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1. Molecular Transducers of Physical Activity Consortium (MoTrPAC): human studies design and protocol

Author

Group, MoTrPAC Study, Jakicic, John M, Kohrt, Wendy M, Houmard, Joseph A, Miller, Michael E, Radom-Aizik, Shlomit, Rasmussen, Blake B, Ravussin, Eric, Serra, Monica, Stowe, Cynthia L, Trappe, Scott, Abouassi, Hiba, Adkins, Joshua N, Alekel, D Lee, Ashley, Euan, Bamman, Marcas M, Bergman, Bryan C, Bessesen, Daniel H, Broskey, Nicholas T, Buford, Thomas W, Burant, Charles F, Chen, Haiying, Christle, Jeffrey W, Clish, Clary B, Coen, Paul M, Collier, David, Collins, Katherine A, Cooper, Daniel M, Cortes, Tiffany, Cutter, Gary R, Dubis, Gabriel, Fernández, Facundo M, Firnhaber, Jonathon, Forman, Daniel E, Gaul, David A, Gay, Nicole, Gerszten, Robert E, Goodpaster, Bret H, Gritsenko, Marina A, Haddad, Fadia, Huffman, Kim M, Ilkayeva, Olga, Jankowski, Catherine M, Jin, Christopher, Johannsen, Neil M, Johnson, Johanna, Kelly, Leslie, Kershaw, Erin, Kraus, William E, Laughlin, Maren, Lester, Bridget, Lindholm, Malene E, Lowe, Adam, Lu, Ching-Ju, McGowan, Joan, Melanson, Edward L, Montgomery, Stephen, Moore, Samuel G, Moreau, Kerrie L, Muehlbauer, Michael, Musi, Nicolas, Nair, Venugopalan D, Newgard, Christopher B, Newman, Anne B, Nicklas, Barbara, Nindl, Bradley C, Ormond, Kelly, Piehowski, Paul D, Qian, Wei-Jun, Rankinen, Tuomo, Rejeski, W Jack, Robbins, Jeremy, Rogers, Renee J, Rooney, Jessica L, Rushing, Scott, Sanford, James A, Schauer, Irene E, Schwartz, Robert S, Sealfon, Stuart C, Slentz, Cris, Sloan, Ruben, Smith, Kevin S, Snyder, Michael, Spahn, Jessica, Sparks, Lauren M, Stefanovic-Racic, Maja, Tanner, Charles J, Thalacker-Mercer, Anna, Tracy, Russell, Trappe, Todd A, Volpi, Elena, Walsh, Martin J, Wheeler, Matthew T, and Willis, Leslie

Subjects
Biomedical and Clinical Sciences, Health Sciences, Public Health, Sports Science and Exercise, Clinical Sciences, Behavioral and Social Science, Physical Activity, Nutrition, Clinical Research, Obesity, Prevention, Cardiovascular, 6.7 Physical, Generic health relevance, Good Health and Well Being, Humans, Exercise, Adult, Resistance Training, Child, Male, Female, Adolescent, Research Design, Cardiorespiratory Fitness, Muscle Strength, Body Composition, Young Adult, Endurance Training, adipose tissue, biospecimens, molecular transducers, physical activity, skeletal muscle, MoTrPAC Study Group, Biological Sciences, Medical and Health Sciences, Physiology, Biological sciences, Biomedical and clinical sciences, Health sciences
Abstract

Physical activity, including structured exercise, is associated with favorable health-related chronic disease outcomes. Although there is evidence of various molecular pathways that affect these responses, a comprehensive molecular map of these molecular responses to exercise has not been developed. The Molecular Transducers of Physical Activity Consortium (MoTrPAC) is a multicenter study designed to isolate the effects of structured exercise training on the molecular mechanisms underlying the health benefits of exercise and physical activity. MoTrPAC contains both a preclinical and human component. The details of the human studies component of MoTrPAC that include the design and methods are presented here. The human studies contain both an adult and pediatric component. In the adult component, sedentary participants are randomized to 12 wk of Control, Endurance Exercise Training, or Resistance Exercise Training with outcomes measures completed before and following the 12 wk. The adult component also includes recruitment of highly active endurance-trained or resistance-trained participants who only complete measures once. A similar design is used for the pediatric component; however, only endurance exercise is examined. Phenotyping measures include weight, body composition, vital signs, cardiorespiratory fitness, muscular strength, physical activity and diet, and other questionnaires. Participants also complete an acute rest period (adults only) or exercise session (adults, pediatrics) with collection of biospecimens (blood only for pediatrics) to allow for examination of the molecular responses. The design and methods of MoTrPAC may inform other studies. Moreover, MoTrPAC will provide a repository of data that can be used broadly across the scientific community.NEW & NOTEWORTHY The Molecular Transducers of Physical Activity Consortium (MoTrPAC) will be the first large trial to isolate the effects of structured exercise training on the molecular mechanisms underlying the health benefits of exercise and physical activity. By generating a compendium of the molecular responses to exercise, MoTrPAC will lay the foundation for a new era of biomedical research on Precision Exercise Medicine. Presented here is the design, protocols, and procedures for the MoTrPAC human studies.

Published
2024

2. Physiological Adaptations to Progressive Endurance Exercise Training in Adult and Aged Rats: Insights from the Molecular Transducers of Physical Activity Consortium (MoTrPAC)

Author

Schenk, Simon, Sagendorf, Tyler J, Many, Gina M, Lira, Ana K, de Sousa, Luis GO, Bae, Dam, Cicha, Michael, Kramer, Kyle S, Muehlbauer, Michael, Hevener, Andrea L, Rector, R Scott, Thyfault, John P, Williams, John P, Goodyear, Laurie J, Esser, Karyn A, Newgard, Christopher B, Bodine, Sue C, Adkins, Joshua N, Albertson, Brent G, Amar, David, Amper, Mary Anne S, Ashley, Euan, Bamman, Marcas M, Barnes, Jerry, Bergman, Bryan C, Bessesen, Daniel H, Buford, Thomas W, Burant, Charles F, Cutter, Gary R, De Sousa, Luis Gustavo Oliveria, Fernández, Facundo M, Gaul, David A, Ge, Yongchao, Goodpaster, Bret H, Guevara, Kristy, Hirshman, Michael F, Huffman, Kim M, Jackson, Bailey E, Jankowski, Catherine M, Jimenez-Morales, David, Kohrt, Wendy M, Kraus, William E, Lessard, Sarah J, Lester, Bridget, Lindholm, Malene E, Many, Gina, Marjanovic, Nada, Marshall, Andrea G, Melanson, Edward L, Miller, Michael E, Moreau, Kerrie L, Nair, Venugopalan D, Ortlund, Eric A, Qian, Wei-Jun, Rasmussen, Blake B, Richards, Collyn Z-T, Rushing, Scott, Sanford, James A, Schauer, Irene E, Schwartz, Robert S, Sealfon, Stuart C, Seenarine, Nitish, Sparks, Lauren M, Stowe, Cynthia L, Talton, Jennifer W, Teng, Christopher, Tesfa, Nathan D, Thalacker-Mercer, Anna, Trappe, Scott, Trappe, Todd A, Vasoya, Mital, Wheeler, Matthew T, Walkup, Michael P, Yan, Zhen, and Zhen, Jimmy

Subjects
Biomedical and Clinical Sciences, Clinical Sciences, Prevention, Cardiovascular, Physical Activity, Behavioral and Social Science, Animals, Male, Rats, Inbred F344, Female, Physical Conditioning, Animal, Adaptation, Physiological, Rats, Aging, Physical Endurance, Muscle, Skeletal, Endurance Training, training, treadmill, maximal oxygen uptake, body composition, citrate synthase, skeletal muscle, biorepository, aging, MoTrPAC Study Group, Medical physiology
Abstract

While regular physical activity is a cornerstone of health, wellness, and vitality, the impact of endurance exercise training on molecular signaling within and across tissues remains to be delineated. The Molecular Transducers of Physical Activity Consortium (MoTrPAC) was established to characterize molecular networks underlying the adaptive response to exercise. Here, we describe the endurance exercise training studies undertaken by the Preclinical Animal Sites Studies component of MoTrPAC, in which we sought to develop and implement a standardized endurance exercise protocol in a large cohort of rats. To this end, Adult (6-mo) and Aged (18-mo) female (n = 151) and male (n = 143) Fischer 344 rats were subjected to progressive treadmill training (5 d/wk, ∼70%-75% VO2max) for 1, 2, 4, or 8 wk; sedentary rats were studied as the control group. A total of 18 solid tissues, as well as blood, plasma, and feces, were collected to establish a publicly accessible biorepository and for extensive omics-based analyses by MoTrPAC. Treadmill training was highly effective, with robust improvements in skeletal muscle citrate synthase activity in as little as 1-2 wk and improvements in maximum run speed and maximal oxygen uptake by 4-8 wk. For body mass and composition, notable age- and sex-dependent responses were observed. This work in mature, treadmill-trained rats represents the most comprehensive and publicly accessible tissue biorepository, to date, and provides an unprecedented resource for studying temporal-, sex-, and age-specific responses to endurance exercise training in a preclinical rat model.

Published
2024

3. Temporal dynamics of the multi-omic response to endurance exercise training

Author

Bae, Dam, Dasari, Surendra, Dennis, Courtney, Evans, Charles R, Gaul, David A, Ilkayeva, Olga, Ivanova, Anna A, Kachman, Maureen T, Keshishian, Hasmik, Lanza, Ian R, Lira, Ana C, Muehlbauer, Michael J, Nair, Venugopalan D, Piehowski, Paul D, Rooney, Jessica L, Smith, Kevin S, Stowe, Cynthia L, Zhao, Bingqing, Clark, Natalie M, Jimenez-Morales, David, Lindholm, Malene E, Many, Gina M, Sanford, James A, Smith, Gregory R, Vetr, Nikolai G, Zhang, Tiantian, Almagro Armenteros, Jose J, Avila-Pacheco, Julian, Bararpour, Nasim, Ge, Yongchao, Hou, Zhenxin, Marwaha, Shruti, Presby, David M, Natarajan Raja, Archana, Savage, Evan M, Steep, Alec, Sun, Yifei, Wu, Si, Zhen, Jimmy, Bodine, Sue C, Esser, Karyn A, Goodyear, Laurie J, Schenk, Simon, Montgomery, Stephen B, Fernández, Facundo M, Sealfon, Stuart C, Snyder, Michael P, Adkins, Joshua N, Ashley, Euan, Burant, Charles F, Carr, Steven A, Clish, Clary B, Cutter, Gary, Gerszten, Robert E, Kraus, William E, Li, Jun Z, Miller, Michael E, Nair, K Sreekumaran, Newgard, Christopher, Ortlund, Eric A, Qian, Wei-Jun, Tracy, Russell, Walsh, Martin J, Wheeler, Matthew T, Dalton, Karen P, Hastie, Trevor, Hershman, Steven G, Samdarshi, Mihir, Teng, Christopher, Tibshirani, Rob, Cornell, Elaine, Gagne, Nicole, May, Sandy, Bouverat, Brian, Leeuwenburgh, Christiaan, Lu, Ching-ju, Pahor, Marco, Hsu, Fang-Chi, Rushing, Scott, Walkup, Michael P, Nicklas, Barbara, Rejeski, W Jack, Williams, John P, Xia, Ashley, Albertson, Brent G, Barton, Elisabeth R, Booth, Frank W, Caputo, Tiziana, Cicha, Michael, De Sousa, Luis Gustavo Oliveira, Farrar, Roger, Hevener, Andrea L, Hirshman, Michael F, Jackson, Bailey E, Ke, Benjamin G, Kramer, Kyle S, Lessard, Sarah J, Makarewicz, Nathan S, Marshall, Andrea G, and Nigro, Pasquale

Subjects
Health Sciences, Sports Science and Exercise, Genetics, Prevention, Human Genome, Cardiovascular, Physical Activity, Behavioral and Social Science, 2.1 Biological and endogenous factors, 1.1 Normal biological development and functioning, Inflammatory and immune system, Generic health relevance, Good Health and Well Being, Animals, Female, Humans, Male, Rats, Acetylation, Blood, Cardiovascular Diseases, Databases, Factual, Endurance Training, Epigenome, Inflammatory Bowel Diseases, Internet, Lipidomics, Metabolome, Mitochondria, Multiomics, Non-alcoholic Fatty Liver Disease, Organ Specificity, Phosphorylation, Physical Conditioning, Animal, Physical Endurance, Proteome, Proteomics, Time Factors, Transcriptome, Ubiquitination, Wounds and Injuries, MoTrPAC Study Group, Lead Analysts, MoTrPAC Study Group, General Science & Technology
Abstract

Regular exercise promotes whole-body health and prevents disease, but the underlying molecular mechanisms are incompletely understood1-3. Here, the Molecular Transducers of Physical Activity Consortium4 profiled the temporal transcriptome, proteome, metabolome, lipidome, phosphoproteome, acetylproteome, ubiquitylproteome, epigenome and immunome in whole blood, plasma and 18 solid tissues in male and female Rattus norvegicus over eight weeks of endurance exercise training. The resulting data compendium encompasses 9,466 assays across 19 tissues, 25 molecular platforms and 4 training time points. Thousands of shared and tissue-specific molecular alterations were identified, with sex differences found in multiple tissues. Temporal multi-omic and multi-tissue analyses revealed expansive biological insights into the adaptive responses to endurance training, including widespread regulation of immune, metabolic, stress response and mitochondrial pathways. Many changes were relevant to human health, including non-alcoholic fatty liver disease, inflammatory bowel disease, cardiovascular health and tissue injury and recovery. The data and analyses presented in this study will serve as valuable resources for understanding and exploring the multi-tissue molecular effects of endurance training and are provided in a public repository ( https://motrpac-data.org/ ).

Published
2024

4. Sexual dimorphism and the multi-omic response to exercise training in rat subcutaneous white adipose tissue

Author

Many, Gina M, Sanford, James A, Sagendorf, Tyler J, Hou, Zhenxin, Nigro, Pasquale, Whytock, Katie L, Amar, David, Caputo, Tiziana, Gay, Nicole R, Gaul, David A, Hirshman, Michael F, Jimenez-Morales, David, Lindholm, Malene E, Muehlbauer, Michael J, Vamvini, Maria, Bergman, Bryan C, Fernández, Facundo M, Goodyear, Laurie J, Hevener, Andrea L, Ortlund, Eric A, Sparks, Lauren M, Xia, Ashley, Adkins, Joshua N, Bodine, Sue C, Newgard, Christopher B, and Schenk, Simon

Subjects
Medical Biochemistry and Metabolomics, Medical Physiology, Biomedical and Clinical Sciences, Nutrition and Dietetics, Behavioral and Social Science, Women's Health, Prevention, Physical Activity, Animals, Male, Female, Physical Conditioning, Animal, Rats, Sex Characteristics, Adipose Tissue, White, Subcutaneous Fat, Adipogenesis, Rats, Sprague-Dawley, Multiomics, MoTrPAC Study Group, Medical biochemistry and metabolomics, Medical physiology, Nutrition and dietetics
Abstract

Subcutaneous white adipose tissue (scWAT) is a dynamic storage and secretory organ that regulates systemic homeostasis, yet the impact of endurance exercise training (ExT) and sex on its molecular landscape is not fully established. Utilizing an integrative multi-omics approach, and leveraging data generated by the Molecular Transducers of Physical Activity Consortium (MoTrPAC), we show profound sexual dimorphism in the scWAT of sedentary rats and in the dynamic response of this tissue to ExT. Specifically, the scWAT of sedentary females displays -omic signatures related to insulin signaling and adipogenesis, whereas the scWAT of sedentary males is enriched in terms related to aerobic metabolism. These sex-specific -omic signatures are preserved or amplified with ExT. Integration of multi-omic analyses with phenotypic measures identifies molecular hubs predicted to drive sexually distinct responses to training. Overall, this study underscores the powerful impact of sex on adipose tissue biology and provides a rich resource to investigate the scWAT response to ExT.

Published
2024

5. Decoding the Molecular Universe -- Workshop Report

Author

Metz, Thomas O., Adkins, Joshua N., Armentrout, Peter B., Chain, Patrick, Chu, Fanny, Corley, Courtney D, Cort, John R., Denis, Elizabeth, Drell, Daniel, Duncan, Katherine R., Ewing, Robert G., Fernandez, Facundo M., Fiehn, Oliver, Garg, Neha, Grimme, Stefan, Henry, Christopher, Hettich, Robert L., Kind, Tobias, Linington, Roger G., Miller, Gary W., Northen, Trent, Overdahl, Kirsten, Patrinos, Ari, Raftery, Daniel, Rigor, Paul, Smith, Richard D., Sobus, Jon, Teeguarden, Justin, Vertes, Akos, Waters, Katrina, Webb-Robertson, Bobbie-Jo, Williams, Antony, and Wishart, David

Subjects
Quantitative Biology - Biomolecules
Abstract

On August 9-10, 2023, a workshop was convened at the Pacific Northwest National Laboratory (PNNL) in Richland, WA that brought together a group of internationally recognized experts in metabolomics, natural products discovery, chemical ecology, chemical and biological threat assessment, cheminformatics, computational chemistry, cloud computing, artificial intelligence, and novel technology development. These experts were invited to assess the value and feasibility of a grand-scale project to create new technologies that would allow the identification and quantification of all small molecules, or to decode the molecular universe. The Decoding the Molecular Universe project would extend and complement the success of the Human Genome Project by developing new capabilities and technologies to measure small molecules (defined as non-protein, non-polymer molecules less than 1500 Daltons) of any origin and generated in biological systems or produced abiotically. Workshop attendees 1) explored what new understanding of biological and environmental systems could be revealed through the lens of small molecules; 2) characterized the similarities in current needs and technical challenges between each science or mission area for unambiguous and comprehensive determination of the composition and quantities of small molecules of any sample; 3) determined the extent to which technologies or methods currently exist for unambiguously and comprehensively determining the small molecule composition of any sample and in a reasonable time; and 4) identified the attributes of the ideal technology or approach for universal small molecule measurement and identification. The workshop concluded with a discussion of how a project of this scale could be undertaken, possible thrusts for the project, early proof-of-principle applications, and similar efforts upon which the project could be modeled.

Published
2023

6. Molecular adaptations in response to exercise training are associated with tissue-specific transcriptomic and epigenomic signatures

Author

Adkins, Joshua N., Almagro Armenteros, Jose Juan, Ashley, Euan, Bae, Dam, Bamman, Marcas, Bararpour, Nasim, Bennett, Alexis, Bergman, Bryan C., Bessesen, Daniel H., Bodine, Sue C., Buford, Thomas W., Chambers, Toby L., Chavez, Clarisa, Cortes, Tiffany, Cutter, Gary, Espinoza, Sara, Fernández, Facundo M., Gagne, Nicole, Gaul, David A., Goodpaster, Bret H., Hung, Chia-Jui, Jackson, Bailey E., Jankowski, Catherine M., Jin, Christopher A., Kohrt, Wendy M., Kramer, Kyle S., Lester, Bridget, Lira, Ana K., May, Sandy, Marjanovic, Nada, Melanson, Edward L., Moore, Samuel G., Moreau, Kerrie L., Musi, Nicolas, Nachum, Daniel, Nudelman, German, Pahor, Marco, Patel, Darpan, Piehowski, Paul D., Qian, Wei-Jun, Rasmussen, Blake B., Rirak, Stas, Rooney, Jessica L., Sanford, James A., Savage, Evan M., Schauer, Irene E., Serra, Monica, Stowe, Cynthia L., Thalacker-Mercer, Anna, Trappe, Todd A., Trappe, Scott, Vetr, Nikolai G., Volpi, Elena, Wheeler, Matthew T., Wu, Si, Zebarjadi, Navid, Zhen, Jimmy, Nair, Venugopalan D., Pincas, Hanna, Smith, Gregory R., Zaslavsky, Elena, Ge, Yongchao, Amper, Mary Anne S., Vasoya, Mital, Chikina, Maria, Sun, Yifei, Raja, Archana Natarajan, Mao, Weiguang, Gay, Nicole R., Esser, Karyn A., Smith, Kevin S., Zhao, Bingqing, Wiel, Laurens, Singh, Aditya, Lindholm, Malene E., Amar, David, Montgomery, Stephen, Snyder, Michael P., Walsh, Martin J., and Sealfon, Stuart C.

Published
2024
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7. The mitochondrial multi-omic response to exercise training across rat tissues

Author

Adkins, Joshua N., Armenteros, Jose Juan Almagro, Amper, Mary Anne S., Bae, Dam, Bamman, Marcas, Bararpour, Nasim, Barnes, Jerry, Bergman, Bryan C., Bessesen, Daniel H., Broskey, Nicholas T., Buford, Thomas W., Carr, Steven, Chambers, Toby L., Chavez, Clarisa, Chiu, Roxanne, Clark, Natalie, Cutter, Gary, Evans, Charles R., Franczak, Edziu, Gagne, Nicole, Ge, Yongchao, Hennig, Krista M., Houmard, Joseph A., Huffman, Kim M., Hung, Chia-Jui, Hutchinson-Bunch, Chelsea, Ilkayeva, Olga, Jackson, Bailey E., Jankowski, Catherine M., Jin, Christopher A., Johannsen, Neil M., Katz, Daniel H., Keshishian, Hasmik, Kohrt, Wendy M., Kramer, Kyle S., Kraus, William E., Lester, Bridget, Li, Jun Z., Lira, Ana K., Lowe, Adam, Mani, D.R., Many, Gina M., May, Sandy, Melanson, Edward L., Moore, Samuel G., Moreau, Kerrie L., Musi, Nicolas, Nachun, Daniel, Nair, Venugopalan D., Newgard, Christopher, Nudelman, German, Piehowski, Paul D., Pincas, Hanna, Qian, Wei-Jun, Rankinen, Tuomo, Rasmussen, Blake B., Ravussin, Eric, Rooney, Jessica L., Rushing, Scott, Samdarshi, Mihir, Sanford, James A., Schauer, Irene E., Sealfon, Stuart C., Smith, Kevin S., Smith, Gregory R., Snyder, Michael, Stowe, Cynthia L., Talton, Jennifer W., Teng, Christopher, Thalacker-Mercer, Anna, Tracy, Russell, Trappe, Scott, Trappe, Todd A., Vasoya, Mital, Vetr, Nikolai G., Volpi, Elena, Walkup, Michael P., Wiel, Laurens, Wu, Si, Yan, Zhen, Yu, Jiye, Zaslavsky, Elena, Zebarjadi, Navid, Zhen, Jimmy, Amar, David, Gay, Nicole R., Jimenez-Morales, David, Jean Beltran, Pierre M., Ramaker, Megan E., Raja, Archana Natarajan, Zhao, Bingqing, Sun, Yifei, Marwaha, Shruti, Gaul, David A., Hershman, Steven G., Ferrasse, Alexis, Xia, Ashley, Lanza, Ian, Fernández, Facundo M., Montgomery, Stephen B., Hevener, Andrea L., Ashley, Euan A., Walsh, Martin J., Sparks, Lauren M., Burant, Charles F., Rector, R. Scott, Thyfault, John, Wheeler, Matthew T., Goodpaster, Bret H., Coen, Paul M., Schenk, Simon, Bodine, Sue C., and Lindholm, Malene E.

Published
2024
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8. Guided construction of single cell reference for human and mouse lung

Author

Guo, Minzhe, Morley, Michael P., Jiang, Cheng, Wu, Yixin, Li, Guangyuan, Du, Yina, Zhao, Shuyang, Wagner, Andrew, Cakar, Adnan Cihan, Kouril, Michal, Jin, Kang, Gaddis, Nathan, Kitzmiller, Joseph A., Stewart, Kathleen, Basil, Maria C., Lin, Susan M., Ying, Yun, Babu, Apoorva, Wikenheiser-Brokamp, Kathryn A., Mun, Kyu Shik, Naren, Anjaparavanda P., Clair, Geremy, Adkins, Joshua N., Pryhuber, Gloria S., Misra, Ravi S., Aronow, Bruce J., Tickle, Timothy L., Salomonis, Nathan, Sun, Xin, Morrisey, Edward E., Whitsett, Jeffrey A., and Xu, Yan

Published
2023
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9. efam: an expanded, metaproteome-supported HMM profile database of viral protein families

Author

Zayed, Ahmed A, Lücking, Dominik, Mohssen, Mohamed, Cronin, Dylan, Bolduc, Ben, Gregory, Ann C, Hargreaves, Katherine R, Piehowski, Paul D, White Iii, Richard A, Huang, Eric L, Adkins, Joshua N, Roux, Simon, Moraru, Cristina, and Sullivan, Matthew B

Subjects
Genetics, Infection, Animals, Viral Proteins, Software, Metagenomics, Viruses, Microbiota, Mathematical Sciences, Biological Sciences, Information and Computing Sciences, Bioinformatics
Abstract

MotivationViruses infect, reprogram and kill microbes, leading to profound ecosystem consequences, from elemental cycling in oceans and soils to microbiome-modulated diseases in plants and animals. Although metagenomic datasets are increasingly available, identifying viruses in them is challenging due to poor representation and annotation of viral sequences in databases.ResultsHere, we establish efam, an expanded collection of Hidden Markov Model (HMM) profiles that represent viral protein families conservatively identified from the Global Ocean Virome 2.0 dataset. This resulted in 240 311 HMM profiles, each with at least 2 protein sequences, making efam >7-fold larger than the next largest, pan-ecosystem viral HMM profile database. Adjusting the criteria for viral contig confidence from 'conservative' to 'eXtremely Conservative' resulted in 37 841 HMM profiles in our efam-XC database. To assess the value of this resource, we integrated efam-XC into VirSorter viral discovery software to discover viruses from less-studied, ecologically distinct oxygen minimum zone (OMZ) marine habitats. This expanded database led to an increase in viruses recovered from every tested OMZ virome by ∼24% on average (up to ∼42%) and especially improved the recovery of often-missed shorter contigs (

Published
2021

10. Molecular Transducers of Physical Activity Consortium (MoTrPAC): Mapping the Dynamic Responses to Exercise

Author

Sanford, James A, Nogiec, Christopher D, Lindholm, Malene E, Adkins, Joshua N, Amar, David, Dasari, Surendra, Drugan, Jonelle K, Fernández, Facundo M, Radom-Aizik, Shlomit, Schenk, Simon, Snyder, Michael P, Tracy, Russell P, Vanderboom, Patrick, Trappe, Scott, Walsh, Martin J, Consortium, the Molecular Transducers of Physical Activity, Evans, Charles R, Fernandez, Facundo M, Li, Yafeng, Tomlinson, Lyl, Alekel, D Lee, Bekirov, Iddil, Boyce, Amanda T, Boyington, Josephine, Fleg, Jerome L, Joseph, Lyndon JO, Laughlin, Maren R, Maruvada, Padma, Morris, Stephanie A, McGowan, Joan A, Nierras, Concepcion, Pai, Vinay, Peterson, Charlotte, Ramos, Ed, Roary, Mary C, Williams, John P, Xia, Ashley, Cornell, Elaine, Rooney, Jessica, Miller, Michael E, Ambrosius, Walter T, Rushing, Scott, Stowe, Cynthia L, Rejeski, W Jack, Nicklas, Barbara J, Pahor, Marco, Lu, Ching-ju, Trappe, Todd, Chambers, Toby, Raue, Ulrika, Lester, Bridget, Bergman, Bryan C, Bessesen, David H, Jankowski, Catherine M, Kohrt, Wendy M, Melanson, Edward L, Moreau, Kerrie L, Schauer, Irene E, Schwartz, Robert S, Kraus, William E, Slentz, Cris A, Huffman, Kim M, Johnson, Johanna L, Willis, Leslie H, Kelly, Leslie, Houmard, Joseph A, Dubis, Gabriel, Broskey, Nick, Goodpaster, Bret H, Sparks, Lauren M, Coen, Paul M, Cooper, Dan M, Haddad, Fadia, Rankinen, Tuomo, Ravussin, Eric, Johannsen, Neil, Harris, Melissa, Jakicic, John M, Newman, Anne B, Forman, Daniel D, Kershaw, Erin, Rogers, Renee J, Nindl, Bradley C, Page, Lindsay C, Stefanovic-Racic, Maja, and Barr, Susan L

Subjects
Biomedical and Clinical Sciences, Clinical Sciences, Prevention, Physical Activity, Cardiovascular, Behavioral and Social Science, Generic health relevance, Good Health and Well Being, Adolescent, Adult, Animals, Child, Exercise, Female, Humans, Male, Middle Aged, Oxygen Consumption, Physical Endurance, Research Design, Young Adult, Molecular Transducers of Physical Activity Consortium, Biological Sciences, Medical and Health Sciences, Developmental Biology, Biological sciences, Biomedical and clinical sciences
Abstract

Exercise provides a robust physiological stimulus that evokes cross-talk among multiple tissues that when repeated regularly (i.e., training) improves physiological capacity, benefits numerous organ systems, and decreases the risk for premature mortality. However, a gap remains in identifying the detailed molecular signals induced by exercise that benefits health and prevents disease. The Molecular Transducers of Physical Activity Consortium (MoTrPAC) was established to address this gap and generate a molecular map of exercise. Preclinical and clinical studies will examine the systemic effects of endurance and resistance exercise across a range of ages and fitness levels by molecular probing of multiple tissues before and after acute and chronic exercise. From this multi-omic and bioinformatic analysis, a molecular map of exercise will be established. Altogether, MoTrPAC will provide a public database that is expected to enhance our understanding of the health benefits of exercise and to provide insight into how physical activity mitigates disease.

Published
2020

11. Lignin induced iron reduction by novel sp., Tolumonas lignolytic BRL6-1

Author

Chaput, Gina, Billings, Andrew F, DeDiego, Lani, Orellana, Roberto, Adkins, Joshua N, Nicora, Carrie D, Kim, Young-Mo, Chu, Rosalie, Simmons, Blake, and DeAngelis, Kristen M

Subjects
Biochemistry and Cell Biology, Biological Sciences, Aeromonadaceae, Bacterial Proteins, Biomass, Iron, Lignin, Oxidation-Reduction, Sulfatases, General Science & Technology
Abstract

Lignin is the second most abundant carbon polymer on earth and despite having more fuel value than cellulose, it currently is considered a waste byproduct in many industrial lignocellulose applications. Valorization of lignin relies on effective and green methods of de-lignification, with a growing interest in the use of microbes. Here we investigate the physiology and molecular response of the novel facultative anaerobic bacterium, Tolumonas lignolytica BRL6-1, to lignin under anoxic conditions. Physiological and biochemical changes were compared between cells grown anaerobically in either lignin-amended or unamended conditions. In the presence of lignin, BRL6-1 accumulates higher biomass and has a shorter lag phase compared to unamended conditions, and 14% of the proteins determined to be significantly higher in abundance by log2 fold-change of 2 or greater were related to Fe(II) transport in late logarithmic phase. Ferrozine assays of the supernatant confirmed that Fe(III) was bound to lignin and reduced to Fe(II) only in the presence of BRL6-1, suggesting redox activity by the cells. LC-MS/MS analysis of the secretome showed an extra band at 20 kDa in lignin-amended conditions. Protein sequencing of this band identified a protein of unknown function with homology to enzymes in the radical SAM superfamily. Expression of this protein in lignin-amended conditions suggests its role in radical formation. From our findings, we suggest that BRL6-1 is using a protein in the radical SAM superfamily to interact with the Fe(III) bound to lignin and reducing it to Fe(II) for cellular use, increasing BRL6-1 yield under lignin-amended conditions. This interaction potentially generates organic free radicals and causes a radical cascade which could modify and depolymerize lignin. Further research should clarify the extent to which this mechanism is similar to previously described aerobic chelator-mediated Fenton chemistry or radical producing lignolytic enzymes, such as lignin peroxidases, but under anoxic conditions.

Published
2020

12. Gut anatomical properties and microbial functional assembly promote lignocellulose deconstruction and colony subsistence of a wood-feeding beetle.

Author

Ceja-Navarro, Javier A, Karaoz, Ulas, Bill, Markus, Hao, Zhao, White, Richard A, Arellano, Abelardo, Ramanculova, Leila, Filley, Timothy R, Berry, Timothy D, Conrad, Mark E, Blackwell, Meredith, Nicora, Carrie D, Kim, Young-Mo, Reardon, Patrick N, Lipton, Mary S, Adkins, Joshua N, Pett-Ridge, Jennifer, and Brodie, Eoin L

Subjects
Gastrointestinal Tract, Animals, Bacteria, Oxygen, Hydrogen, Lignin, Phylogeny, Fermentation, Wood, Gastrointestinal Microbiome, Coleoptera, Nutrition, Microbiology, Medical Microbiology
Abstract

Beneficial microbial associations enhance the fitness of most living organisms, and wood-feeding insects offer some of the most striking examples of this. Odontotaenius disjunctus is a wood-feeding beetle that possesses a digestive tract with four main compartments, each of which contains well-differentiated microbial populations, suggesting that anatomical properties and separation of these compartments may enhance energy extraction from woody biomass. Here, using integrated chemical analyses, we demonstrate that lignocellulose deconstruction and fermentation occur sequentially across compartments, and that selection for microbial groups and their metabolic pathways is facilitated by gut anatomical features. Metaproteogenomics showed that higher oxygen concentration in the midgut drives lignocellulose depolymerization, while a thicker gut wall in the anterior hindgut reduces oxygen diffusion and favours hydrogen accumulation, facilitating fermentation, homoacetogenesis and nitrogen fixation. We demonstrate that depolymerization continues in the posterior hindgut, and that the beetle excretes an energy- and nutrient-rich product on which its offspring subsist and develop. Our results show that the establishment of beneficial microbial partners within a host requires both the acquisition of the microorganisms and the formation of specific habitats within the host to promote key microbial metabolic functions. Together, gut anatomical properties and microbial functional assembly enable lignocellulose deconstruction and colony subsistence on an extremely nutrient-poor diet.

Published
2019

13. Molecular Transducers of Physical Activity Consortium (MoTrPAC): Mapping the Dynamic Responses to Exercise

Author

Adkins, Joshua N., Amar, David, Dasari, Surendra, Drugan, Jonelle K., Evans, Charles R., Fernandez, Facundo M., Li, Yafeng, Lindholm, Malene E., Nogiec, Christopher D., Radom-Aizik, Shlomit, Sanford, James A., Schenk, Simon, Snyder, Michael P., Tomlinson, Lyl, Tracy, Russell P., Trappe, Scott, Vanderboom, Patrick, Walsh, Martin J., Lee Alekel, D., Bekirov, Iddil, Boyce, Amanda T., Boyington, Josephine, Fleg, Jerome L., Joseph, Lyndon J.O., Laughlin, Maren R., Maruvada, Padma, Morris, Stephanie A., McGowan, Joan A., Nierras, Concepcion, Pai, Vinay, Peterson, Charlotte, Ramos, Ed, Roary, Mary C., Williams, John P., Xia, Ashley, Cornell, Elaine, Rooney, Jessica, Miller, Michael E., Ambrosius, Walter T., Rushing, Scott, Stowe, Cynthia L., Jack Rejeski, W., Nicklas, Barbara J., Pahor, Marco, Lu, Ching-ju, Trappe, Todd, Chambers, Toby, Raue, Ulrika, Lester, Bridget, Bergman, Bryan C., Bessesen, David H., Jankowski, Catherine M., Kohrt, Wendy M., Melanson, Edward L., Moreau, Kerrie L., Schauer, Irene E., Schwartz, Robert S., Kraus, William E., Slentz, Cris A., Huffman, Kim M., Johnson, Johanna L., Willis, Leslie H., Kelly, Leslie, Houmard, Joseph A., Dubis, Gabriel, Broskey, Nick, Goodpaster, Bret H., Sparks, Lauren M., Coen, Paul M., Cooper, Dan M., Haddad, Fadia, Rankinen, Tuomo, Ravussin, Eric, Johannsen, Neil, Harris, Melissa, Jakicic, John M., Newman, Anne B., Forman, Daniel D., Kershaw, Erin, Rogers, Renee J., Nindl, Bradley C., Page, Lindsay C., Stefanovic-Racic, Maja, Barr, Susan L., Rasmussen, Blake B., Moro, Tatiana, Paddon-Jones, Doug, Volpi, Elena, Spratt, Heidi, Musi, Nicolas, Espinoza, Sara, Patel, Darpan, Serra, Monica, Gelfond, Jonathan, Burns, Aisling, Bamman, Marcas M., Buford, Thomas W., Cutter, Gary R., Bodine, Sue C., Esser, Karyn, Farrar, Rodger P., Goodyear, Laurie J., Hirshman, Michael F., Albertson, Brent G., Qian, Wei-Jun, Piehowski, Paul, Gritsenko, Marina A., Monore, Matthew E., Petyuk, Vladislav A., McDermott, Jason E., Hansen, Joshua N., Hutchison, Chelsea, Moore, Samuel, Gaul, David A., Clish, Clary B., Avila-Pacheco, Julian, Dennis, Courtney, Kellis, Manolis, Carr, Steve, Jean-Beltran, Pierre M., Keshishian, Hasmik, Mani, D.R., Clauser, Karl, Krug, Karsten, Mundorff, Charlie, Pearce, Cadence, Ivanova, Anna A., Ortlund, Eric A., Maner-Smith, Kristal, Uppal, Karan, Zhang, Tiantian, Sealfon, Stuart C., Zaslavsky, Elena, Nair, Venugopalan, Li, SiDe, Jain, Nimisha, Ge, YongChao, Sun, Yifei, Nudelman, German, Ruf-zamojski, Frederique, Smith, Gregory, Pincas, Nhanna, Rubenstein, Aliza, Anne Amper, Mary, Seenarine, Nitish, Lappalainen, Tuuli, Lanza, Ian R., Sreekumaran Nair, K., Klaus, Katherine, Montgomery, Stephen B., Smith, Kevin S., Gay, Nicole R., Zhao, Bingqing, Hung, Chia-Jiu, Zebarjadi, Navid, Balliu, Brunilda, Fresard, Laure, Burant, Charles F., Li, Jun Z., Kachman, Maureen, Soni, Tanu, Raskind, Alexander B., Gerszten, Robert, Robbins, Jeremy, Ilkayeva, Olga, Muehlbauer, Michael J., Newgard, Christopher B., Ashley, Euan A., Wheeler, Matthew T., Jimenez-Morales, David, Raja, Archana, Dalton, Karen P., Zhen, Jimmy, Suk Kim, Young, Christle, Jeffrey W., Marwaha, Shruti, Chin, Elizabeth T., Hershman, Steven G., Hastie, Trevor, Tibshirani, Robert, Rivas, Manuel A., and Fernández, Facundo M.

Published
2020
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14. Environment-specific virocell metabolic reprogramming

Author

Howard-Varona, Cristina, primary, Lindback, Morgan M, additional, Fudyma, Jane D, additional, Krongauz, Azriel, additional, Solonenko, Natalie E, additional, Zayed, Ahmed A, additional, Andreopoulos, William B, additional, Olson, Heather M, additional, Kim, Young-Mo, additional, Kyle, Jennifer E, additional, del Rio, Tijana Glavina, additional, Adkins, Joshua N, additional, Tfaily, Malak M, additional, Paul, Subhadeep, additional, Sullivan, Matthew B, additional, and Duhaime, Melissa B, additional

Published
2024
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15. Phage-specific metabolic reprogramming of virocells

Author

Howard-Varona, Cristina, Lindback, Morgan M., Bastien, G. Eric, Solonenko, Natalie, Zayed, Ahmed A., Jang, HoBin, Andreopoulos, Bill, Brewer, Heather M., Glavina del Rio, Tijana, Adkins, Joshua N., Paul, Subhadeep, Sullivan, Matthew B., and Duhaime, Melissa B.

Published
2020
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16. Multicopy Single-Stranded DNA Directs Intestinal Colonization of Enteric Pathogens.

Author

Elfenbein, Johanna R, Knodler, Leigh A, Nakayasu, Ernesto S, Ansong, Charles, Brewer, Heather M, Bogomolnaya, Lydia, Adams, L Garry, McClelland, Michael, Adkins, Joshua N, and Andrews-Polymenis, Helene L

Subjects
Intestines, Animals, Mice, Escherichia coli, Salmonella typhimurium, DNA, Single-Stranded, Anaerobiosis, Developmental Biology, Genetics
Abstract

Multicopy single-stranded DNAs (msDNAs) are hybrid RNA-DNA molecules encoded on retroelements called retrons and produced by the action of retron reverse transcriptases. Retrons are widespread in bacteria but the natural function of msDNA has remained elusive despite 30 years of study. The major roadblock to elucidation of the function of these unique molecules has been the lack of any identifiable phenotypes for mutants unable to make msDNA. We report that msDNA of the zoonotic pathogen Salmonella Typhimurium is necessary for colonization of the intestine. Similarly, we observed a defect in intestinal persistence in an enteropathogenic E. coli mutant lacking its retron reverse transcriptase. Under anaerobic conditions in the absence of msDNA, proteins of central anaerobic metabolism needed for Salmonella colonization of the intestine are dysregulated. We show that the msDNA-deficient mutant can utilize nitrate, but not other alternate electron acceptors in anaerobic conditions. Consistent with the availability of nitrate in the inflamed gut, a neutrophilic inflammatory response partially rescued the ability of a mutant lacking msDNA to colonize the intestine. These findings together indicate that the mechanistic basis of msDNA function during Salmonella colonization of the intestine is proper production of proteins needed for anaerobic metabolism. We further conclude that a natural function of msDNA is to regulate protein abundance, the first attributable function for any msDNA. Our data provide novel insight into the function of this mysterious molecule that likely represents a new class of regulatory molecules.

Published
2015

20. Viral afterlife: SARS-CoV-2 as a reservoir of immunomimetic peptides that reassemble into proinflammatory supramolecular complexes

Author

Zhang, Yue, primary, Bharathi, Vanthana, additional, Dokoshi, Tatsuya, additional, de Anda, Jaime, additional, Ursery, Lauryn Tumey, additional, Kulkarni, Nikhil N., additional, Nakamura, Yoshiyuki, additional, Chen, Jonathan, additional, Luo, Elizabeth W. C., additional, Wang, Lamei, additional, Xu, Hua, additional, Coady, Alison, additional, Zurich, Raymond, additional, Lee, Michelle W., additional, Matsui, Tsutomu, additional, Lee, HongKyu, additional, Chan, Liana C., additional, Schepmoes, Athena A., additional, Lipton, Mary S., additional, Zhao, Rui, additional, Adkins, Joshua N., additional, Clair, Geremy C., additional, Thurlow, Lance R., additional, Schisler, Jonathan C., additional, Wolfgang, Matthew C., additional, Hagan, Robert S., additional, Yeaman, Michael R., additional, Weiss, Thomas M., additional, Chen, Xinhua, additional, Li, Melody M. H., additional, Nizet, Victor, additional, Antoniak, Silvio, additional, Mackman, Nigel, additional, Gallo, Richard L., additional, and Wong, Gerard C. L., additional

Published
2024
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22. Experimental annotation of post-translational features and translated coding regions in the pathogen Salmonella Typhimurium

Author

Ansong, Charles, Tolić, Nikola, Purvine, Samuel O, Porwollik, Steffen, Jones, Marcus, Yoon, Hyunjin, Payne, Samuel H, Martin, Jessica L, Burnet, Meagan C, Monroe, Matthew E, Venepally, Pratap, Smith, Richard D, Peterson, Scott N, Heffron, Fred, McClelland, Michael, and Adkins, Joshua N

Subjects
Microbiology, Biological Sciences, Bioinformatics and Computational Biology, Emerging Infectious Diseases, Infectious Diseases, Genetics, Biotechnology, 2.2 Factors relating to the physical environment, 2.1 Biological and endogenous factors, Infection, Chromatography, Liquid, Genome, Bacterial, Molecular Sequence Annotation, Open Reading Frames, Protein Processing, Post-Translational, Proteolysis, Proteome, Proteomics, Salmonella typhimurium, Tandem Mass Spectrometry, gene annotation, proteomics, post-translational modifications, Information and Computing Sciences, Medical and Health Sciences, Bioinformatics, Biological sciences, Biomedical and clinical sciences
Abstract

BackgroundComplete and accurate genome annotation is crucial for comprehensive and systematic studies of biological systems. However, determining protein-coding genes for most new genomes is almost completely performed by inference using computational predictions with significant documented error rates (> 15%). Furthermore, gene prediction programs provide no information on biologically important post-translational processing events critical for protein function.ResultsWe experimentally annotated the bacterial pathogen Salmonella Typhimurium 14028, using "shotgun" proteomics to accurately uncover the translational landscape and post-translational features. The data provide protein-level experimental validation for approximately half of the predicted protein-coding genes in Salmonella and suggest revisions to several genes that appear to have incorrectly assigned translational start sites, including a potential novel alternate start codon. Additionally, we uncovered 12 non-annotated genes missed by gene prediction programs, as well as evidence suggesting a role for one of these novel ORFs in Salmonella pathogenesis. We also characterized post-translational features in the Salmonella genome, including chemical modifications and proteolytic cleavages. We find that bacteria have a much larger and more complex repertoire of chemical modifications than previously thought including several novel modifications. Our in vivo proteolysis data identified more than 130 signal peptide and N-terminal methionine cleavage events critical for protein function.ConclusionThis work highlights several ways in which application of proteomics data can improve the quality of genome annotations to facilitate novel biological insights and provides a comprehensive proteome map of Salmonella as a resource for systems analysis.

Published
2011

23. An experimentally-supported genome-scale metabolic network reconstruction for Yersinia pestis CO92

Author

Charusanti, Pep, Chauhan, Sadhana, McAteer, Kathleen, Lerman, Joshua A, Hyduke, Daniel R, Motin, Vladimir L, Ansong, Charles, Adkins, Joshua N, and Palsson, Bernhard O

Abstract

Abstract Background Yersinia pestis is a gram-negative bacterium that causes plague, a disease linked historically to the Black Death in Europe during the Middle Ages and to several outbreaks during the modern era. Metabolism in Y. pestis displays remarkable flexibility and robustness, allowing the bacterium to proliferate in both warm-blooded mammalian hosts and cold-blooded insect vectors such as fleas. Results Here we report a genome-scale reconstruction and mathematical model of metabolism for Y. pestis CO92 and supporting experimental growth and metabolite measurements. The model contains 815 genes, 678 proteins, 963 unique metabolites and 1678 reactions, accurately simulates growth on a range of carbon sources both qualitatively and quantitatively, and identifies gaps in several key biosynthetic pathways and suggests how those gaps might be filled. Furthermore, our model presents hypotheses to explain certain known nutritional requirements characteristic of this strain. Conclusions Y. pestis continues to be a dangerous threat to human health during modern times. The Y. pestis genome-scale metabolic reconstruction presented here, which has been benchmarked against experimental data and correctly reproduces known phenotypes, provides an in silico platform with which to investigate the metabolism of this important human pathogen.

Published
2011

24. A community effort towards a knowledge-base and mathematical model of the human pathogen Salmonella Typhimurium LT2

Author

Thiele, Ines, Hyduke, Daniel R, Steeb, Benjamin, Fankam, Guy, Allen, Douglas K, Bazzani, Susanna, Charusanti, Pep, Chen, Feng-Chi, Fleming, Ronan MT, Hsiung, Chao A, De Keersmaecker, Sigrid CJ, Liao, Yu-Chieh, Marchal, Kathleen, Mo, Monica L, Özdemir, Emre, Raghunathan, Anu, Reed, Jennifer L, Shin, Sook-Il, Sigurbjörnsdóttir, Sara, Steinmann, Jonas, Sudarsan, Suresh, Swainston, Neil, Thijs, Inge M, Zengler, Karsten, Palsson, Bernhard O, Adkins, Joshua N, and Bumann, Dirk

Abstract

Abstract Background Metabolic reconstructions (MRs) are common denominators in systems biology and represent biochemical, genetic, and genomic (BiGG) knowledge-bases for target organisms by capturing currently available information in a consistent, structured manner. Salmonella enterica subspecies I serovar Typhimurium is a human pathogen, causes various diseases and its increasing antibiotic resistance poses a public health problem. Results Here, we describe a community-driven effort, in which more than 20 experts in S. Typhimurium biology and systems biology collaborated to reconcile and expand the S. Typhimurium BiGG knowledge-base. The consensus MR was obtained starting from two independently developed MRs for S. Typhimurium. Key results of this reconstruction jamboree include i) development and implementation of a community-based workflow for MR annotation and reconciliation; ii) incorporation of thermodynamic information; and iii) use of the consensus MR to identify potential multi-target drug therapy approaches. Conclusion Taken together, with the growing number of parallel MRs a structured, community-driven approach will be necessary to maximize quality while increasing adoption of MRs in experimental design and interpretation.

Published
2011

25. Comprehensive computational design of ordered peptide macrocycles

Author

Hosseinzadeh, Parisa, Bhardwaj, Gaurav, Mulligan, Vikram Khipple, Shortridge, Matthew D., Craven, Timothy W., Pardo-Avila, Fátima, Rettie, Stephen A., Kim, David E., Silva, Daniel-Adriano, Ibrahim, Yehia M., Webb, Ian K., Cort, John R., Adkins, Joshua N., Varani, Gabriele, and Baker, David

Published
2017

26. New insights into the natural history of bronchopulmonary dysplasia from proteomics and multiplexed immunohistochemistry

Author

Dylag, Andrew M., primary, Misra, Ravi S., additional, Bandyopadhyay, Gautam, additional, Poole, Cory, additional, Huyck, Heidie L., additional, Jehrio, Matthew G., additional, Haak, Jeannie, additional, Deutsch, Gail H., additional, Dvorak, Carly, additional, Olson, Heather M., additional, Paurus, Vanessa, additional, Katzman, Philip J., additional, Woo, Jongmin, additional, Purkerson, Jeffrey M., additional, Adkins, Joshua N., additional, Mariani, Thomas J., additional, Clair, Geremy C., additional, and Pryhuber, Gloria S., additional

Published
2023
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27. Global systems-level analysis of Hfq and SmpB deletion mutants in Salmonella: implications for virulence and global protein translation.

Author

Ansong, Charles, Yoon, Hyunjin, Porwollik, Steffen, Mottaz-Brewer, Heather, Petritis, Brianne O, Jaitly, Navdeep, Adkins, Joshua N, McClelland, Michael, Heffron, Fred, and Smith, Richard D

Subjects
Macrophages, Animals, Mice, Inbred BALB C, Mice, Salmonella typhimurium, Propylene Glycols, Bacterial Proteins, Host Factor 1 Protein, RNA-Binding Proteins, RNA, Bacterial, RNA, Messenger, Oligonucleotide Array Sequence Analysis, Gene Targeting, Proteomics, Virulence, Protein Biosynthesis, Gene Expression Regulation, Bacterial, Gene Deletion, Genes, Bacterial, Operon, Female, General Science & Technology
Abstract

Using sample-matched transcriptomics and proteomics measurements it is now possible to begin to understand the impact of post-transcriptional regulatory programs in Enterobacteria. In bacteria post-transcriptional regulation is mediated by relatively few identified RNA-binding protein factors including CsrA, Hfq and SmpB. A mutation in any one of these three genes, csrA, hfq, and smpB, in Salmonella is attenuated for mouse virulence and unable to survive in macrophages. CsrA has a clearly defined specificity based on binding to a specific mRNA sequence to inhibit translation. However, the proteins regulated by Hfq and SmpB are not as clearly defined. Previous work identified proteins regulated by hfq using purification of the RNA-protein complex with direct sequencing of the bound RNAs and found binding to a surprisingly large number of transcripts. In this report we have used global proteomics to directly identify proteins regulated by Hfq or SmpB by comparing protein abundance in the parent and isogenic hfq or smpB mutant. From these same samples we also prepared RNA for microarray analysis to determine if alteration of protein expression was mediated post-transcriptionally. Samples were analyzed from bacteria grown under four different conditions; two laboratory conditions and two that are thought to mimic the intracellular environment. We show that mutants of hfq and smpB directly or indirectly modulate at least 20% and 4% of all possible Salmonella proteins, respectively, with limited correlation between transcription and protein expression. These proteins represent a broad spectrum of Salmonella proteins required for many biological processes including host cell invasion, motility, central metabolism, LPS biosynthesis, two-component regulatory systems, and fatty acid metabolism. Our results represent one of the first global analyses of post-transcriptional regulons in any organism and suggest that regulation at the translational level is widespread and plays an important role in virulence regulation and environmental adaptation for Salmonella.

Published
2009

30. Studying Salmonellae and Yersiniae Host–Pathogen Interactions Using Integrated ‘Omics and Modeling

Author

Ansong, Charles, Deatherage, Brooke L., Hyduke, Daniel, Schmidt, Brian, McDermott, Jason E., Jones, Marcus B., Chauhan, Sadhana, Charusanti, Pep, Kim, Young-Mo, Nakayasu, Ernesto S., Li, Jie, Kidwai, Afshan, Niemann, George, Brown, Roslyn N., Metz, Thomas O., McAteer, Kathleen, Heffron, Fred, Peterson, Scott N., Motin, Vladimir, Palsson, Bernhard O., Smith, Richard D., Adkins, Joshua N., and Katze, Michael G., editor

Published
2013
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31. Sexual dimorphism and the multi-omic response to exercise training in rat subcutaneous white adipose tissue

Author

Many, Gina M., Sanford, James A., Sagendorf, Tyler J., Hou, Zhenxin, Nigro, Pasquale, Whytock, Katie, Amar, David, Caputo, Tiziana, Gay, Nicole R., Gaul, David A., Hirshman, Michael, Jimenez-Morales, David, Lindholm, Malene E., Muehlbauer, Michael J., Vamvini, Maria, Bergman, Bryan, Fern√°ndez, Facundo M., Goodyear, Laurie J., Ortlund, Eric A., Sparks, Lauren M., Xia, Ashley, Adkins, Joshua N., Bodine, Sue C., Newgard, Christopher B., and Schenk, Simon

Subjects
Article
Abstract

Subcutaneous white adipose tissue (scWAT) is a dynamic storage and secretory organ that regulates systemic homeostasis, yet the impact of endurance exercise training and sex on its molecular landscape has not been fully established. Utilizing an integrative multi-omics approach with data generated by the Molecular Transducers of Physical Activity Consortium (MoTrPAC), we identified profound sexual dimorphism in the dynamic response of rat scWAT to endurance exercise training. Despite similar cardiorespiratory improvements, only male rats reduced whole-body adiposity, scWAT adipocyte size, and total scWAT triglyceride abundance with training. Multi-omic analyses of adipose tissue integrated with phenotypic measures identified sex-specific training responses including enrichment of mTOR signaling in females, while males displayed enhanced mitochondrial ribosome biogenesis and oxidative metabolism. Overall, this study reinforces our understanding that sex impacts scWAT biology and provides a rich resource to interrogate responses of scWAT to endurance training.

Published
2023
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33. Sexual dimorphism and the multi-omic response to exercise training in rat subcutaneous white adipose tissue

Author

Many, Gina M, primary, Sanford, James A, additional, Sagendorf, Tyler J, additional, Hou, Zhenxin, additional, Nigro, Pasquale, additional, Whytock, Katie L, additional, Amar, David, additional, Caputo, Tiziana, additional, Gay, Nicole R, additional, Gaul, David A, additional, Hirshman, Michael F, additional, Jimenez-Morales, David, additional, Lindholm, Malene E, additional, Muehlbauer, Michael J, additional, Vamvini, Maria, additional, Bergman, Bryan C, additional, Fernandez, Facundo M, additional, Goodyear, Laurie J, additional, Ortlund, Eric A, additional, Sparks, Lauren M, additional, Xia, Ashley, additional, Adkins, Joshua N, additional, Bodine, Sue C, additional, Newgard, Christopher B, additional, Schenk, Simon, additional, and Study Group, The MoTrPAC, additional

Published
2023
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36. An optimized approach and inflation media for obtaining complimentary mass spectrometry-based omics data from human lung tissue

Author

Lukowski, Jessica K., primary, Olson, Heather, additional, Velickovic, Marija, additional, Wang, Juan, additional, Kyle, Jennifer E., additional, Kim, Young-Mo, additional, Williams, Sarah M., additional, Zhu, Ying, additional, Huyck, Heidi L., additional, McGraw, Matthew D., additional, Poole, Cory, additional, Rogers, Lisa, additional, Misra, Ravi, additional, Alexandrov, Theodore, additional, Ansong, Charles, additional, Pryhuber, Gloria S., additional, Clair, Geremy, additional, Adkins, Joshua N., additional, Carson, James P., additional, and Anderton, Christopher R., additional

Published
2022
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42. Guided construction of single cell reference for human and mouse lung

Author

Guo, Minzhe, primary, Morley, Michael P., additional, Wu, Yixin, additional, Du, Yina, additional, Zhao, Shuyang, additional, Wagner, Andrew, additional, Kouril, Michal, additional, Jin, Kang, additional, Gaddis, Nathan, additional, Kitzmiller, Joseph A., additional, Stewart, Kathleen, additional, Basil, Maria C., additional, Lin, Susan M., additional, Ying, Yun, additional, Babu, Apoorva, additional, Wikenheiser-Brokamp, Kathryn A., additional, Mun, Kyu Shik, additional, Naren, Anjaparavanda P., additional, Lin, Sara, additional, Clair, Geremy, additional, Adkins, Joshua N., additional, Pryhuber, Gloria S., additional, Misra, Ravi S., additional, Aronow, Bruce J., additional, Tickle, Timothy L., additional, Salomonis, Nathan, additional, Sun, Xin, additional, Morrisey, Edward E., additional, Whitsett, Jeffrey A., additional, and Xu, Yan, additional

Published
2022
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44. Proteomic Analysis of Human Lung Development

Author

Clair, Geremy, primary, Bramer, Lisa M., additional, Misra, Ravi, additional, McGraw, Matthew D., additional, Bhattacharya, Soumyaroop, additional, Kitzmiller, Joseph A., additional, Feng, Song, additional, Danna, Vincent G., additional, Bandyopadhyay, Gautam, additional, Bhotika, Harsh, additional, Huyck, Heidie L., additional, Deutsch, Gail H., additional, Mariani, Thomas J., additional, Carson, James P., additional, Whitsett, Jeffrey A., additional, Pryhuber, Gloria S., additional, Adkins, Joshua N., additional, and Ansong, Charles, additional

Published
2022
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