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1. Democratizing knowledge representation with BioCypher

Author

Lobentanzer, Sebastian, Aloy, Patrick, Baumbach, Jan, Bohar, Balazs, Carey, Vincent J., Charoentong, Pornpimol, Danhauser, Katharina, Doğan, Tunca, Dreo, Johann, Dunham, Ian, Farr, Elias, Fernandez-Torras, Adrià, Gyori, Benjamin M., Hartung, Michael, Hoyt, Charles Tapley, Klein, Christoph, Korcsmaros, Tamas, Maier, Andreas, Mann, Matthias, Ochoa, David, Pareja-Lorente, Elena, Popp, Ferdinand, Preusse, Martin, Probul, Niklas, Schwikowski, Benno, Sen, Bünyamin, Strauss, Maximilian T., Turei, Denes, Ulusoy, Erva, Waltemath, Dagmar, Wodke, Judith A. H., and Saez-Rodriguez, Julio

Published
2023
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3. Alpha-1 Antitrypsin MZ Heterozygosity Is an Endotype of Chronic Obstructive Pulmonary Disease.

Author

Ghosh, Auyon J, Hobbs, Brian D, Moll, Matthew, Saferali, Aabida, Boueiz, Adel, Yun, Jeong H, Sciurba, Frank, Barwick, Lucas, Limper, Andrew H, Flaherty, Kevin, Criner, Gerard, Brown, Kevin K, Wise, Robert, Martinez, Fernando J, Lomas, David, Castaldi, Peter J, Carey, Vincent J, DeMeo, Dawn L, Cho, Michael H, Silverman, Edwin K, Hersh, Craig P, Crapo, James D, Make, Barry J, Regan, Elizabeth A, Beaty, Terri H, El-Boueiz, Adel, Foreman, Marilyn G, Hayden, Lystra P, Hetmanski, Jacqueline, Hokanson, John E, Kim, Wonji, Laird, Nan, Lange, Christoph, Lutz, Sharon M, McDonald, Merry-Lynn, Prokopenko, Dmitry, Morrow, Jarrett, Qiao, Dandi, Sakornsakolpat, Phuwanat, Wan, Emily S, Centeno, Juan Pablo, Charbonnier, Jean-Paul, Coxson, Harvey O, Galban, Craig J, Han, MeiLan K, Hoffman, Eric A, Humphries, Stephen, Jacobson, Francine L, Judy, Philip F, Kazerooni, Ella A, Kluiber, Alex, Lynch, David A, Nardelli, Pietro, Newell, John D, Notary, Aleena, Oh, Andrea, Ross, James C, Estepar, Raul San Jose, Schroeder, Joyce, Sieren, Jered, Stoel, Berend C, Tschirren, Juerg, Van Beek, Edwin, van Ginneken, Bram, van Rikxoort, Eva, Sanchez-Ferrero, Gonzalo Vegas, Veitel, Lucas, Washko, George R, Wilson, Carla G, Jensen, Robert, Everett, Douglas, Crooks, Jim, Pratte, Katherine, Strand, Matt, Austin, Erin, Kinney, Gregory, Young, Kendra A, Bhatt, Surya P, Bon, Jessica, Diaz, Alejandro A, Make, Barry, Murray, Susan, Regan, Elizabeth, Soler, Xavier, Bowler, Russell P, Kechris, Katerina, Banaei-Kashani, Farnoush, Curtis, Jeffrey L, Pernicano, Perry G, and Hanania, Nicola

Subjects
Biomedical and Clinical Sciences, Cardiovascular Medicine and Haematology, Clinical Sciences, Chronic Obstructive Pulmonary Disease, Lung, Emphysema, Clinical Research, Aetiology, 2.1 Biological and endogenous factors, Respiratory, Adult, Aged, Aged, 80 and over, Case-Control Studies, Female, Genetic Markers, Genotype, Heterozygote, Humans, Longitudinal Studies, Male, Middle Aged, Phenotype, Pulmonary Disease, Chronic Obstructive, Respiratory Function Tests, Survival Analysis, Whole Genome Sequencing, alpha 1-Antitrypsin, COPDGene Investigators, RNA sequencing, alpha-1 antitrypsin, chronic obstructive pulmonary disease, meta-analysis, Medical and Health Sciences, Respiratory System, Cardiovascular medicine and haematology, Clinical sciences
Abstract

Rationale: Multiple studies have demonstrated an increased risk of chronic obstructive pulmonary disease (COPD) in heterozygous carriers of the AAT (alpha-1 antitrypsin) Z allele. However, it is not known if MZ subjects with COPD are phenotypically different from noncarriers (MM genotype) with COPD. Objectives: To assess if MZ subjects with COPD have different clinical features compared with MM subjects with COPD. Methods: Genotypes of SERPINA1 were ascertained by using whole-genome sequencing data in three independent studies. We compared outcomes between MM subjects with COPD and MZ subjects with COPD in each study and combined the results in a meta-analysis. We performed longitudinal and survival analyses to compare outcomes in MM and MZ subjects with COPD over time. Measurements and Main Results: We included 290 MZ subjects with COPD and 6,184 MM subjects with COPD across the three studies. MZ subjects had a lower FEV1% predicted and greater quantitative emphysema on chest computed tomography scans compared with MM subjects. In a meta-analysis, the FEV1 was 3.9% lower (95% confidence interval [CI], -6.55% to -1.26%) and emphysema (the percentage of lung attenuation areas

Published
2022

9. Partial correlation network analysis identifies coordinated gene expression within a regional cluster of COPD genome-wide association signals.

Author

Gentili, Michele, Glass, Kimberly, Maiorino, Enrico, Hobbs, Brian D., Xu, Zhonghui, Castaldi, Peter J., Cho, Michael H., Hersh, Craig P., Qiao, Dandi, Morrow, Jarrett D., Carey, Vincent J., Platig, John, and Silverman, Edwin K.

Subjects
CHRONIC obstructive pulmonary disease, GENE expression, GENOME-wide association studies, REGULATOR genes, GENETIC variation
Abstract

Chronic obstructive pulmonary disease (COPD) is a complex disease influenced by well-established environmental exposures (most notably, cigarette smoking) and incompletely defined genetic factors. The chromosome 4q region harbors multiple genetic risk loci for COPD, including signals near HHIP, FAM13A, GSTCD, TET2, and BTC. Leveraging RNA-Seq data from lung tissue in COPD cases and controls, we estimated the co-expression network for genes in the 4q region bounded by HHIP and BTC (~70MB), through partial correlations informed by protein-protein interactions. We identified several co-expressed gene pairs based on partial correlations, including NPNT-HHIP, BTC-NPNT and FAM13A-TET2, which were replicated in independent lung tissue cohorts. Upon clustering the co-expression network, we observed that four genes previously associated to COPD: BTC, HHIP, NPNT and PPM1K appeared in the same network community. Finally, we discovered a sub-network of genes differentially co-expressed between COPD vs controls (including FAM13A, PPA2, PPM1K and TET2). Many of these genes were previously implicated in cell-based knock-out experiments, including the knocking out of SPP1 which belongs to the same genomic region and could be a potential local key regulatory gene. These analyses identify chromosome 4q as a region enriched for COPD genetic susceptibility and differential co-expression. Author summary: Complex diseases, such as chronic obstructive pulmonary disease (COPD), are characterized by multifactorial causes, including multiple genetic variants and a variety of molecular functions. A 70 megabase genomic region on chromosome 4 harbors some of the strongest genetic associations to COPD based on genome-wide association studies (GWAS). In this work we study the co-expression patterns of genes located in this genomic region. We developed a new approach to compute partial correlations between pairs of expressed genes, using prior information regarding the mediating genes from protein-protein interaction networks. We identified potential biological connections between several of the COPD-related GWAS genes in this region, including BTC, NPNT, PPM1K and HHIP, suggesting possible functional co-regulation. Furthermore, by comparing COPD cases and control subjects, we found multiple network edges whose co-expression changed between health and disease, particularly the edge between CXCL10 and CXCL11. Some of these genes were previously implicated in cell-based knock-out experiments, suggesting a common regulator, namely SPP1. These analyses provide insight into regional gene regulation of GWAS genes that may be related to COPD pathogenesis. [ABSTRACT FROM AUTHOR]

Published
2024
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10. Inverting the model of genomics data sharing with the NHGRI Genomic Data Science Analysis, Visualization, and Informatics Lab-space

Author

Baumann, Alexander, Rula, Andrew, Kovalsy, Anton, Bernard, Clare, Caetano-Anollés, Derek, Van der Auwera, Geraldine A., Canas, Justin, Yuksel, Kaan, Herman, Kate, Taylor, M. Morgan, Simeon, Marianie, Baumann, Michael, Wang, Qi, Title, Robert, Munshi, Ruchi, Chaluvadi, Sushma, Reeves, Valerie, Disman, William, Thomas, Salin, Hajian, Allie, Kiernan, Elizabeth, Gupta, Namrata, Vosburg, Trish, Geistlinger, Ludwig, Ramos, Marcel, Oh, Sehyun, Rogers, Dave, McDade, Frances, Hastie, Mim, Turaga, Nitesh, Ostrovsky, Alexander, Mahmoud, Alexandru, Baker, Dannon, Clements, Dave, Cox, Katherine E.L., Suderman, Keith, Kucher, Nataliya, Golitsynskiy, Sergey, Zarate, Samantha, Wheelan, Sarah J., Kammers, Kai, Stevens, Ana, Hutter, Carolyn, Wellington, Christopher, Ghanaim, Elena M., Wiley, Ken L., Jr., Sen, Shurjo K., Di Francesco, Valentina, s Yuen, Deni, Walsh, Brian, Sargent, Luke, Jalili, Vahid, Chilton, John, Shepherd, Lori, Stubbs, B.J., O’Farrell, Ash, Vizzier, Benton A., Jr., Overbeck, Charles, Reid, Charles, Steinberg, David Charles, Sheets, Elizabeth A., Lucas, Julian, Blauvelt, Lon, Cabansay, Louise, Warren, Noah, Hannafious, Brian, Harris, Tim, Reddy, Radhika, Torstenson, Eric, Banasiewicz, M. Katie, Abel, Haley J., Walker, Jason, Schatz, Michael C., Philippakis, Anthony A., Afgan, Enis, Banks, Eric, Carey, Vincent J., Carroll, Robert J., Culotti, Alessandro, Ellrott, Kyle, Goecks, Jeremy, Grossman, Robert L., Hall, Ira M., Hansen, Kasper D., Lawson, Jonathan, Leek, Jeffrey T., Luria, Anne O’Donnell, Mosher, Stephen, Morgan, Martin, Nekrutenko, Anton, O’Connor, Brian D., Osborn, Kevin, Paten, Benedict, Patterson, Candace, Tan, Frederick J., Taylor, Casey Overby, Vessio, Jennifer, Waldron, Levi, Wang, Ting, and Wuichet, Kristin

Published
2022
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14. Author Correction: Community-wide hackathons to identify central themes in single-cell multi-omics

Author

Cao, Kim-Anh Lê, Abadi, Al J., Davis-Marcisak, Emily F., Hsu, Lauren, Arora, Arshi, Coullomb, Alexis, Deshpande, Atul, Feng, Yuzhou, Jeganathan, Pratheepa, Loth, Melanie, Meng, Chen, Mu, Wancen, Pancaldi, Vera, Sankaran, Kris, Righelli, Dario, Singh, Amrit, Sodicoff, Joshua S., Stein-O’Brien, Genevieve L., Subramanian, Ayshwarya, Welch, Joshua D., You, Yue, Argelaguet, Ricard, Carey, Vincent J., Dries, Ruben, Greene, Casey S., Holmes, Susan, Love, Michael I., Ritchie, Matthew E., Yuan, Guo-Cheng, Culhane, Aedin C., and Fertig, Elana

Published
2021
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15. Community-wide hackathons to identify central themes in single-cell multi-omics

Author

Lê Cao, Kim-Anh, Abadi, Al J., Davis-Marcisak, Emily F., Hsu, Lauren, Arora, Arshi, Coullomb, Alexis, Deshpande, Atul, Feng, Yuzhou, Jeganathan, Pratheepa, Loth, Melanie, Meng, Chen, Mu, Wancen, Pancaldi, Vera, Sankaran, Kris, Righelli, Dario, Singh, Amrit, Sodicoff, Joshua S., Stein-O’Brien, Genevieve L., Subramanian, Ayshwarya, Welch, Joshua D., You, Yue, Argelaguet, Ricard, Carey, Vincent J., Dries, Ruben, Greene, Casey S., Holmes, Susan, Love, Michael I., Ritchie, Matthew E., Yuan, Guo-Cheng, Culhane, Aedin C., and Fertig, Elana

Published
2021
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16. Genome-wide interaction studies reveal sex-specific asthma risk alleles

Author

Myers, Rachel A, Scott, Nicole M, Gauderman, W James, Qiu, Weiliang, Mathias, Rasika A, Romieu, Isabelle, Levin, Albert M, Pino-Yanes, Maria, Graves, Penelope E, Villarreal, Albino Barraza, Beaty, Terri H, Carey, Vincent J, Croteau-Chonka, Damien C, del Rio Navarro, Blanca, Edlund, Christopher, Hernandez-Cadena, Leticia, Navarro-Olivos, Efrain, Padhukasahasram, Badri, Salam, Muhammad T, Torgerson, Dara G, Van den Berg, David J, Vora, Hita, Bleecker, Eugene R, Meyers, Deborah A, Williams, L Keoki, Martinez, Fernando D, Burchard, Esteban G, Barnes, Kathleen C, Gilliland, Frank D, Weiss, Scott T, London, Stephanie J, Raby, Benjamin A, Ober, Carole, Nicolae, Dan L, Santana, Jose Rodriguez, Cintron, William Rodriguez, Chapela, Rocio, Ford, Jean, Thyne, Shannon, Avila, Pedro C, Monge, Juan Jose Sienra, Boorgula, Meher, Cheadle, Chris, Eng, Celeste S, Kiley, J, Banks-Schlegel, S, and Gan, W

Subjects
Biological Sciences, Genetics, Clinical Research, Human Genome, Lung, Prevention, Asthma, Aetiology, 2.1 Biological and endogenous factors, Inflammatory and immune system, Respiratory, Alleles, Chromosome Mapping, Female, Gene Expression Regulation, Genetic Loci, Genetic Predisposition to Disease, Genome-Wide Association Study, Genotype, Humans, Male, Odds Ratio, Polymorphism, Single Nucleotide, Quantitative Trait Loci, Racial Groups, Reproducibility of Results, Sex Factors, GRAAD, Continental Population Groups, Medical and Health Sciences, Genetics & Heredity
Abstract

Asthma is a complex disease with sex-specific differences in prevalence. Candidate gene studies have suggested that genotype-by-sex interaction effects on asthma risk exist, but this has not yet been explored at a genome-wide level. We aimed to identify sex-specific asthma risk alleles by performing a genome-wide scan for genotype-by-sex interactions in the ethnically diverse participants in the EVE Asthma Genetics Consortium. We performed male- and female-specific genome-wide association studies in 2653 male asthma cases, 2566 female asthma cases and 3830 non-asthma controls from European American, African American, African Caribbean and Latino populations. Association tests were conducted in each study sample, and the results were combined in ancestry-specific and cross-ancestry meta-analyses. Six sex-specific asthma risk loci had P-values < 1 × 10(-6), of which two were male specific and four were female specific; all were ancestry specific. The most significant sex-specific association in European Americans was at the interferon regulatory factor 1 (IRF1) locus on 5q31.1. We also identify a Latino female-specific association in RAP1GAP2. Both of these loci included single-nucleotide polymorphisms that are known expression quantitative trait loci and have been associated with asthma in independent studies. The IRF1 locus is a strong candidate region for male-specific asthma susceptibility due to the association and validation we demonstrate here, the known role of IRF1 in asthma-relevant immune pathways and prior reports of sex-specific differences in interferon responses.

Published
2014

18. Trial of the MIND Diet for Prevention of Cognitive Decline in Older Persons

Author

Barnes, Lisa L., primary, Dhana, Klodian, additional, Liu, Xiaoran, additional, Carey, Vincent J., additional, Ventrelle, Jennifer, additional, Johnson, Kathleen, additional, Hollings, Chiquia S., additional, Bishop, Louise, additional, Laranjo, Nancy, additional, Stubbs, Benjamin J., additional, Reilly, Xavier, additional, Agarwal, Puja, additional, Zhang, Shengwei, additional, Grodstein, Francine, additional, Tangney, Christy C., additional, Holland, Thomas M., additional, Aggarwal, Neelum T., additional, Arfanakis, Konstantinos, additional, Morris, Martha Clare, additional, and Sacks, Frank M., additional

Published
2023
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19. The Association of Maternal Asthma and Early Pregnancy Vitamin D with Risk of Preeclampsia: An Observation From Vitamin D Antenatal Asthma Reduction Trial (VDAART)

Author

Mirzakhani, Hooman, Carey, Vincent J., McElrath, Thomas F., Laranjo, Nancy, O'Connor, George, Iverson, Ronald E., Lee-Parritz, Aviva, Strunk, Robert C., Bacharier, Leonard B., Macones, George A., Zeiger, Robert S., Schatz, Michael, Hollis, Bruce W., Litonjua, Augusto A., and Weiss, Scott T.

Published
2018
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23. The relationship of fetal sex and maternal race and ethnicity with early and late pregnancy C‐reactive protein and interleukin‐8

Author

Jha, Anjali, primary, Baumann, Noah, additional, Shadid, Iskander, additional, Shah, Jhill, additional, Chen, Yih‐Chieh S., additional, Lee‐Sarwar, Kathleen A., additional, Zeiger, Robert S., additional, O'Connor, George T., additional, Bacharier, Leonard B., additional, Carey, Vincent J., additional, Laranjo, Nancy, additional, Fichorova, Raina N., additional, Litonjua, Augusto A., additional, Weiss, Scott T., additional, and Mirzakhani, Hooman, additional

Published
2023
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24. Omega-3 Fatty Acids Interact with DPP10 Region Genotype in Association with Childhood Atopy

Author

Lee-Sarwar, Kathleen A., primary, Fischer-Rasmussen, Kasper, additional, Bønnelykke, Klaus, additional, Bisgaard, Hans, additional, Chawes, Bo, additional, Kelly, Rachel S., additional, Lasky-Su, Jessica, additional, Zeiger, Robert S., additional, O’Connor, George T., additional, Bacharier, Leonard B., additional, Carey, Vincent J., additional, Laranjo, Nancy, additional, Litonjua, Augusto A., additional, and Weiss, Scott T., additional

Published
2023
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29. Bioconductor: open software development for computational biology and bioinformatics

Author

Gentleman, Robert C, Carey, Vincent J, Bates, Douglas M, Bolstad, Ben, Dettling, Marcel, Dudoit, Sandrine, Ellis, Byron, Gautier, Laurent, Ge, Yongchao, Gentry, Jeff, Hornik, Kurt, Hothorn, Torsten, Huber, Wolfgang, Iacus, Stefano, Irizarry, Rafael, Leisch, Friedrich, Li, Cheng, Maechler, Martin, Rossini, Anthony J, Sawitzki, Gunther, Smith, Colin, Smyth, Gordon, Tierney, Luke, Yang, Jean YH, and Zhang, Jianhua

Subjects
Bioengineering, Networking and Information Technology R&D (NITRD), Computational Biology, Internet, Reproducibility of Results, Software, Genomic data, microarray, Environmental Sciences, Biological Sciences, Information and Computing Sciences, Bioinformatics
Abstract

The Bioconductor project is an initiative for the collaborative creation of extensible software for computational biology and bioinformatics. The goals of the project include: fostering collaborative development and widespread use of innovative software, reducing barriers to entry into interdisciplinary scientific research, and promoting the achievement of remote reproducibility of research results. We describe details of our aims and methods, identify current challenges, compare Bioconductor to other open bioinformatics projects, and provide working examples.

Published
2004

30. Gastric and Duodenal Safety of Daily Alendronate

Author

Donahue, James G, Chan, K Arnold, Andrade, Susan E, Beck, Arne, Boles, Myde, Buist, Diana SM, Carey, Vincent J, Chandler, Julie M, Chase, Gary A, Ettinger, Bruce, Fishman, Paul, Goodman, Michael, Guess, Harry A, Gurwitz, Jerry H, LaCroix, Andrea Z, Levin, TR, and Platt, Richard

Subjects
Digestive Diseases, Aging, Clinical Research, Osteoporosis, Adult, Aged, Aged, 80 and over, Alendronate, Cohort Studies, Duodenal Diseases, Duodenal Ulcer, Female, Gastrointestinal Hemorrhage, Hospitalization, Humans, Intestinal Perforation, Male, Middle Aged, Retrospective Studies, Risk Assessment, Stomach Ulcer, Clinical Sciences, Opthalmology and Optometry, Public Health and Health Services
Abstract

BackgroundIsolated case reports of gastric ulcers after alendronate sodium use raised concern about the gastroduodenal safety of daily alendronate. This study was conducted to estimate the excess risk of hospitalizations for gastric or duodenal perforations, ulcers, and bleeding associated with alendronate use.Participants and methodsStudy subjects were 6432 men and women, 35 years or older. The subjects were members of 8 health maintenance organizations who were dispensed alendronate from October 1995 through September 1997. There was also a group of 33 176 age-, sex-, and health maintenance organization-matched unexposed persons. Because of concerns that osteoporosis might confound the association between alendronate use and perforation, ulcer, or bleeding, a second comparison group of 9776 women, 60 years or older, who had osteoporotic fractures was assembled. Hospitalizations for gastroduodenal events were identified by discharge diagnosis codes in automated claims records, and confirmed by manual record review.ResultsBased on the 14 confirmed events in the alendronate group and 35 in the unexposed group, the crude incidence rate ratio of gastroduodenal perforation, ulcer, or bleeding for the alendronate cohort was 3.0. The incidence rate ratio was 1.8 (95% confidence interval, 0.8-3.9) after control for prior hospitalizations, comorbidity, and recent exposure to prescription nonsteroidal anti-inflammatory drugs and oral corticosteroids. The crude incidence ratio rate for the age, sex, and health maintenance organizations-restricted cohort of alendronate users relative to the fracture cohort was 1.1 and the adjusted incidence rate ratio was 1.1 (95% confidence interval, 0.6-2.2).ConclusionsOsteoporosis and related factors appear to play an important role in the relationship between alendronate use and confirmed gastroduodenal perforation, ulcer, or bleeding; a substantial fraction of the increased risk we observed for alendronate users in the unadjusted analysis was the result of confounding.

Published
2002

31. Omega-3 Fatty Acids Interact with DPP10 Region Genotype in Association with Childhood Atopy

Author

Lee-Sarwar, Kathleen A., Fischer-Rasmussen, Kasper, Bønnelykke, Klaus, Bisgaard, Hans, Chawes, Bo, Kelly, Rachel S., Lasky-Su, Jessica, Zeiger, Robert S., O’Connor, George T., Bacharier, Leonard B., Carey, Vincent J., Laranjo, Nancy, Litonjua, Augusto A., Weiss, Scott T., Lee-Sarwar, Kathleen A., Fischer-Rasmussen, Kasper, Bønnelykke, Klaus, Bisgaard, Hans, Chawes, Bo, Kelly, Rachel S., Lasky-Su, Jessica, Zeiger, Robert S., O’Connor, George T., Bacharier, Leonard B., Carey, Vincent J., Laranjo, Nancy, Litonjua, Augusto A., and Weiss, Scott T.

Abstract

Associations of omega-3 fatty acids (n-3) with allergic diseases are inconsistent, perhaps in part due to genetic variation. We sought to identify and validate genetic variants that modify associations of n-3 with childhood asthma or atopy in participants in the Vitamin D Antenatal Asthma Reduction Trial (VDAART) and the Copenhagen Prospective Studies on Asthma in Childhood 2010 (COPSAC). Dietary n-3 was derived from food frequency questionnaires and plasma n-3 was measured via untargeted mass spectrometry in early childhood and children aged 6 years old. Interactions of genotype with n-3 in association with asthma or atopy at age 6 years were sought for six candidate genes/gene regions and genome-wide. Two SNPs in the region of DPP10 (rs958457 and rs1516311) interacted with plasma n-3 at age 3 years in VDAART (p = 0.007 and 0.003, respectively) and with plasma n-3 at age 18 months in COPSAC (p = 0.01 and 0.02, respectively) in associationwith atopy. Another DPP10 region SNP, rs1367180, interacted with dietary n-3 at age 6 years in VDAART (p = 0.009) and with plasma n-3 at age 6 years in COPSAC (p = 0.004) in association with atopy. No replicated interactions were identified for asthma. The effect of n-3 on reducing childhood allergic disease may differ by individual factors, including genetic variation in the DPP10 region.

Published
2023

32. The maternal prenatal and offspring early-life gut microbiome of childhood asthma phenotypes

Author

Lee-Sarwar, Kathleen A., Chen, Yih Chieh, Chen, Yuan Yao, Kozyrskyj, Anita L, Mandhane, Piush J., Turvey, Stuart E., Subbarao, Padmaja, Bisgaard, Hans, Stokholm, Jakob, Chawes, Bo, Sørensen, Søren J., Kelly, Rachel S, Lasky-Su, Jessica, Zeiger, Robert S., O'Connor, George T., Sandel, Megan T., Bacharier, Leonard B., Beigelman, Avraham, Carey, Vincent J, Harshfield, Benjamin J., Laranjo, Nancy, Gold, Diane R., Weiss, Scott T, Litonjua, Augusto A., Lee-Sarwar, Kathleen A., Chen, Yih Chieh, Chen, Yuan Yao, Kozyrskyj, Anita L, Mandhane, Piush J., Turvey, Stuart E., Subbarao, Padmaja, Bisgaard, Hans, Stokholm, Jakob, Chawes, Bo, Sørensen, Søren J., Kelly, Rachel S, Lasky-Su, Jessica, Zeiger, Robert S., O'Connor, George T., Sandel, Megan T., Bacharier, Leonard B., Beigelman, Avraham, Carey, Vincent J, Harshfield, Benjamin J., Laranjo, Nancy, Gold, Diane R., Weiss, Scott T, and Litonjua, Augusto A.

Abstract

Background: The infant fecal microbiome is known to impact subsequent asthma risk, but the environmental exposures impacting this association, the role of the maternal microbiome, and how the microbiome impacts different childhood asthma phenotypes are unknown. Methods: Our objective was to identify associations between features of the prenatal and early-life fecal microbiomes and child asthma phenotypes. We analyzed fecal 16 s rRNA microbiome profiling and fecal metabolomic profiling from stool samples collected from mothers during the third trimester of pregnancy (n = 120) and offspring at ages 3–6 months (n = 265), 1 (n = 436) and 3 years (n = 506) in a total of 657 mother–child pairs participating in the Vitamin D Antenatal Asthma Reduction Trial. We used clinical data from birth to age 6 years to characterize subjects with asthma as having early, transient or active asthma phenotypes. In addition to identifying specific genera that were robustly associated with asthma phenotypes in multiple covariate-adjusted models, we clustered subjects by their longitudinal microbiome composition and sought associations between fecal metabolites and relevant microbiome and clinical features. Results: Seven maternal and two infant fecal microbial taxa were robustly associated with at least one asthma phenotype, and a longitudinal gut microenvironment profile was associated with early asthma (Fisher exact test p =.03). Though mode of delivery was not directly associated with asthma, we found substantial evidence for a pathway whereby cesarean section reduces fecal Bacteroides and microbial sphingolipids, increasing susceptibility to early asthma. Conclusion: Overall, our results suggest that the early-life, including prenatal, fecal microbiome modifies risk of asthma, especially asthma with onset by age 3 years.

Published
2023

33. Maternal vitamin D status modifies the effects of early life tobacco exposure on child lung function

Author

Knihtilä, Hanna M., primary, Huang, Mengna, additional, Prince, Nicole, additional, Stubbs, Benjamin J., additional, Carey, Vincent J., additional, Laranjo, Nancy, additional, Mirzakhani, Hooman, additional, Zeiger, Robert S., additional, Bacharier, Leonard B., additional, O’Connor, George T., additional, Litonjua, Augusto A., additional, Weiss, Scott T., additional, and Lasky-Su, Jessica, additional

Published
2022
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34. Integration of metabolomic and transcriptomic networks in pregnant women reveals biological pathways and predictive signatures associated with preeclampsia

Author

Kelly, Rachel S., Croteau-Chonka, Damien C., Dahlin, Amber, Mirzakhani, Hooman, Wu, Ann C., Wan, Emily S., McGeachie, Michael J., Qiu, Weiliang, Sordillo, Joanne E., Al-Garawi, Amal, Gray, Kathryn J., McElrath, Thomas F., Carey, Vincent J., Clish, Clary B., Litonjua, Augusto A., Weiss, Scott T., and Lasky-Su, Jessica A.

Published
2017
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35. A genome-wide survey of CD4+ lymphocyte regulatory genetic variants identifies novel asthma genes

Author

Sharma, Sunita, Zhou, Xiaobo, Thibault, Derek M., Himes, Blanca E., Liu, Andy, Szefler, Stanley J., Strunk, Robert, Castro, Mario, Hansel, Nadia N., Diette, Gregory B., Vonakis, Becky M., Adkinson, N. Franklin, Jr., Avila, Lydiana, Soto-Quiros, Manuel, Barraza-Villareal, Albino, Lemanske, Robert F., Jr., Solway, Julian, Krishnan, Jerry, White, Steven R., Cheadle, Chris, Berger, Alan E., Fan, Jinshui, Boorgula, Meher Preethi, Nicolae, Dan, Gilliland, Frank, Barnes, Kathleen, London, Stephanie J., Martinez, Fernando, Ober, Carole, Celedón, Juan C., Carey, Vincent J., Weiss, Scott T., and Raby, Benjamin A.

Published
2014
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37. The maternal prenatal and offspring early‐life gut microbiome of childhood asthma phenotypes

Author

Lee‐Sarwar, Kathleen A., primary, Chen, Yih‐Chieh, additional, Chen, Yuan Yao, additional, Kozyrskyj, Anita L., additional, Mandhane, Piush J., additional, Turvey, Stuart E., additional, Subbarao, Padmaja, additional, Bisgaard, Hans, additional, Stokholm, Jakob, additional, Chawes, Bo, additional, Sørensen, Søren J., additional, Kelly, Rachel S., additional, Lasky‐Su, Jessica, additional, Zeiger, Robert S., additional, O'Connor, George T., additional, Sandel, Megan T., additional, Bacharier, Leonard B., additional, Beigelman, Avraham, additional, Carey, Vincent J., additional, Harshfield, Benjamin J., additional, Laranjo, Nancy, additional, Gold, Diane R., additional, Weiss, Scott T., additional, and Litonjua, Augusto A., additional

Published
2022
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42. Universality of human microbial dynamics

Author

Bashan, Amir, Gibson, Travis E., Friedman, Jonathan, Carey, Vincent J., Weiss, Scott T., Hohmann, Elizabeth L., and Liu, Yang-Yu

Subjects
Microbiota (Symbiotic organisms) -- Research, Microbial populations -- Research, Microbiological research, Environmental issues, Science and technology, Zoology and wildlife conservation
Abstract

Human-associated microbial communities have a crucial role in determining our health and well-being (1,2), and this has led to the continuing development of microbiome-based therapies (3) such as faecal microbiota transplantation (4,5). These microbial communities are very complex, dynamic6 and highly personalized ecosystems (3,7), exhibiting a high degree of inter-individual variability in both species assemblages (8) and abundance profiles (9). It is not known whether the underlying ecological dynamics of these communities, which can be parameterized by growth rates, and intra-and inter-species interactions in population dynamics models (10), are largely host-independent (that is, universal) or host-specific. If the inter-individual variability reflects host-specific dynamics due to differences in host lifestyle (11), physiology (12) or genetics (13), then generic microbiome manipulations may have unintended consequences, rendering them ineffective or even detrimental. Alternatively, microbial ecosystems of different subjects may exhibit universal dynamics, with the inter-individual variability mainly originating from differences in the sets of colonizing species (7,14). Here we develop a new computational method to characterize human microbial dynamics. By applying this method to cross-sectional data from two large-scale metagenomic studies-the Human Microbiome Project (9,15) and the Student Microbiome Project (16)--we show that gut and mouth microbiomes display pronounced universal dynamics, whereas communities associated with certain skin sites are probably shaped by differences in the host environment. Notably, the universality of gut microbial dynamics is not observed in subjects with recurrent Clostridium difficile infection (17) but is observed in the same set of subjects after faecal microbiota transplantation. These results fundamentally improve our understanding of the processes that shape human microbial ecosystems, and pave the way to designing general microbiome-based therapies (18)., The underlying dynamics of a microbial ecosystem, that is, the ecological interactions that govern its change, equilibrium and stability, can be represented by a population dynamic model [[??].sup.(v)] = f [...]

Published
2016

43. R Language

Author

Gentleman, Robert, Huber, Wolfgang, Carey, Vincent J., and Lovric, Miodrag, editor

Published
2011
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45. Gene Expression Profiling in Blood Provides Reproducible Molecular Insights into Asthma Control

Author

Croteau-Chonka, Damien C., Qiu, Weiliang, Martinez, Fernando D., Strunk, Robert C., Lemanske, Robert F., Jr., Liu, Andrew H., Gilliland, Frank D., Millstein, Joshua, Gauderman, James W., Ober, Carole, Krishnan, Jerry A., White, Steven R., Naureckas, Edward T., Nicolae, Dan L., Barnes, Kathleen C., London, Stephanie J., Barraza-Villarreal, Albino, Carey, Vincent J., Weiss, Scott T., and Raby, Benjamin A.

Published
2017
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46. The maternal prenatal and offspring early‐life gut microbiome of childhood asthma phenotypes.

Author

Lee‐Sarwar, Kathleen A., Chen, Yih‐Chieh, Chen, Yuan Yao, Kozyrskyj, Anita L., Mandhane, Piush J., Turvey, Stuart E., Subbarao, Padmaja, Bisgaard, Hans, Stokholm, Jakob, Chawes, Bo, Sørensen, Søren J., Kelly, Rachel S., Lasky‐Su, Jessica, Zeiger, Robert S., O'Connor, George T., Sandel, Megan T., Bacharier, Leonard B., Beigelman, Avraham, Carey, Vincent J., and Harshfield, Benjamin J.

Subjects
ASTHMA in children, GUT microbiome, THIRD trimester of pregnancy, CESAREAN section, FISHER exact test
Abstract

Background: The infant fecal microbiome is known to impact subsequent asthma risk, but the environmental exposures impacting this association, the role of the maternal microbiome, and how the microbiome impacts different childhood asthma phenotypes are unknown. Methods: Our objective was to identify associations between features of the prenatal and early‐life fecal microbiomes and child asthma phenotypes. We analyzed fecal 16 s rRNA microbiome profiling and fecal metabolomic profiling from stool samples collected from mothers during the third trimester of pregnancy (n = 120) and offspring at ages 3–6 months (n = 265), 1 (n = 436) and 3 years (n = 506) in a total of 657 mother–child pairs participating in the Vitamin D Antenatal Asthma Reduction Trial. We used clinical data from birth to age 6 years to characterize subjects with asthma as having early, transient or active asthma phenotypes. In addition to identifying specific genera that were robustly associated with asthma phenotypes in multiple covariate‐adjusted models, we clustered subjects by their longitudinal microbiome composition and sought associations between fecal metabolites and relevant microbiome and clinical features. Results: Seven maternal and two infant fecal microbial taxa were robustly associated with at least one asthma phenotype, and a longitudinal gut microenvironment profile was associated with early asthma (Fisher exact test p =.03). Though mode of delivery was not directly associated with asthma, we found substantial evidence for a pathway whereby cesarean section reduces fecal Bacteroides and microbial sphingolipids, increasing susceptibility to early asthma. Conclusion: Overall, our results suggest that the early‐life, including prenatal, fecal microbiome modifies risk of asthma, especially asthma with onset by age 3 years. [ABSTRACT FROM AUTHOR]

Published
2023
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48. Vitamin D supplementation in pregnancy, prenatal 25(OH)D levels, race, and subsequent asthma or recurrent wheeze in offspring: Secondary analyses from the Vitamin D Antenatal Asthma Reduction Trial

Author

Wolsk, Helene M., Harshfield, Benjamin J., Laranjo, Nancy, Carey, Vincent J., O’Connor, George, Sandel, Megan, Strunk, Robert C., Bacharier, Leonard B., Zeiger, Robert S., Schatz, Michael, Hollis, Bruce W., Weiss, Scott T., and Litonjua, Augusto A.

Published
2017
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