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1. Multi-level analysis of the gut-brain axis shows autism spectrum disorder-associated molecular and microbial profiles.

Author

Morton, James T, Jin, Dong-Min, Mills, Robert H, Shao, Yan, Rahman, Gibraan, McDonald, Daniel, Zhu, Qiyun, Balaban, Metin, Jiang, Yueyu, Cantrell, Kalen, Gonzalez, Antonio, Carmel, Julie, Frankiensztajn, Linoy Mia, Martin-Brevet, Sandra, Berding, Kirsten, Needham, Brittany D, Zurita, María Fernanda, David, Maude, Averina, Olga V, Kovtun, Alexey S, Noto, Antonio, Mussap, Michele, Wang, Mingbang, Frank, Daniel N, Li, Ellen, Zhou, Wenhao, Fanos, Vassilios, Danilenko, Valery N, Wall, Dennis P, Cárdenas, Paúl, Baldeón, Manuel E, Jacquemont, Sébastien, Koren, Omry, Elliott, Evan, Xavier, Ramnik J, Mazmanian, Sarkis K, Knight, Rob, Gilbert, Jack A, Donovan, Sharon M, Lawley, Trevor D, Carpenter, Bob, Bonneau, Richard, and Taroncher-Oldenburg, Gaspar

Subjects
Humans, Cytokines, Bayes Theorem, Cross-Sectional Studies, Reproducibility of Results, Autism Spectrum Disorder, Gastrointestinal Microbiome, Brain-Gut Axis, Mental Health, Behavioral and Social Science, Brain Disorders, Pediatric, Intellectual and Developmental Disabilities (IDD), Genetics, Pediatric Research Initiative, Neurosciences, Autism, 2.3 Psychological, social and economic factors, 2.1 Biological and endogenous factors, Aetiology, Mental health, Psychology, Cognitive Sciences, Neurology & Neurosurgery
Abstract

Autism spectrum disorder (ASD) is a neurodevelopmental disorder characterized by heterogeneous cognitive, behavioral and communication impairments. Disruption of the gut-brain axis (GBA) has been implicated in ASD although with limited reproducibility across studies. In this study, we developed a Bayesian differential ranking algorithm to identify ASD-associated molecular and taxa profiles across 10 cross-sectional microbiome datasets and 15 other datasets, including dietary patterns, metabolomics, cytokine profiles and human brain gene expression profiles. We found a functional architecture along the GBA that correlates with heterogeneity of ASD phenotypes, and it is characterized by ASD-associated amino acid, carbohydrate and lipid profiles predominantly encoded by microbial species in the genera Prevotella, Bifidobacterium, Desulfovibrio and Bacteroides and correlates with brain gene expression changes, restrictive dietary patterns and pro-inflammatory cytokine profiles. The functional architecture revealed in age-matched and sex-matched cohorts is not present in sibling-matched cohorts. We also show a strong association between temporal changes in microbiome composition and ASD phenotypes. In summary, we propose a framework to leverage multi-omic datasets from well-defined cohorts and investigate how the GBA influences ASD.

Published
2023

4. Whole-genome sequencing of African Americans implicates differential genetic architecture in inflammatory bowel disease.

Author

Somineni, Hari, Nagpal, Sini, Venkateswaran, Suresh, Cutler, David, Okou, David, Haritunians, Talin, Simpson, Claire, Begum, Ferdouse, Datta, Lisa, Quiros, Antonio, Seminerio, Jenifer, Mengesha, Emebet, Alexander, Jonathan, Baldassano, Robert, Dudley-Brown, Sharon, Cross, Raymond, Dassopoulos, Themistocles, Denson, Lee, Dhere, Tanvi, Iskandar, Heba, Dryden, Gerald, Hou, Jason, Hussain, Sunny, Hyams, Jeffrey, Isaacs, Kim, Kader, Howard, Kappelman, Michael, Katz, Jeffry, Kellermayer, Richard, Kuemmerle, John, Lazarev, Mark, Li, Ellen, Mannon, Peter, Moulton, Dedrick, Newberry, Rodney, Patel, Ashish, Pekow, Joel, Saeed, Shehzad, Valentine, John, Wang, Ming-Hsi, McCauley, Jacob, Abreu, Maria, Jester, Traci, Molle-Rios, Zarela, Palle, Sirish, Scherl, Ellen, Kwon, John, Rioux, John, Duerr, Richard, Silverberg, Mark, Zwick, Michael, Stevens, Christine, Daly, Mark, Cho, Judy, Gibson, Greg, McGovern, Dermot, Brant, Steven, and Kugathasan, Subra

Subjects
CALB2, PTGER4, differential genetic architecture, polygenic risk scores, rare variants, trans-ethnic comparative analysis, understudied populations, whole-genome sequencing of African Americans, Black or African American, Aged, Aged, 80 and over, Calbindin 2, Colitis, Ulcerative, Crohn Disease, Female, Gene Frequency, Genetic Predisposition to Disease, Genome-Wide Association Study, Humans, Inflammatory Bowel Diseases, Male, Multifactorial Inheritance, Polymorphism, Single Nucleotide, Receptors, Prostaglandin E, EP4 Subtype, White People, Whole Genome Sequencing
Abstract

Whether or not populations diverge with respect to the genetic contribution to risk of specific complex diseases is relevant to understanding the evolution of susceptibility and origins of health disparities. Here, we describe a large-scale whole-genome sequencing study of inflammatory bowel disease encompassing 1,774 affected individuals and 1,644 healthy control Americans with African ancestry (African Americans). Although no new loci for inflammatory bowel disease are discovered at genome-wide significance levels, we identify numerous instances of differential effect sizes in combination with divergent allele frequencies. For example, the major effect at PTGER4 fine maps to a single credible interval of 22 SNPs corresponding to one of four independent associations at the locus in European ancestry individuals but with an elevated odds ratio for Crohn disease in African Americans. A rare variant aggregate analysis implicates Ca2+-binding neuro-immunomodulator CALB2 in ulcerative colitis. Highly significant overall overlap of common variant risk for inflammatory bowel disease susceptibility between individuals with African and European ancestries was observed, with 41 of 241 previously known lead variants replicated and overall correlations in effect sizes of 0.68 for combined inflammatory bowel disease. Nevertheless, subtle differences influence the performance of polygenic risk scores, and we show that ancestry-appropriate weights significantly improve polygenic prediction in the highest percentiles of risk. The median amount of variance explained per locus remains the same in African and European cohorts, providing evidence for compensation of effect sizes as allele frequencies diverge, as expected under a highly polygenic model of disease.

Published
2021

6. Organoid Profiling Identifies Common Responders to Chemotherapy in Pancreatic Cancer.

Author

Tiriac, Hervé, Belleau, Pascal, Engle, Dannielle D, Plenker, Dennis, Deschênes, Astrid, Somerville, Tim DD, Froeling, Fieke EM, Burkhart, Richard A, Denroche, Robert E, Jang, Gun-Ho, Miyabayashi, Koji, Young, C Megan, Patel, Hardik, Ma, Michelle, LaComb, Joseph F, Palmaira, Randze Lerie D, Javed, Ammar A, Huynh, Jasmine C, Johnson, Molly, Arora, Kanika, Robine, Nicolas, Shah, Minita, Sanghvi, Rashesh, Goetz, Austin B, Lowder, Cinthya Y, Martello, Laura, Driehuis, Else, LeComte, Nicolas, Askan, Gokce, Iacobuzio-Donahue, Christine A, Clevers, Hans, Wood, Laura D, Hruban, Ralph H, Thompson, Elizabeth, Aguirre, Andrew J, Wolpin, Brian M, Sasson, Aaron, Kim, Joseph, Wu, Maoxin, Bucobo, Juan Carlos, Allen, Peter, Sejpal, Divyesh V, Nealon, William, Sullivan, James D, Winter, Jordan M, Gimotty, Phyllis A, Grem, Jean L, DiMaio, Dominick J, Buscaglia, Jonathan M, Grandgenett, Paul M, Brody, Jonathan R, Hollingsworth, Michael A, O'Kane, Grainne M, Notta, Faiyaz, Kim, Edward, Crawford, James M, Devoe, Craig, Ocean, Allyson, Wolfgang, Christopher L, Yu, Kenneth H, Li, Ellen, Vakoc, Christopher R, Hubert, Benjamin, Fischer, Sandra E, Wilson, Julie M, Moffitt, Richard, Knox, Jennifer, Krasnitz, Alexander, Gallinger, Steven, and Tuveson, David A

Subjects
Organoids, Tumor Cells, Cultured, Humans, Pancreatic Neoplasms, Antineoplastic Agents, Drug Screening Assays, Antitumor, Prospective Studies, Gene Expression Profiling, Sequence Analysis, RNA, Gene Expression Regulation, Neoplastic, Drug Resistance, Neoplasm, Gene Regulatory Networks, Molecular Targeted Therapy, Standard of Care, Precision Medicine, Genetics, Pancreatic Cancer, Rare Diseases, Digestive Diseases, Orphan Drug, Cancer, Detection, screening and diagnosis, Development of treatments and therapeutic interventions, 4.1 Discovery and preclinical testing of markers and technologies, 5.1 Pharmaceuticals, Good Health and Well Being, Oncology and Carcinogenesis
Abstract

Pancreatic cancer is the most lethal common solid malignancy. Systemic therapies are often ineffective, and predictive biomarkers to guide treatment are urgently needed. We generated a pancreatic cancer patient-derived organoid (PDO) library that recapitulates the mutational spectrum and transcriptional subtypes of primary pancreatic cancer. New driver oncogenes were nominated and transcriptomic analyses revealed unique clusters. PDOs exhibited heterogeneous responses to standard-of-care chemotherapeutics and investigational agents. In a case study manner, we found that PDO therapeutic profiles paralleled patient outcomes and that PDOs enabled longitudinal assessment of chemosensitivity and evaluation of synchronous metastases. We derived organoid-based gene expression signatures of chemosensitivity that predicted improved responses for many patients to chemotherapy in both the adjuvant and advanced disease settings. Finally, we nominated alternative treatment strategies for chemorefractory PDOs using targeted agent therapeutic profiling. We propose that combined molecular and therapeutic profiling of PDOs may predict clinical response and enable prospective therapeutic selection.Significance: New approaches to prioritize treatment strategies are urgently needed to improve survival and quality of life for patients with pancreatic cancer. Combined genomic, transcriptomic, and therapeutic profiling of PDOs can identify molecular and functional subtypes of pancreatic cancer, predict therapeutic responses, and facilitate precision medicine for patients with pancreatic cancer. Cancer Discov; 8(9); 1112-29. ©2018 AACR.See related commentary by Collisson, p. 1062This article is highlighted in the In This Issue feature, p. 1047.

Published
2018

9. Genome-Wide Association Study Identifies African-Specific Susceptibility Loci in African Americans With Inflammatory Bowel Disease.

Author

Brant, Steven, Okou, David, Simpson, Claire, Cutler, David, Haritunians, Talin, Bradfield, Jonathan, Chopra, Pankaj, Prince, Jarod, Begum, Ferdouse, Kumar, Archana, Huang, Chengrui, Venkateswaran, Suresh, Datta, Lisa, Wei, Zhi, Thomas, Kelly, Herrinton, Lisa, Klapproth, Jan-Micheal, Quiros, Antonio, Seminerio, Jenifer, Liu, Zhenqiu, Alexander, Jonathan, Baldassano, Robert, Dudley-Brown, Sharon, Cross, Raymond, Dassopoulos, Themistocles, Denson, Lee, Dhere, Tanvi, Dryden, Gerald, Hanson, John, Hou, Jason, Hussain, Sunny, Hyams, Jeffrey, Isaacs, Kim, Kader, Howard, Kappelman, Michael, Katz, Jeffry, Kellermayer, Richard, Kirschner, Barbara, Kuemmerle, John, Kwon, John, Lazarev, Mark, Li, Ellen, Mack, David, Mannon, Peter, Moulton, Dedrick, Newberry, Rodney, Osuntokun, Bankole, Patel, Ashish, Saeed, Shehzad, Targan, Stephan, Valentine, John, Wang, Ming-Hsi, Zonca, Martin, Rioux, John, Duerr, Richard, Silverberg, Mark, Cho, Judy, Hakonarson, Hakon, Zwick, Michael, McGovern, Dermot, and Kugathasan, Subra

Subjects
Genetic Analysis, Risk Factor, SNP, Trans-Ethnic, Adenylyl Cyclases, Black or African American, Case-Control Studies, Cell Adhesion Molecules, Neuronal, Colitis, Ulcerative, Crohn Disease, GPI-Linked Proteins, Genetic Predisposition to Disease, Genome-Wide Association Study, Genotyping Techniques, HLA-DQ alpha-Chains, HLA-DRB1 Chains, Humans, Interleukin-12 Subunit p40, KCNQ2 Potassium Channel, Polymorphism, Single Nucleotide, Receptors, CXCR6, Receptors, Chemokine, Receptors, Interleukin, Receptors, Prostaglandin E, EP4 Subtype, Receptors, Virus, Repressor Proteins, Sorting Nexins, Tenascin, Ubiquitin Thiolesterase, White People
Abstract

BACKGROUND & AIMS: The inflammatory bowel diseases (IBD) ulcerative colitis (UC) and Crohns disease (CD) cause significant morbidity and are increasing in prevalence among all populations, including African Americans. More than 200 susceptibility loci have been identified in populations of predominantly European ancestry, but few loci have been associated with IBD in other ethnicities. METHODS: We performed 2 high-density, genome-wide scans comprising 2345 cases of African Americans with IBD (1646 with CD, 583 with UC, and 116 inflammatory bowel disease unclassified) and 5002 individuals without IBD (controls, identified from the Health Retirement Study and Kaiser Permanente database). Single-nucleotide polymorphisms (SNPs) associated at P

Published
2017

12. A modular organization of the human intestinal mucosal microbiota and its association with inflammatory bowel disease.

Author

Tong, Maomeng, Li, Xiaoxiao, Wegener Parfrey, Laura, Roth, Bennett, Ippoliti, Andrew, Wei, Bo, Borneman, James, McGovern, Dermot PB, Frank, Daniel N, Li, Ellen, Horvath, Steve, Knight, Rob, and Braun, Jonathan

Subjects
Intestinal Mucosa, Humans, Inflammatory Bowel Diseases, RNA, Ribosomal, 16S, Cluster Analysis, Cohort Studies, Phenotype, Metagenome, Microbiota, General Science & Technology
Abstract

Abnormalities of the intestinal microbiota are implicated in the pathogenesis of Crohn's disease (CD) and ulcerative colitis (UC), two spectra of inflammatory bowel disease (IBD). However, the high complexity and low inter-individual overlap of intestinal microbial composition are formidable barriers to identifying microbial taxa representing this dysbiosis. These difficulties might be overcome by an ecologic analytic strategy to identify modules of interacting bacteria (rather than individual bacteria) as quantitative reproducible features of microbial composition in normal and IBD mucosa. We sequenced 16S ribosomal RNA genes from 179 endoscopic lavage samples from different intestinal regions in 64 subjects (32 controls, 16 CD and 16 UC patients in clinical remission). CD and UC patients showed a reduction in phylogenetic diversity and shifts in microbial composition, comparable to previous studies using conventional mucosal biopsies. Analysis of weighted co-occurrence network revealed 5 microbial modules. These modules were unprecedented, as they were detectable in all individuals, and their composition and abundance was recapitulated in an independent, biopsy-based mucosal dataset 2 modules were associated with healthy, CD, or UC disease states. Imputed metagenome analysis indicated that these modules displayed distinct metabolic functionality, specifically the enrichment of oxidative response and glycan metabolism pathways relevant to host-pathogen interaction in the disease-associated modules. The highly preserved microbial modules accurately classified IBD status of individual patients during disease quiescence, suggesting that microbial dysbiosis in IBD may be an underlying disorder independent of disease activity. Microbial modules thus provide an integrative view of microbial ecology relevant to IBD.

Published
2013

14. Table S3 from Organoid Profiling Identifies Common Responders to Chemotherapy in Pancreatic Cancer

Author

Tiriac, Hervé, primary, Belleau, Pascal, primary, Engle, Dannielle D., primary, Plenker, Dennis, primary, Deschênes, Astrid, primary, Somerville, Tim D. D., primary, Froeling, Fieke E. M., primary, Burkhart, Richard A., primary, Denroche, Robert E., primary, Jang, Gun-Ho, primary, Miyabayashi, Koji, primary, Young, C. Megan, primary, Patel, Hardik, primary, Ma, Michelle, primary, LaComb, Joseph F., primary, Palmaira, Randze Lerie D., primary, Javed, Ammar A., primary, Huynh, Jasmine C., primary, Johnson, Molly, primary, Arora, Kanika, primary, Robine, Nicolas, primary, Shah, Minita, primary, Sanghvi, Rashesh, primary, Goetz, Austin B., primary, Lowder, Cinthya Y., primary, Martello, Laura, primary, Driehuis, Else, primary, LeComte, Nicolas, primary, Askan, Gokce, primary, Iacobuzio-Donahue, Christine A., primary, Clevers, Hans, primary, Wood, Laura D., primary, Hruban, Ralph H., primary, Thompson, Elizabeth, primary, Aguirre, Andrew J., primary, Wolpin, Brian M., primary, Sasson, Aaron, primary, Kim, Joseph, primary, Wu, Maoxin, primary, Bucobo, Juan Carlos, primary, Allen, Peter, primary, Sejpal, Divyesh V., primary, Nealon, William, primary, Sullivan, James D., primary, Winter, Jordan M., primary, Gimotty, Phyllis A., primary, Grem, Jean L., primary, DiMaio, Dominick J., primary, Buscaglia, Jonathan M., primary, Grandgenett, Paul M., primary, Brody, Jonathan R., primary, Hollingsworth, Michael A., primary, O'Kane, Grainne M., primary, Notta, Faiyaz, primary, Kim, Edward, primary, Crawford, James M., primary, Devoe, Craig, primary, Ocean, Allyson, primary, Wolfgang, Christopher L., primary, Yu, Kenneth H., primary, Li, Ellen, primary, Vakoc, Christopher R., primary, Hubert, Benjamin, primary, Fischer, Sandra E., primary, Wilson, Julie M., primary, Moffitt, Richard, primary, Knox, Jennifer, primary, Krasnitz, Alexander, primary, Gallinger, Steven, primary, and Tuveson, David A., primary

Published
2023
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15. Data from Organoid Profiling Identifies Common Responders to Chemotherapy in Pancreatic Cancer

Author

Tiriac, Hervé, primary, Belleau, Pascal, primary, Engle, Dannielle D., primary, Plenker, Dennis, primary, Deschênes, Astrid, primary, Somerville, Tim D. D., primary, Froeling, Fieke E. M., primary, Burkhart, Richard A., primary, Denroche, Robert E., primary, Jang, Gun-Ho, primary, Miyabayashi, Koji, primary, Young, C. Megan, primary, Patel, Hardik, primary, Ma, Michelle, primary, LaComb, Joseph F., primary, Palmaira, Randze Lerie D., primary, Javed, Ammar A., primary, Huynh, Jasmine C., primary, Johnson, Molly, primary, Arora, Kanika, primary, Robine, Nicolas, primary, Shah, Minita, primary, Sanghvi, Rashesh, primary, Goetz, Austin B., primary, Lowder, Cinthya Y., primary, Martello, Laura, primary, Driehuis, Else, primary, LeComte, Nicolas, primary, Askan, Gokce, primary, Iacobuzio-Donahue, Christine A., primary, Clevers, Hans, primary, Wood, Laura D., primary, Hruban, Ralph H., primary, Thompson, Elizabeth, primary, Aguirre, Andrew J., primary, Wolpin, Brian M., primary, Sasson, Aaron, primary, Kim, Joseph, primary, Wu, Maoxin, primary, Bucobo, Juan Carlos, primary, Allen, Peter, primary, Sejpal, Divyesh V., primary, Nealon, William, primary, Sullivan, James D., primary, Winter, Jordan M., primary, Gimotty, Phyllis A., primary, Grem, Jean L., primary, DiMaio, Dominick J., primary, Buscaglia, Jonathan M., primary, Grandgenett, Paul M., primary, Brody, Jonathan R., primary, Hollingsworth, Michael A., primary, O'Kane, Grainne M., primary, Notta, Faiyaz, primary, Kim, Edward, primary, Crawford, James M., primary, Devoe, Craig, primary, Ocean, Allyson, primary, Wolfgang, Christopher L., primary, Yu, Kenneth H., primary, Li, Ellen, primary, Vakoc, Christopher R., primary, Hubert, Benjamin, primary, Fischer, Sandra E., primary, Wilson, Julie M., primary, Moffitt, Richard, primary, Knox, Jennifer, primary, Krasnitz, Alexander, primary, Gallinger, Steven, primary, and Tuveson, David A., primary

Published
2023
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16. Supplemental Figures from Organoid Profiling Identifies Common Responders to Chemotherapy in Pancreatic Cancer

Author

Tiriac, Hervé, primary, Belleau, Pascal, primary, Engle, Dannielle D., primary, Plenker, Dennis, primary, Deschênes, Astrid, primary, Somerville, Tim D. D., primary, Froeling, Fieke E. M., primary, Burkhart, Richard A., primary, Denroche, Robert E., primary, Jang, Gun-Ho, primary, Miyabayashi, Koji, primary, Young, C. Megan, primary, Patel, Hardik, primary, Ma, Michelle, primary, LaComb, Joseph F., primary, Palmaira, Randze Lerie D., primary, Javed, Ammar A., primary, Huynh, Jasmine C., primary, Johnson, Molly, primary, Arora, Kanika, primary, Robine, Nicolas, primary, Shah, Minita, primary, Sanghvi, Rashesh, primary, Goetz, Austin B., primary, Lowder, Cinthya Y., primary, Martello, Laura, primary, Driehuis, Else, primary, LeComte, Nicolas, primary, Askan, Gokce, primary, Iacobuzio-Donahue, Christine A., primary, Clevers, Hans, primary, Wood, Laura D., primary, Hruban, Ralph H., primary, Thompson, Elizabeth, primary, Aguirre, Andrew J., primary, Wolpin, Brian M., primary, Sasson, Aaron, primary, Kim, Joseph, primary, Wu, Maoxin, primary, Bucobo, Juan Carlos, primary, Allen, Peter, primary, Sejpal, Divyesh V., primary, Nealon, William, primary, Sullivan, James D., primary, Winter, Jordan M., primary, Gimotty, Phyllis A., primary, Grem, Jean L., primary, DiMaio, Dominick J., primary, Buscaglia, Jonathan M., primary, Grandgenett, Paul M., primary, Brody, Jonathan R., primary, Hollingsworth, Michael A., primary, O'Kane, Grainne M., primary, Notta, Faiyaz, primary, Kim, Edward, primary, Crawford, James M., primary, Devoe, Craig, primary, Ocean, Allyson, primary, Wolfgang, Christopher L., primary, Yu, Kenneth H., primary, Li, Ellen, primary, Vakoc, Christopher R., primary, Hubert, Benjamin, primary, Fischer, Sandra E., primary, Wilson, Julie M., primary, Moffitt, Richard, primary, Knox, Jennifer, primary, Krasnitz, Alexander, primary, Gallinger, Steven, primary, and Tuveson, David A., primary

Published
2023
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17. Supplemental Table Legends from Organoid Profiling Identifies Common Responders to Chemotherapy in Pancreatic Cancer

Author

Tiriac, Hervé, primary, Belleau, Pascal, primary, Engle, Dannielle D., primary, Plenker, Dennis, primary, Deschênes, Astrid, primary, Somerville, Tim D. D., primary, Froeling, Fieke E. M., primary, Burkhart, Richard A., primary, Denroche, Robert E., primary, Jang, Gun-Ho, primary, Miyabayashi, Koji, primary, Young, C. Megan, primary, Patel, Hardik, primary, Ma, Michelle, primary, LaComb, Joseph F., primary, Palmaira, Randze Lerie D., primary, Javed, Ammar A., primary, Huynh, Jasmine C., primary, Johnson, Molly, primary, Arora, Kanika, primary, Robine, Nicolas, primary, Shah, Minita, primary, Sanghvi, Rashesh, primary, Goetz, Austin B., primary, Lowder, Cinthya Y., primary, Martello, Laura, primary, Driehuis, Else, primary, LeComte, Nicolas, primary, Askan, Gokce, primary, Iacobuzio-Donahue, Christine A., primary, Clevers, Hans, primary, Wood, Laura D., primary, Hruban, Ralph H., primary, Thompson, Elizabeth, primary, Aguirre, Andrew J., primary, Wolpin, Brian M., primary, Sasson, Aaron, primary, Kim, Joseph, primary, Wu, Maoxin, primary, Bucobo, Juan Carlos, primary, Allen, Peter, primary, Sejpal, Divyesh V., primary, Nealon, William, primary, Sullivan, James D., primary, Winter, Jordan M., primary, Gimotty, Phyllis A., primary, Grem, Jean L., primary, DiMaio, Dominick J., primary, Buscaglia, Jonathan M., primary, Grandgenett, Paul M., primary, Brody, Jonathan R., primary, Hollingsworth, Michael A., primary, O'Kane, Grainne M., primary, Notta, Faiyaz, primary, Kim, Edward, primary, Crawford, James M., primary, Devoe, Craig, primary, Ocean, Allyson, primary, Wolfgang, Christopher L., primary, Yu, Kenneth H., primary, Li, Ellen, primary, Vakoc, Christopher R., primary, Hubert, Benjamin, primary, Fischer, Sandra E., primary, Wilson, Julie M., primary, Moffitt, Richard, primary, Knox, Jennifer, primary, Krasnitz, Alexander, primary, Gallinger, Steven, primary, and Tuveson, David A., primary

Published
2023
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18. Supplemental Figure Legends from Organoid Profiling Identifies Common Responders to Chemotherapy in Pancreatic Cancer

Author

Tiriac, Hervé, primary, Belleau, Pascal, primary, Engle, Dannielle D., primary, Plenker, Dennis, primary, Deschênes, Astrid, primary, Somerville, Tim D. D., primary, Froeling, Fieke E. M., primary, Burkhart, Richard A., primary, Denroche, Robert E., primary, Jang, Gun-Ho, primary, Miyabayashi, Koji, primary, Young, C. Megan, primary, Patel, Hardik, primary, Ma, Michelle, primary, LaComb, Joseph F., primary, Palmaira, Randze Lerie D., primary, Javed, Ammar A., primary, Huynh, Jasmine C., primary, Johnson, Molly, primary, Arora, Kanika, primary, Robine, Nicolas, primary, Shah, Minita, primary, Sanghvi, Rashesh, primary, Goetz, Austin B., primary, Lowder, Cinthya Y., primary, Martello, Laura, primary, Driehuis, Else, primary, LeComte, Nicolas, primary, Askan, Gokce, primary, Iacobuzio-Donahue, Christine A., primary, Clevers, Hans, primary, Wood, Laura D., primary, Hruban, Ralph H., primary, Thompson, Elizabeth, primary, Aguirre, Andrew J., primary, Wolpin, Brian M., primary, Sasson, Aaron, primary, Kim, Joseph, primary, Wu, Maoxin, primary, Bucobo, Juan Carlos, primary, Allen, Peter, primary, Sejpal, Divyesh V., primary, Nealon, William, primary, Sullivan, James D., primary, Winter, Jordan M., primary, Gimotty, Phyllis A., primary, Grem, Jean L., primary, DiMaio, Dominick J., primary, Buscaglia, Jonathan M., primary, Grandgenett, Paul M., primary, Brody, Jonathan R., primary, Hollingsworth, Michael A., primary, O'Kane, Grainne M., primary, Notta, Faiyaz, primary, Kim, Edward, primary, Crawford, James M., primary, Devoe, Craig, primary, Ocean, Allyson, primary, Wolfgang, Christopher L., primary, Yu, Kenneth H., primary, Li, Ellen, primary, Vakoc, Christopher R., primary, Hubert, Benjamin, primary, Fischer, Sandra E., primary, Wilson, Julie M., primary, Moffitt, Richard, primary, Knox, Jennifer, primary, Krasnitz, Alexander, primary, Gallinger, Steven, primary, and Tuveson, David A., primary

Published
2023
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19. Risk Factors for Surgical Recurrence after Ileocolic Resection of Crohn’s Disease

Author

Unkart, Jonathan, Anderson, Lauren, Li, Ellen, Miller, Candace, Yan, Yan, Charles Gu, C., Chen, Jiajing, Stone, Christian, Hunt, Steven, and Dietz, David

Abstract

Abstract: Purpose: We evaluated the effect of potential clinical factors on surgical recurrence of ileal Crohn’s disease after initial ileocolic resection. Methods: One hundred seventy-six patients with ileal Crohn’s disease who underwent an ileocolic resection with anastomosis were identified from our database. The outcome of interest was time from first to second ileocolic resection. Survival analysis was used to assess the significance of the Montreal phenotype classification, smoking habit, a family history of inflammatory bowel disease and other clinical variables. Results: In our final Cox model, a family history of inflammatory bowel disease (hazard ratio 2.24, 95 percent confidence interval 1.16–4.30, P = 0.016), smoking at time of initial ileocolic resection (hazard ratio 2.08, 95 percent confidence interval 1.11–3.91, P = 0.023) was associated with an increased risk of a second ileocolic resection while postoperative prescription of immunomodulators (hazard ratio 0.40, 95 percent confidence interval 0.18–0.88, P = 0.022) was associated with a decreased risk of a second ileocolic resection. Conclusions: Both a family history of inflammatory bowel disease and smoking at the time of the initial ileocolic resection are associated with an increased risk of a second ileocolic resection. Postoperative prescription of immunomodulators is associated with a reduced risk of surgical recurrence. This study supports the concept that both genetic and environmental factors influence the risk of surgical recurrence of ileal Crohn’s disease.

Published
2024
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21. Multi-level analysis of the gut–brain axis shows autism spectrum disorder-associated molecular and microbial profiles

Author

Morton, James T., Jin, Dong-Min, Mills, Robert H., Shao, Yan, Rahman, Gibraan, McDonald, Daniel, Zhu, Qiyun, Balaban, Metin, Jiang, Yueyu, Cantrell, Kalen, Gonzalez, Antonio, Carmel, Julie, Frankiensztajn, Linoy Mia, Martin-Brevet, Sandra, Berding, Kirsten, Needham, Brittany D., Zurita, María Fernanda, David, Maude, Averina, Olga V., Kovtun, Alexey S., Noto, Antonio, Mussap, Michele, Wang, Mingbang, Frank, Daniel N., Li, Ellen, Zhou, Wenhao, Fanos, Vassilios, Danilenko, Valery N., Wall, Dennis P., Cárdenas, Paúl, Baldeón, Manuel E., Jacquemont, Sébastien, Koren, Omry, Elliott, Evan, Xavier, Ramnik J., Mazmanian, Sarkis K., Knight, Rob, Gilbert, Jack A., Donovan, Sharon M., Lawley, Trevor D., Carpenter, Bob, Bonneau, Richard, and Taroncher-Oldenburg, Gaspar

Abstract

Autism spectrum disorder (ASD) is a neurodevelopmental disorder characterized by heterogeneous cognitive, behavioral and communication impairments. Disruption of the gut–brain axis (GBA) has been implicated in ASD although with limited reproducibility across studies. In this study, we developed a Bayesian differential ranking algorithm to identify ASD-associated molecular and taxa profiles across 10 cross-sectional microbiome datasets and 15 other datasets, including dietary patterns, metabolomics, cytokine profiles and human brain gene expression profiles. We found a functional architecture along the GBA that correlates with heterogeneity of ASD phenotypes, and it is characterized by ASD-associated amino acid, carbohydrate and lipid profiles predominantly encoded by microbial species in the genera Prevotella, Bifidobacterium, Desulfovibrio and Bacteroides and correlates with brain gene expression changes, restrictive dietary patterns and pro-inflammatory cytokine profiles. The functional architecture revealed in age-matched and sex-matched cohorts is not present in sibling-matched cohorts. We also show a strong association between temporal changes in microbiome composition and ASD phenotypes. In summary, we propose a framework to leverage multi-omic datasets from well-defined cohorts and investigate how the GBA influences ASD.

Published
2023

23. Supplemental Methods and References from miR-181a-5p Inhibits Cancer Cell Migration and Angiogenesis via Downregulation of Matrix Metalloproteinase-14

Author

Li, Yiyi, primary, Kuscu, Cem, primary, Banach, Anna, primary, Zhang, Qian, primary, Pulkoski-Gross, Ashleigh, primary, Kim, Deborah, primary, Liu, Jingxuan, primary, Roth, Eric, primary, Li, Ellen, primary, Shroyer, Kenneth R., primary, Denoya, Paula I., primary, Zhu, Xiaoxia, primary, Chen, Longhua, primary, and Cao, Jian, primary

Published
2023
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24. Data from miR-181a-5p Inhibits Cancer Cell Migration and Angiogenesis via Downregulation of Matrix Metalloproteinase-14

Author

Li, Yiyi, primary, Kuscu, Cem, primary, Banach, Anna, primary, Zhang, Qian, primary, Pulkoski-Gross, Ashleigh, primary, Kim, Deborah, primary, Liu, Jingxuan, primary, Roth, Eric, primary, Li, Ellen, primary, Shroyer, Kenneth R., primary, Denoya, Paula I., primary, Zhu, Xiaoxia, primary, Chen, Longhua, primary, and Cao, Jian, primary

Published
2023
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33. Orkambi® and amplifier co‐therapy improves function from a rare CFTR mutation in gene‐edited cells and patient tissue

Author

Molinski, Steven V, Ahmadi, Saumel, Ip, Wan, Ouyang, Hong, Villella, Adriana, Miller, John P, Lee, Po‐Shun, Kulleperuma, Kethika, Du, Kai, Di Paola, Michelle, Eckford, Paul DW, Laselva, Onofrio, Huan, Ling Jun, Wellhauser, Leigh, Li, Ellen, Ray, Peter N, Pomès, Régis, Moraes, Theo J, Gonska, Tanja, Ratjen, Felix, and Bear, Christine E

Published
2017
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36. Multi-omic analysis along the gut-brain axis points to a functional architecture of autism

Author

Morton, James T, primary, Jin, Dong-min, additional, Mills, Robert, additional, Shao, Yan, additional, Rahman, Gibraan, additional, Harold-Berding, Kirsten, additional, Needham, Brittany D, additional, Zurita, Maria Fernanda, additional, David, Maude, additional, Averina, Olga, additional, Kovtun, Alexey, additional, Noto, Antonio, additional, Mussap, Michele, additional, Wang, Mingbang, additional, Frank, Daniel, additional, Li, Ellen, additional, Zhou, Wenhao, additional, Fanos, Vassilios, additional, Danilenko, Valery, additional, Wall, Dennis P., additional, Cardenas, Paul A, additional, Baldeon, Manuel, additional, xavier, ramnik j, additional, Mazmanian, Sarkis, additional, Knight, Rob, additional, Gilbert, Jack, additional, Donovan, Sharon, additional, Lawley, Trevor, additional, Carpenter, Bob, additional, Bonneau, Richard, additional, and Taroncher-Oldenburg, Gaspar, additional

Published
2022
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37. Integrated metagenomic and bile acid metabolomic analysis of human fecal microbiota transplantation for recurrent Clostridioides difficile and/or inflammatory bowel diseases

Author

Ramos, Ruben Jesus Faustino, primary, Zhu, Chencan, additional, Joseph, Dimitri F, additional, Thaker, Shubh D, additional, LaComb, Joseph F, additional, Markarian, Katherine, additional, Littmann, Eric R., additional, Lee, Hannah J, additional, Petrov, Jessica C, additional, Monzur, Farah, additional, Morganstern, Bradley M, additional, Bucobo, Juan Carlos, additional, Buscaglia, Jonathan M, additional, Chawla, Anupama, additional, Small-Harary, Lesley, additional, Gathungu, Grace, additional, Morganstern, Jeffrey A, additional, Yang, Jie, additional, Li, Jinyu, additional, Robertson, Charles E, additional, Pamer, Eric G., additional, Frank, Daniel N, additional, Cross, Justin R, additional, and Li, Ellen, additional

Published
2022
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38. Metagenomic and Bile Acid Metabolomic Analysis of Fecal Microbiota Transplantation for Recurrent Clostridiodes Difficile and/or Inflammatory Bowel Diseases

Author

Ramos, Ruben, primary, Zhu, Chencan, additional, Joseph, Dimitri, additional, Thaker, Shubh, additional, LaComb, Joseph, additional, Markarian, Katherine, additional, Lee, Hannah, additional, Petrov, Jessica, additional, Monzur, Farah, additional, Buscaglia, Jonathan, additional, Chawla, Anupama, additional, Small-Harary, Leslie, additional, Gathungu, Grace, additional, Morganstern, Jeffrey, additional, Yang, Jie, additional, Li, Jinyu, additional, Pamer, Eric, additional, Robertson, Charles, additional, Frank, Daniel, additional, Cross, Justin, additional, and Li, Ellen, additional

Published
2022
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48. Impact of type 2 diabetes on adenoma detection in screening colonoscopies performed in disparate populations

Author

Joseph, Dimitri F, primary, Li, Ellen, additional, Stanley III, Samuel L, additional, Zhu, Yi-Cong, additional, Li, Xiao-Ning, additional, Yang, Jie, additional, Ottaviano, Lorenzo F, additional, Bucobo, Juan Carlos, additional, Buscaglia, Jonathan M, additional, Miller, Joshua D, additional, Veluvolu, Rajesh, additional, Follen, Michele, additional, and Grossman, Evan B, additional

Published
2021
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49. Impact of preoperative antibiotics and other variables on integrated microbiome-host transcriptomic data generated from colorectal cancer resections

Author

Malik, Sarah A, primary, Zhu, Chencan, additional, Li, Jinyu, additional, LaComb, Joseph F, additional, Denoya, Paula I, additional, Kravets, Igor, additional, Miller, Joshua D, additional, Yang, Jie, additional, Kramer, Melissa, additional, McCombie, W Richard, additional, Robertson, Charles E, additional, Frank, Daniel N, additional, and Li, Ellen, additional

Published
2021
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