presence of chloroethene/chloroethane cocontaminant mixtures, which are commonly found in contaminated groundwater. Therefore, we investigated the structure of Dehalococcoides populations in a continuously fed reactor system under changing chloroethene/ethane influent conditions. We observed that increasing the influent ratio of 1,2-dichloroethane to trichloroethene was associated with ecological selection of a tceA-containing Dehalococcoides population relative to a vcrA-containing Dehalococcoides population. Although both vinyl chloride and 1,2-dichloroethane could be simultaneously transformed to ethene, prolonged exposure to 1,2-dichloroethane diminished the vinyl chloride transforming capacity of the culture. Kinetic tests revealed that dechlorination of 1,2-dichloroethane by the consortium was strongly inhibited by cis-dichloroethene but not vinyl chloride. Native polyacrylamide gel electrophoresis and mass spectrometry revealed that a trichloroethene reductive dehalogenase (TceA) homologue was the most consistently expressed of four detectable reductive dehalogenases during 1,2-dichloroethane exposure, suggesting that it catalyzes the reductive dihaloelimination of 1,2-dichloroethane to ethene.}, number={22}, journal={Environmental Science & Technology}, publisher={American Chemical Society (ACS)}, author={Mayer-Blackwell, Koshlan and Fincker, Maeva and Molenda, Olivia and Callahan, Benjamin and Sewell, Holly and Holmes, Susan and Edwards, Elizabeth A. and Spormann, Alfred M.}, year={2016}, month={Nov}, pages={12187–12196} }
 @article{callahan_sankaran_fukuyama_mcmurdie_holmes_2016, title={Bioconductor Workflow for Microbiome Data Analysis: from raw reads to community analyses}, volume={5}, ISSN={2046-1402}, url={http://dx.doi.org/10.12688/f1000research.8986.2}, DOI={10.12688/f1000research.8986.2}, abstractNote={High-throughput sequencing of PCR-amplified taxonomic markers (like the 16S rRNA gene) has enabled a new level of analysis of complex bacterial communities known as microbiomes. Many tools exist to quantify and compare abundance levels or OTU composition of communities in different conditions. The sequencing reads have to be denoised and assigned to the closest taxa from a reference database. Common approaches use a notion of 97% similarity and normalize the data by subsampling to equalize library sizes. In this paper, we show that statistical models allow more accurate abundance estimates. By providing a complete workflow in R, we enable the user to do sophisticated downstream statistical analyses, whether parametric or nonparametric. We provide examples of using the R packages dada2, phyloseq, DESeq2, ggplot2 and vegan to filter, visualize and test microbiome data. We also provide examples of supervised analyses using random forests and nonparametric testing using community networks and the ggnetwork package.}, journal={F1000Research}, publisher={F1000 ( Faculty of 1000 Ltd)}, author={Callahan, Ben J. and Sankaran, Kris and Fukuyama, Julia A. and McMurdie, Paul J. and Holmes, Susan P.}, year={2016}, month={Nov}, pages={1492} }
 @article{callahan_mcmurdie_rosen_han_johnson_holmes_2016, title={DADA2: High-resolution sample inference from Illumina amplicon data}, volume={13}, ISSN={1548-7091 1548-7105}, url={http://dx.doi.org/10.1038/nmeth.3869}, DOI={10.1038/nmeth.3869}, abstractNote={DADA2 is an open-source software package that denoises and removes sequencing errors from Illumina amplicon sequence data to distinguish microbial sample sequences differing by as little as a single nucleotide. We present the open-source software package DADA2 for modeling and correcting Illumina-sequenced amplicon errors ( https://github.com/benjjneb/dada2 ). DADA2 infers sample sequences exactly and resolves differences of as little as 1 nucleotide. In several mock communities, DADA2 identified more real variants and output fewer spurious sequences than other methods. We applied DADA2 to vaginal samples from a cohort of pregnant women, revealing a diversity of previously undetected Lactobacillus crispatus variants.}, number={7}, journal={Nature Methods}, publisher={Springer Nature}, author={Callahan, Benjamin J and McMurdie, Paul J and Rosen, Michael J and Han, Andrew W and Johnson, Amy Jo A and Holmes, Susan P}, year={2016}, month={May}, pages={581–583} }
 @article{bik_costello_switzer_callahan_holmes_wells_carlin_jensen_venn-watson_relman_2016, title={Marine mammals harbor unique microbiotas shaped by and yet distinct from the sea}, volume={7}, ISSN={2041-1723}, url={http://dx.doi.org/10.1038/ncomms10516}, DOI={10.1038/ncomms10516}, abstractNote={Abstract}, number={1}, journal={Nature Communications}, publisher={Springer Science and Business Media LLC}, author={Bik, Elisabeth M. and Costello, Elizabeth K. and Switzer, Alexandra D. and Callahan, Benjamin J. and Holmes, Susan P. and Wells, Randall S. and Carlin, Kevin P. and Jensen, Eric D. and Venn-Watson, Stephanie and Relman, David A.}, year={2016}, month={Feb}, pages={10516} }
 @article{callahan_proctor_relman_fukuyama_holmes_2016, title={Reproducible research workflow in R for the analysis of personalized human microbiome data}, volume={21}, journal={Pacific Symposium on Biocomputing}, author={Callahan, B.J. and Proctor, D. and Relman, D.A. and Fukuyama, J. and Holmes, S.P.}, year={2016}, pages={183–194} }
 @inproceedings{callahan_proctor_relman_fukuyama_holmes_2016, title={Reproducible research workflow in R for the analysis of personalized human microbiome data}, volume={21}, booktitle={Pacific Symposium on Biocomputing. Pacific Symposium on Biocomputing}, author={Callahan, Benjamin and Proctor, Diana and Relman, David and Fukuyama, Julia and Holmes, Susan}, year={2016}, pages={183} }
 @article{digiulio_callahan_mcmurdie_costello_lyell_robaczewska_sun_goltsman_wong_shaw_et al._2015, title={Temporal and spatial variation of the human microbiota during pregnancy}, volume={112}, ISSN={0027-8424 1091-6490}, url={http://dx.doi.org/10.1073/pnas.1502875112}, DOI={10.1073/pnas.1502875112}, abstractNote={Significance}, number={35}, journal={Proceedings of the National Academy of Sciences}, publisher={Proceedings of the National Academy of Sciences}, author={DiGiulio, Daniel B. and Callahan, Benjamin J. and McMurdie, Paul J. and Costello, Elizabeth K. and Lyell, Deirdre J. and Robaczewska, Anna and Sun, Christine L. and Goltsman, Daniela S. A. and Wong, Ronald J. and Shaw, Gary and et al.}, year={2015}, month={Aug}, pages={11060–11065} }
 @article{digiulio_callahan_mcmurdie_costello_lyell_robaczewska_sun_goltsman_wong_shaw_et al._2015, title={Temporal and spatial variation of the human microbiota during pregnancy}, volume={112}, number={35}, journal={Proceedings of the National Academy of Sciences}, publisher={National Acad Sciences}, author={DiGiulio, Daniel B and Callahan, Benjamin J and McMurdie, Paul J and Costello, Elizabeth K and Lyell, Deirdre J and Robaczewska, Anna and Sun, Christine L and Goltsman, Daniela SA and Wong, Ronald J and Shaw, Gary and et al.}, year={2015}, pages={11060–11065} }
 @article{callahan_fukami_fisher_2014, title={Rapid evolution of adaptive niche construction in experimental microbial populations}, volume={68}, ISSN={0014-3820}, url={http://dx.doi.org/10.1111/evo.12512}, DOI={10.1111/evo.12512}, abstractNote={Many species engage in adaptive niche construction: modification of the local environment that increases the modifying organism's competitive fitness. Adaptive niche construction provides an alternative pathway to higher fitness, shaping the environment rather than conforming to it. Yet, experimental evidence for the evolutionary emergence of adaptive niche construction is lacking, leaving its role in evolution uncertain. Here we report a direct observation of the de novo evolution of adaptive niche construction in populations of the bacteria Pseudomonas fluorescens. In a laboratory experiment, we allowed several bacterial populations to adapt to a novel environment and assessed whether niche construction evolved over time. We found that adaptive niche construction emerged rapidly, within approximately 100 generations, and became ubiquitous after approximately 400 generations. The large fitness effect of this niche construction was dominated by the low fitness of evolved strains in the ancestrally modified environment: evolved niche constructors were highly dependent on their specific environmental modifications. Populations were subjected to frequent resetting of environmental conditions and severe reduction of spatial habitat structure, both of which are thought to make adaptive niche construction difficult to evolve. Our finding that adaptive niche construction nevertheless evolved repeatably suggests that it may play a more important role in evolution than generally thought.}, number={11}, journal={Evolution}, publisher={Wiley}, author={Callahan, Benjamin J. and Fukami, Tadashi and Fisher, Daniel S.}, year={2014}, month={Sep}, pages={3307–3316} }
 @article{walker_callahan_arya_barry_bhattacharya_grigoryev_pellegrini_rippe_rosenberg_2013, title={Evolutionary dynamics and information hierarchies in biological systems}, volume={1305}, ISSN={0077-8923}, url={http://dx.doi.org/10.1111/nyas.12140}, DOI={10.1111/nyas.12140}, abstractNote={The study of evolution has entered a revolutionary new era, where quantitative and predictive methods are transforming the traditionally qualitative and retrospective approaches of the past. Genomic sequencing and modern computational techniques are permitting quantitative comparisons between variation in the natural world and predictions rooted in neo‐Darwinian theory, revealing the shortcomings of current evolutionary theory, particularly with regard to large‐scale phenomena like macroevolution. Current research spanning and uniting diverse fields and exploring the physical and chemical nature of organisms across temporal, spatial, and organizational scales is replacing the model of evolution as a passive filter selecting for random changes at the nucleotide level with a paradigm in which evolution is a dynamic process both constrained and driven by the informational architecture of organisms across scales, from DNA and chromatin regulation to interactions within and between species and the environment.}, number={1}, journal={Annals of the New York Academy of Sciences}, publisher={Wiley}, author={Walker, Sara Imari and Callahan, Benjamin J. and Arya, Gaurav and Barry, J. David and Bhattacharya, Tanmoy and Grigoryev, Sergei and Pellegrini, Matteo and Rippe, Karsten and Rosenberg, Susan M.}, year={2013}, month={May}, pages={1–17} }
 @article{rosen_callahan_fisher_holmes_2012, title={Denoising PCR-amplified metagenome data}, volume={13}, number={1}, journal={BMC bioinformatics}, publisher={BioMed Central}, author={Rosen, M.J. and Callahan, B.J. and Fisher, D.S. and Holmes, S.P.}, year={2012}, pages={283} }
 @article{callahan_2012, title={The length scale of selection in protein evolution}, volume={6}, ISSN={1933-6934 1933-6942}, url={http://dx.doi.org/10.4161/fly.18305}, DOI={10.4161/fly.18305}, abstractNote={Central to the study of molecular evolution, and an area of long-standing debate, is the appropriate model for the fitness landscape of proteins. Much of this debate has focused on the strength and frequency of positive and purifying selection, but the form and frequency of selective correlations is also a vital element. The constituent amino acids within a protein generically interact and share selective pressures in predictable ways, which conflicts with the selective independence assumed by common caricatures of the fitness landscape. Here, I discuss a recent study by myself and coauthors1 that used whole-genome comparisons of orthologous molecular sequences from closely related Drosophilids to explore the form of the selective correlations and selective interactions (epistasis) between the amino acids within a protein. I outline our results and highlight our finding of a selective length scale of ten amino acids within which individual amino acids are substantially and generically more likely to share selective pressures and interact epistatically. I then focus on the evidence presented in our study supporting a substantial role for epistasis in the process of molecular evolution, and discuss further the implications of this widespread epistasis on the overdispersion of the molecular clock and the efficacy of common tests for positive selection.}, number={1}, journal={Fly}, publisher={Informa UK Limited}, author={Callahan, Benjamin J.}, year={2012}, month={Jan}, pages={16–20} }
 @article{callahan_neher_bachtrog_andolfatto_shraiman_2011, title={Correlated Evolution of Nearby Residues in Drosophilid Proteins}, volume={7}, ISSN={1553-7404}, url={http://dx.doi.org/10.1371/journal.pgen.1001315}, DOI={10.1371/journal.pgen.1001315}, abstractNote={Here we investigate the correlations between coding sequence substitutions as a function of their separation along the protein sequence. We consider both substitutions between the reference genomes of several Drosophilids as well as polymorphisms in a population sample of Zimbabwean Drosophila melanogaster. We find that amino acid substitutions are “clustered” along the protein sequence, that is, the frequency of additional substitutions is strongly enhanced within ≈10 residues of a first such substitution. No such clustering is observed for synonymous substitutions, supporting a “correlation length” associated with selection on proteins as the causative mechanism. Clustering is stronger between substitutions that arose in the same lineage than it is between substitutions that arose in different lineages. We consider several possible origins of clustering, concluding that epistasis (interactions between amino acids within a protein that affect function) and positional heterogeneity in the strength of purifying selection are primarily responsible. The role of epistasis is directly supported by the tendency of nearby substitutions that arose on the same lineage to preserve the total charge of the residues within the correlation length and by the preferential cosegregation of neighboring derived alleles in our population sample. We interpret the observed length scale of clustering as a statistical reflection of the functional locality (or modularity) of proteins: amino acids that are near each other on the protein backbone are more likely to contribute to, and collaborate toward, a common subfunction.}, number={2}, journal={PLoS Genetics}, publisher={Public Library of Science (PLoS)}, author={Callahan, Benjamin and Neher, Richard A. and Bachtrog, Doris and Andolfatto, Peter and Shraiman, Boris I.}, editor={McVean, GilEditor}, year={2011}, month={Feb}, pages={e1001315} }
 @article{sellis_callahan_petrov_messer_2011, title={Heterozygote advantage as a natural consequence of adaptation in diploids}, volume={108}, ISSN={0027-8424 1091-6490}, url={http://dx.doi.org/10.1073/pnas.1114573108}, DOI={10.1073/pnas.1114573108}, abstractNote={Molecular adaptation is typically assumed to proceed by sequential fixation of beneficial mutations. In diploids, this picture presupposes that for most adaptive mutations, the homozygotes have a higher fitness than the heterozygotes. Here, we show that contrary to this expectation, a substantial proportion of adaptive mutations should display heterozygote advantage. This feature of adaptation in diploids emerges naturally from the primary importance of the fitness of heterozygotes for the invasion of new adaptive mutations. We formalize this result in the framework of Fisher's influential geometric model of adaptation. We find that in diploids, adaptation should often proceed through a succession of short-lived balanced states that maintain substantially higher levels of phenotypic and fitness variation in the population compared with classic adaptive walks. In fast-changing environments, this variation produces a diversity advantage that allows diploids to remain better adapted compared with haploids despite the disadvantage associated with the presence of unfit homozygotes. The short-lived balanced states arising during adaptive walks should be mostly invisible to current scans for long-term balancing selection. Instead, they should leave signatures of incomplete selective sweeps, which do appear to be common in many species. Our results also raise the possibility that balancing selection, as a natural consequence of frequent adaptation, might play a more prominent role among the forces maintaining genetic variation than is commonly recognized.}, number={51}, journal={Proceedings of the National Academy of Sciences}, publisher={Proceedings of the National Academy of Sciences}, author={Sellis, D. and Callahan, B. J. and Petrov, D. A. and Messer, P. W.}, year={2011}, month={Dec}, pages={20666–20671} }
 @article{callahan_thattai_shraiman_2009, title={Emergent gene order in a model of modular polyketide synthases}, volume={106}, ISSN={0027-8424 1091-6490}, url={http://dx.doi.org/10.1073/pnas.0902364106}, DOI={10.1073/pnas.0902364106}, abstractNote={Polyketides are a class of biologically active heteropolymers produced by assembly line-like multiprotein complexes of modular polyketide synthases (PKS). The polyketide product is encoded in the order of the PKS proteins in the assembly line, suggesting that polyketide diversity derives from combinatorial rearrangement of these PKS complexes. Remarkably, the order of PKS genes on the chromosome follows the order of PKS proteins in the assembly line: This fact is commonly referred to as “collinearity”. Here we propose an evolutionary origin for collinearity and demonstrate the mechanism by using a computational model of PKS evolution in a population. Assuming continuous evolutionary pressure for novel polyketides, and that new polyketide pathways are formed by horizontal transfer/recombination of PKS-encoding DNA, we demonstrate the existence of a broad range of parameters for which collinearity emerges spontaneously. Collinearity confers no fitness advantage in our model; it is established and maintained through a “secondary selection” mechanism, as a trait which increases the probability of forming long, novel PKS complexes through recombination. Consequently, collinearity hitchhikes on the successful genotypes which periodically sweep through the evolving population. In addition to computer simulation of a simplified model of PKS evolution, we provide a mathematical framework describing the secondary selection mechanism, which generalizes beyond the context of the present model.}, number={46}, journal={Proceedings of the National Academy of Sciences}, publisher={Proceedings of the National Academy of Sciences}, author={Callahan, B. and Thattai, M. and Shraiman, B. I.}, year={2009}, month={Oct}, pages={19410–19415} }
 @phdthesis{callahan_2009, title={Evolution on an interacting fitness landscape: The effects of the interplay of epistasis and recombination on genetic structure}, school={University of California, Santa Barbara}, author={Callahan, Benjamin J}, year={2009} }
 @article{cheung_finke_callahan_onuchic_2003, title={Exploring the Interplay between Topology and Secondary Structural Formation in the Protein Folding Problem}, volume={107}, ISSN={1520-6106 1520-5207}, url={http://dx.doi.org/10.1021/jp034441r}, DOI={10.1021/jp034441r}, abstractNote={models) have been successful in providing a qualitativeunderstanding of the folding mechanism of small globular proteins. Can we go beyond this qualitativeunderstanding and make more detailed quantitative connections to experiments? To achieve this goal, a tractableframework of protein representations whose complexity falls between C}, number={40}, journal={The Journal of Physical Chemistry B}, publisher={American Chemical Society (ACS)}, author={Cheung, Margaret S. and Finke, John M. and Callahan, Benjamin and Onuchic, José N.}, year={2003}, month={Oct}, pages={11193–11200} }