Search

Your search keyword '"Manion, Frank J."' showing total 50 results
Start Over Author "Manion, Frank J."
50 results on '"Manion, Frank J."'

2. Expressing and Executing Informed Consent Permissions Using SWRL: The All of Us Use Case

Author

Amith, Muhammad, Harris, Marcelline R., Stansbury, Cooper, Ford, Kathleen, Manion, Frank J., and Tao, Cui

Subjects
Computer Science - Digital Libraries, F.4, H.4, E.2, I.7, H.5, A.m
Abstract

The informed consent process is a complicated procedure involving permissions as well a variety of entities and actions. In this paper, we discuss the use of Semantic Web Rule Language (SWRL) to further extend the Informed Consent Ontology (ICO) to allow for semantic machine-based reasoning to manage and generate important permission-based information that can later be viewed by stakeholders. We present four use cases of permissions from the All of Us informed consent document and translate these permissions into SWRL expressions to extend and operationalize ICO. Our efforts show how SWRL is able to infer some of the implicit information based on the defined rules, and demonstrate the utility of ICO through the use of SWRL extensions. Future work will include developing formal and generalized rules and expressing permissions from the entire document, as well as working towards integrating ICO into software systems to enhance the semantic representation of informed consent for biomedical research., Comment: To appear in: Proceedings of the American Medical Informatics Associations (AMIA) 2021 Annual Symposium Oct 30-Nov 03 San Diego, CA, USA. Please visit and cite the canonical version once available. M Amith and M Harris contributed equally to this work

Published
2021

5. Granularly, Precisely, and Timely: Leveraging Large Language Models for Safety and Efficacy Extraction in Oncology Clinical Trial Abstracts (SEETrials)

Author

Paek, Hunki, primary, Lee, Kyeryoung, additional, Datta, Surabhi, additional, Huang, Liang-Chin, additional, Higashi, Josh, additional, Ofoegbu, Nneka, additional, Wang, Jingqi, additional, Manion, Frank J, additional, Warner, Jeremy L, additional, Xu, Hua, additional, and Wang, Xiaoyan, additional

Published
2024
Full Text
View/download PDF

6. Corrigendum: genome-wide association study of colorectal cancer identifies six new susceptibility loci.

Author

Schumacher, Fredrick R, Schmit, Stephanie L, Jiao, Shuo, Edlund, Christopher K, Wang, Hansong, Zhang, Ben, Hsu, Li, Huang, Shu-Chen, Fischer, Christopher P, Harju, John F, Idos, Gregory E, Lejbkowicz, Flavio, Manion, Frank J, McDonnell, Kevin, McNeil, Caroline E, Melas, Marilena, Rennert, Hedy S, Shi, Wei, Thomas, Duncan C, Van Den Berg, David J, Hutter, Carolyn M, Aragaki, Aaron K, Butterbach, Katja, Caan, Bette J, Carlson, Christopher S, Chanock, Stephen J, Curtis, Keith R, Fuchs, Charles S, Gala, Manish, Giovannucci, Edward L, Gogarten, Stephanie M, Hayes, Richard B, Henderson, Brian, Hunter, David J, Jackson, Rebecca D, Kolonel, Laurence N, Kooperberg, Charles, Küry, Sébastien, LaCroix, Andrea, Laurie, Cathy C, Laurie, Cecelia A, Lemire, Mathieu, Levine, David, Ma, Jing, Makar, Karen W, Qu, Conghui, Taverna, Darin, Ulrich, Cornelia M, Wu, Kana, Kono, Suminori, West, Dee W, Berndt, Sonja I, Bezieau, Stephane, Brenner, Hermann, Campbell, Peter T, Chan, Andrew T, Chang-Claude, Jenny, Coetzee, Gerhard A, Conti, David V, Duggan, David, Figueiredo, Jane C, Fortini, Barbara K, Gallinger, Steven J, Gauderman, W James, Giles, Graham, Green, Roger, Haile, Robert, Harrison, Tabitha A, Hoffmeister, Michael, Hopper, John L, Hudson, Thomas J, Jacobs, Eric, Iwasaki, Motoki, Jee, Sun Ha, Jenkins, Mark, Jia, Wei-Hua, Joshi, Amit, Li, Li, Lindor, Noralene M, Matsuo, Keitaro, Moreno, Victor, Mukherjee, Bhramar, Newcomb, Polly A, Potter, John D, Raskin, Leon, Rennert, Gad, Rosse, Stephanie, Severi, Gianluca, Schoen, Robert E, Seminara, Daniela, Shu, Xiao-Ou, Slattery, Martha L, Tsugane, Shoichiro, White, Emily, Xiang, Yong-Bing, Zanke, Brent W, Zheng, Wei, Le Marchand, Loic, Casey, Graham, and Gruber, Stephen B

Subjects
MD Multidisciplinary
Published
2015

7. Erratum: Corrigendum: Genome-wide association study of colorectal cancer identifies six new susceptibility loci

Author

Schumacher, Fredrick R, Schmit, Stephanie L, Jiao, Shuo, Edlund, Christopher K, Wang, Hansong, Zhang, Ben, Hsu, Li, Huang, Shu-Chen, Fischer, Christopher P, Harju, John F, Idos, Gregory E, Lejbkowicz, Flavio, Manion, Frank J, McDonnell, Kevin, McNeil, Caroline E, Melas, Marilena, Rennert, Hedy S, Shi, Wei, Thomas, Duncan C, Van Den Berg, David J, Hutter, Carolyn M, Aragaki, Aaron K, Butterbach, Katja, Caan, Bette J, Carlson, Christopher S, Chanock, Stephen J, Curtis, Keith R, Fuchs, Charles S, Gala, Manish, Giovannucci, Edward L, Gogarten, Stephanie M, Hayes, Richard B, Henderson, Brian, Hunter, David J, Jackson, Rebecca D, Kolonel, Laurence N, Kooperberg, Charles, Küry, Sébastien, LaCroix, Andrea, Laurie, Cathy C, Laurie, Cecelia A, Lemire, Mathieu, Levine, David, Ma, Jing, Makar, Karen W, Qu, Conghui, Taverna, Darin, Ulrich, Cornelia M, Wu, Kana, Kono, Suminori, West, Dee W, Berndt, Sonja I, Bezieau, Stephane, Brenner, Hermann, Campbell, Peter T, Chan, Andrew T, Chang-Claude, Jenny, Coetzee, Gerhard A, Conti, David V, Duggan, David, Figueiredo, Jane C, Fortini, Barbara K, Gallinger, Steven J, Gauderman, W James, Giles, Graham, Green, Roger, Haile, Robert, Harrison, Tabitha A, Hoffmeister, Michael, Hopper, John L, Hudson, Thomas J, Jacobs, Eric, Iwasaki, Motoki, Jee, Sun Ha, Jenkins, Mark, Jia, Wei-Hua, Joshi, Amit, Li, Li, Lindor, Noralene M, Matsuo, Keitaro, Moreno, Victor, Mukherjee, Bhramar, Newcomb, Polly A, Potter, John D, Raskin, Leon, Rennert, Gad, Rosse, Stephanie, Severi, Gianluca, Schoen, Robert E, Seminara, Daniela, Shu, Xiao-Ou, Slattery, Martha L, Tsugane, Shoichiro, White, Emily, Xiang, Yong-Bing, Zanke, Brent W, Zheng, Wei, Le Marchand, Loic, Casey, Graham, and Gruber, Stephen B

Subjects
Biological Sciences, Biomedical and Clinical Sciences, Oncology and Carcinogenesis, Digestive Diseases, Cancer, Colo-Rectal Cancer
Published
2015

8. Genome-wide association study of colorectal cancer identifies six new susceptibility loci.

Author

Schumacher, Fredrick R, Schmit, Stephanie L, Jiao, Shuo, Edlund, Christopher K, Wang, Hansong, Zhang, Ben, Hsu, Li, Huang, Shu-Chen, Fischer, Christopher P, Harju, John F, Idos, Gregory E, Lejbkowicz, Flavio, Manion, Frank J, McDonnell, Kevin, McNeil, Caroline E, Melas, Marilena, Rennert, Hedy S, Shi, Wei, Thomas, Duncan C, Van Den Berg, David J, Hutter, Carolyn M, Aragaki, Aaron K, Butterbach, Katja, Caan, Bette J, Carlson, Christopher S, Chanock, Stephen J, Curtis, Keith R, Fuchs, Charles S, Gala, Manish, Giovannucci, Edward L, Gogarten, Stephanie M, Hayes, Richard B, Henderson, Brian, Hunter, David J, Jackson, Rebecca D, Kolonel, Laurence N, Kooperberg, Charles, Küry, Sébastien, LaCroix, Andrea, Laurie, Cathy C, Laurie, Cecelia A, Lemire, Mathieu, Levine, David, Ma, Jing, Makar, Karen W, Qu, Conghui, Taverna, Darin, Ulrich, Cornelia M, Wu, Kana, Kono, Suminori, West, Dee W, Berndt, Sonja I, Bezieau, Stéphane, Brenner, Hermann, Campbell, Peter T, Chan, Andrew T, Chang-Claude, Jenny, Coetzee, Gerhard A, Conti, David V, Duggan, David, Figueiredo, Jane C, Fortini, Barbara K, Gallinger, Steven J, Gauderman, W James, Giles, Graham, Green, Roger, Haile, Robert, Harrison, Tabitha A, Hoffmeister, Michael, Hopper, John L, Hudson, Thomas J, Jacobs, Eric, Iwasaki, Motoki, Jee, Sun Ha, Jenkins, Mark, Jia, Wei-Hua, Joshi, Amit, Li, Li, Lindor, Noralene M, Matsuo, Keitaro, Moreno, Victor, Mukherjee, Bhramar, Newcomb, Polly A, Potter, John D, Raskin, Leon, Rennert, Gad, Rosse, Stephanie, Severi, Gianluca, Schoen, Robert E, Seminara, Daniela, Shu, Xiao-Ou, Slattery, Martha L, Tsugane, Shoichiro, White, Emily, Xiang, Yong-Bing, Zanke, Brent W, and Zheng, Wei

Subjects
Humans, Colorectal Neoplasms, Genetic Predisposition to Disease, Odds Ratio, Case-Control Studies, Polymorphism, Single Nucleotide, Genome-Wide Association Study, Genetics, Digestive Diseases, Prevention, Cancer, Human Genome, Colo-Rectal Cancer, 2.1 Biological and endogenous factors, MD Multidisciplinary
Abstract

Genetic susceptibility to colorectal cancer is caused by rare pathogenic mutations and common genetic variants that contribute to familial risk. Here we report the results of a two-stage association study with 18,299 cases of colorectal cancer and 19,656 controls, with follow-up of the most statistically significant genetic loci in 4,725 cases and 9,969 controls from two Asian consortia. We describe six new susceptibility loci reaching a genome-wide threshold of P

Published
2015

10. AutoCriteria: a generalizable clinical trial eligibility criteria extraction system powered by large language models.

Author

Datta, Surabhi, Lee, Kyeryoung, Paek, Hunki, Manion, Frank J, Ofoegbu, Nneka, Du, Jingcheng, Li, Ying, Huang, Liang-Chin, Wang, Jingqi, Lin, Bin, Xu, Hua, and Wang, Xiaoyan

Abstract

Objectives We aim to build a generalizable information extraction system leveraging large language models to extract granular eligibility criteria information for diverse diseases from free text clinical trial protocol documents. We investigate the model's capability to extract criteria entities along with contextual attributes including values, temporality, and modifiers and present the strengths and limitations of this system. Materials and Methods The clinical trial data were acquired from https://ClinicalTrials.gov/. We developed a system, AutoCriteria, which comprises the following modules: preprocessing, knowledge ingestion, prompt modeling based on GPT, postprocessing, and interim evaluation. The final system evaluation was performed, both quantitatively and qualitatively, on 180 manually annotated trials encompassing 9 diseases. Results AutoCriteria achieves an overall F1 score of 89.42 across all 9 diseases in extracting the criteria entities, with the highest being 95.44 for nonalcoholic steatohepatitis and the lowest of 84.10 for breast cancer. Its overall accuracy is 78.95% in identifying all contextual information across all diseases. Our thematic analysis indicated accurate logic interpretation of criteria as one of the strengths and overlooking/neglecting the main criteria as one of the weaknesses of AutoCriteria. Discussion AutoCriteria demonstrates strong potential to extract granular eligibility criteria information from trial documents without requiring manual annotations. The prompts developed for AutoCriteria generalize well across different disease areas. Our evaluation suggests that the system handles complex scenarios including multiple arm conditions and logics. Conclusion AutoCriteria currently encompasses a diverse range of diseases and holds potential to extend to more in the future. This signifies a generalizable and scalable solution, poised to address the complexities of clinical trial application in real-world settings. [ABSTRACT FROM AUTHOR]

Published
2024
Full Text
View/download PDF

11. Investigating the genetic relationship between Alzheimer’s disease and cancer using GWAS summary statistics

Author

Feng, Yen-Chen Anne, Cho, Kelly, Lindstrom, Sara, Kraft, Peter, Cormack, Jean, Liang, Liming, Driver, Jane A., Blalock, Kendra, Campbell, Peter T., Casey, Graham, Conti, David V., Edlund, Christopher K., Figueiredo, Jane, James Gauderman, W., Gong, Jian, Green, Roger C., Gruber, Stephen B., Harju, John F., Harrison, Tabitha A., Jacobs, Eric J., Jenkins, Mark A., Jiao, Shuo, Li, Li, Lin, Yi, Manion, Frank J., Moreno, Victor, Mukherjee, Bhramar, Peters, Ulrike, Raskin, Leon, Schumacher, Fredrick R., Seminara, Daniela, Severi, Gianluca, Stenzel, Stephanie L., Thomas, Duncan C., Hopper, John L., Southey, Melissa C., Makalic, Enes, Schmidt, Daniel F., Fletcher, Olivia, Peto, Julian, Gibson, Lorna, dos Santos Silva, Isabel, Hunter, David J., Lindström, Sara, Kraft, Peter, Ahsan, Habib, Whittemore, Alice, Waisfisz, Quinten, Meijers-Heijboer, Hanne, Adank, Muriel, van der Luijt, Rob B., Uitterlinden, Andre G., Hofman, Albert, Meindl, Alfons, Schmutzler, Rita K., Müller-Myhsok, Bertram, Lichtner, Peter, Nevanlinna, Heli, Muranen, Taru A., Aittomäki, Kristiina, Blomqvist, Carl, Chang-Claude, Jenny, Hein, Rebecca, Dahmen, Norbert, Beckman, Lars, Crisponi, Laura, Hall, Per, Czene, Kamila, Irwanto, Astrid, Liu, Jianjun, Easton, Douglas F., Turnbull, Clare, Rahman, Nazneen, Kote-Jarai, Zsofia, Muir, Kenneth, Giles, Graham, Severi, Gianluca, Neal, David, Donovan, Jenny L., Hamdy, Freddie C., Wiklund, Fredrik, Gronberg, Henrik, Haiman, Christopher, Schumacher, Fred, Travis, Ruth, Riboli, Elio, Kraft, Peter, Hunter, David, Gapstur, Susan, Berndt, Sonja, Chanock, Stephen, Han, Younghun, Su, Li, Wei, Yongyue, Hung, Rayjean J., Brhane, Yonathan, McLaughlin, John, Brennan, Paul, McKay, James D., Bickeböller, Heike, Rosenberger, Albert, Houlston, Richard S., Caporaso, Neil, Landi, Maria Teresa, Heinrich, Joachim, Risch, Angela, Wu, Xifeng, Ye, Yuanqing, Christiani, David C., Amos, Christopher I., IGAP Consortium, Colorectal Transdisciplinary Study (CORECT), Discovery, Biology, and Risk of Inherited Variants in Breast Cancer (DRIVE), Elucidating Loci Involved in Prostate Cancer Susceptibility (ELLIPSE), and Transdisciplinary Research in Cancer of the Lung (TRICL)

Published
2017
Full Text
View/download PDF

12. Federated Authentication

Author

Manion, Frank J., Weems, William, McNamee, James, Ochs, Michael F., editor, Casagrande, John T., editor, and Davuluri, Ramana V., editor

Published
2010
Full Text
View/download PDF

18. Quantitative Imaging Assessment for Clinical Trials in Oncology

Author

Hersberger, Katherine E., primary, Mendiratta-Lala, Mishal, additional, Fischer, Rocky, additional, Kaza, Ravi K., additional, Francis, Isaac R., additional, Olszewski, Mirabella S., additional, Harju, John F., additional, Shi, Wei, additional, Manion, Frank J., additional, Al-Hawary, Mahmoud M., additional, and Sahai, Vaibhav, additional

Published
2019
Full Text
View/download PDF

19. Novel Common Genetic Susceptibility Loci for Colorectal Cancer

Author

Schmit, Stephanie L., Edlund, Christopher K., Schumacher, Fredrick R., Gong, Jian, Harrison, Tabitha A., Huyghe, Jeroen R., Qu, Chenxu, Melas, Marilena, Van den Berg, David J., Wang, Hansong, Tring, Stephanie, Plummer, Sarah J., Albanes, Demetrius, Alonso, M. Henar, Amos, Christopher I., Anton, Kristen, Aragaki, Aaron K., Arndt, Volker, Barry, Elizabeth L., Berndt, Sonja I., Bezieau, Stephane, Bien, Stephanie, Bloomer, Amanda, Boehm, Juergen, Boutron-Ruault, Marie-Christine, Brenner, Hermann, Brezina, Stefanie, Buchanan, Daniel D., Butterbach, Katja, Caan, Bette J., Campbell, Peter T., Carlson, Christopher S., Castelao, Jose E., Chan, Andrew T., Chang-Claude, Jenny, Chanock, Stephen J., Cheng, Iona, Cheng, Ya-Wen, Chin, Lee Soo, Church, James M., Church, Timothy, Coetzee, Gerhard A., Cotterchio, Michelle, Correa, Marcia Cruz, Curtis, Keith R., Duggan, David, Easton, Douglas F., English, Dallas, Feskens, Edith J. M., Fischer, Rocky, FitzGerald, Liesel M., Fortini, Barbara K., Fritsche, Lars G., Fuchs, Charles S., Gago-Dominguez, Manuela, Gala, Manish, Gallinger, Steven J., Gauderman, W. James, Giles, Graham G., Giovannucci, Edward L., Gogarten, Stephanie M., Gonzalez-Villalpando, Clicerio, Gonzalez-Villalpando, Elena M., Grady, William M., Greenson, Joel K., Gsur, Andrea, Gunter, Marc, Haiman, Christopher A., Hampe, Jochen, Harlid, Sophia, Harju, John F., Hayes, Richard B., Hofer, Philipp, Hoffmeister, Michael, Hopper, John L., Huang, Shu-Chen, Huerta, Jose Maria, Hudson, Thomas J., Hunter, David J., Idos, Gregory E., Iwasaki, Motoki, Jackson, Rebecca D., Jacobs, Eric J., Jee, Sun Ha, Jenkins, Mark A., Jia, Wei-Hua, Jiao, Shuo, Joshi, Amit D., Kolonel, Laurence N., Kono, Suminori, Kooperberg, Charles, Krogh, Vittorio, Kuehn, Tilman, Kury, Sebastien, LaCroix, Andrea, Laurie, Cecelia A., Lejbkowicz, Flavio, Lemire, Mathieu, Lenz, Heinz-Josef, Levine, David, Li, Christopher I., Li, Li, Lieb, Wolfgang, Lin, Yi, Lindor, Noralane M., Liu, Yun-Ru, Loupakis, Fotios, Lu, Yingchang, Luh, Frank, Ma, Jing, Mancao, Christoph, Manion, Frank J., Markowitz, Sanford D., Martin, Vicente, Matsuda, Koichi, Matsuo, Keitaro, McDonnell, Kevin J., McNeil, Caroline E., Milne, Roger, Molina, Antonio J., Mukherjee, Bhramar, Murphy, Neil, Newcomb, Polly A., Offit, Kenneth, Omichessan, Hanane, Palli, Domenico, Cotore, Jesus P. Paredes, Perez-Mayoral, Julyann, Pharoah, Paul D., Potter, John D., Qu, Conghui, Raskin, Leon, Rennert, Gad, Rennert, Hedy S., Riggs, Bridget M., Schafmayer, Clemens, Schoen, Robert E., Sellers, Thomas A., Seminara, Daniela, Severi, Gianluca, Shi, Wei, Shibata, David, Shu, Xiao-Ou, Siegel, Erin M., Slattery, Martha L., Southey, Melissa, Stadler, Zsofia K., Stern, Mariana C., Stintzing, Sebastian, Taverna, Darin, Thibodeau, Stephen N., Thomas, Duncan C., Trichopoulou, Antonia, Tsugane, Shoichiro, Ulrich, Cornelia M., van Duijnhoven, Franzel J. B., van Guelpen, Bethany, Vijai, Joseph, Virtamo, Jarmo, Weinstein, Stephanie J., White, Emily, Win, Aung Ko, Wolk, Alicja, Woods, Michael, Wu, Anna H., Wu, Kana, Xiang, Yong-Bing, Yen, Yun, Zanke, Brent W., Zeng, Yi-Xin, Zhang, Ben, Zubair, Niha, Kweon, Sun-Seog, Figueiredo, Jane C., Zheng, Wei, Le Marchand, Loic, Lindblom, Annika, Moreno, Victor, Peters, Ulrike, Casey, Graham, Hsu, Li, Conti, David V., Gruber, Stephen B., Schmit, Stephanie L., Edlund, Christopher K., Schumacher, Fredrick R., Gong, Jian, Harrison, Tabitha A., Huyghe, Jeroen R., Qu, Chenxu, Melas, Marilena, Van den Berg, David J., Wang, Hansong, Tring, Stephanie, Plummer, Sarah J., Albanes, Demetrius, Alonso, M. Henar, Amos, Christopher I., Anton, Kristen, Aragaki, Aaron K., Arndt, Volker, Barry, Elizabeth L., Berndt, Sonja I., Bezieau, Stephane, Bien, Stephanie, Bloomer, Amanda, Boehm, Juergen, Boutron-Ruault, Marie-Christine, Brenner, Hermann, Brezina, Stefanie, Buchanan, Daniel D., Butterbach, Katja, Caan, Bette J., Campbell, Peter T., Carlson, Christopher S., Castelao, Jose E., Chan, Andrew T., Chang-Claude, Jenny, Chanock, Stephen J., Cheng, Iona, Cheng, Ya-Wen, Chin, Lee Soo, Church, James M., Church, Timothy, Coetzee, Gerhard A., Cotterchio, Michelle, Correa, Marcia Cruz, Curtis, Keith R., Duggan, David, Easton, Douglas F., English, Dallas, Feskens, Edith J. M., Fischer, Rocky, FitzGerald, Liesel M., Fortini, Barbara K., Fritsche, Lars G., Fuchs, Charles S., Gago-Dominguez, Manuela, Gala, Manish, Gallinger, Steven J., Gauderman, W. James, Giles, Graham G., Giovannucci, Edward L., Gogarten, Stephanie M., Gonzalez-Villalpando, Clicerio, Gonzalez-Villalpando, Elena M., Grady, William M., Greenson, Joel K., Gsur, Andrea, Gunter, Marc, Haiman, Christopher A., Hampe, Jochen, Harlid, Sophia, Harju, John F., Hayes, Richard B., Hofer, Philipp, Hoffmeister, Michael, Hopper, John L., Huang, Shu-Chen, Huerta, Jose Maria, Hudson, Thomas J., Hunter, David J., Idos, Gregory E., Iwasaki, Motoki, Jackson, Rebecca D., Jacobs, Eric J., Jee, Sun Ha, Jenkins, Mark A., Jia, Wei-Hua, Jiao, Shuo, Joshi, Amit D., Kolonel, Laurence N., Kono, Suminori, Kooperberg, Charles, Krogh, Vittorio, Kuehn, Tilman, Kury, Sebastien, LaCroix, Andrea, Laurie, Cecelia A., Lejbkowicz, Flavio, Lemire, Mathieu, Lenz, Heinz-Josef, Levine, David, Li, Christopher I., Li, Li, Lieb, Wolfgang, Lin, Yi, Lindor, Noralane M., Liu, Yun-Ru, Loupakis, Fotios, Lu, Yingchang, Luh, Frank, Ma, Jing, Mancao, Christoph, Manion, Frank J., Markowitz, Sanford D., Martin, Vicente, Matsuda, Koichi, Matsuo, Keitaro, McDonnell, Kevin J., McNeil, Caroline E., Milne, Roger, Molina, Antonio J., Mukherjee, Bhramar, Murphy, Neil, Newcomb, Polly A., Offit, Kenneth, Omichessan, Hanane, Palli, Domenico, Cotore, Jesus P. Paredes, Perez-Mayoral, Julyann, Pharoah, Paul D., Potter, John D., Qu, Conghui, Raskin, Leon, Rennert, Gad, Rennert, Hedy S., Riggs, Bridget M., Schafmayer, Clemens, Schoen, Robert E., Sellers, Thomas A., Seminara, Daniela, Severi, Gianluca, Shi, Wei, Shibata, David, Shu, Xiao-Ou, Siegel, Erin M., Slattery, Martha L., Southey, Melissa, Stadler, Zsofia K., Stern, Mariana C., Stintzing, Sebastian, Taverna, Darin, Thibodeau, Stephen N., Thomas, Duncan C., Trichopoulou, Antonia, Tsugane, Shoichiro, Ulrich, Cornelia M., van Duijnhoven, Franzel J. B., van Guelpen, Bethany, Vijai, Joseph, Virtamo, Jarmo, Weinstein, Stephanie J., White, Emily, Win, Aung Ko, Wolk, Alicja, Woods, Michael, Wu, Anna H., Wu, Kana, Xiang, Yong-Bing, Yen, Yun, Zanke, Brent W., Zeng, Yi-Xin, Zhang, Ben, Zubair, Niha, Kweon, Sun-Seog, Figueiredo, Jane C., Zheng, Wei, Le Marchand, Loic, Lindblom, Annika, Moreno, Victor, Peters, Ulrike, Casey, Graham, Hsu, Li, Conti, David V., and Gruber, Stephen B.

Abstract

Background: Previous genome-wide association studies (GWAS) have identified 42 loci (P < 5x10(-8)) associated with risk of colorectal cancer (CRC). Expanded consortium efforts facilitating the discovery of additional susceptibility loci may capture unexplained familial risk. Methods: We conducted a GWAS in European descent CRC cases and control subjects using a discovery-replication design, followed by examination of novel findings in a multiethnic sample (cumulative n = 163 315). In the discovery stage (36 948 case subjects/30 864 control subjects), we identified genetic variants with a minor allele frequency of 1% or greater associated with risk of CRC using logistic regression followed by a fixed-effects inverse variance weighted meta-analysis. All novel independent variants reaching genome-wide statistical significance (two-sided P < 5x10(-8)) were tested for replication in separate European ancestry samples (12 952 case subjects/48 383 control subjects). Next, we examined the generalizability of discovered variants in East Asians, African Americans, and Hispanics (12 085 case subjects/22 083 control subjects). Finally, we examined the contributions of novel risk variants to familial relative risk and examined the prediction capabilities of a polygenic risk score. All statistical tests were two-sided. Results: The discovery GWAS identified 11 variants associated with CRC at P < 5x10(-8), of which nine (at 4q22.2/5p15.33/5p13.1/6p21.31/6p12.1/10q11.23/12q24.21/16q24.1/20q13.13) independently replicated at a P value of less than .05. Multiethnic follow-up supported the generalizability of discovery findings. These results demonstrated a 14.7% increase in familial relative risk explained by common risk alleles from 10.3% (95% confidence interval [CI] = 7.9% to 13.7%; known variants) to 11.9% (95% CI = 9.2% to 15.5%; known and novel variants). A polygenic risk score identified 4.3% of the population at an odds ratio for developing CRC of at least 2.0. Concl

Published
2019
Full Text
View/download PDF

22. FuGEFlow: data model and markup language for flow cytometry

Author

Manion Frank J, Jones Andrew R, Gasparetto Maura, Wilkinson Peter, Spidlen Josef, Tchuvatkina Olga, Qian Yu, Scheuermann Richard H, Sekaly Rafick-Pierre, and Brinkman Ryan R

Subjects
Computer applications to medicine. Medical informatics, R858-859.7, Biology (General), QH301-705.5
Abstract

Abstract Background Flow cytometry technology is widely used in both health care and research. The rapid expansion of flow cytometry applications has outpaced the development of data storage and analysis tools. Collaborative efforts being taken to eliminate this gap include building common vocabularies and ontologies, designing generic data models, and defining data exchange formats. The Minimum Information about a Flow Cytometry Experiment (MIFlowCyt) standard was recently adopted by the International Society for Advancement of Cytometry. This standard guides researchers on the information that should be included in peer reviewed publications, but it is insufficient for data exchange and integration between computational systems. The Functional Genomics Experiment (FuGE) formalizes common aspects of comprehensive and high throughput experiments across different biological technologies. We have extended FuGE object model to accommodate flow cytometry data and metadata. Methods We used the MagicDraw modelling tool to design a UML model (Flow-OM) according to the FuGE extension guidelines and the AndroMDA toolkit to transform the model to a markup language (Flow-ML). We mapped each MIFlowCyt term to either an existing FuGE class or to a new FuGEFlow class. The development environment was validated by comparing the official FuGE XSD to the schema we generated from the FuGE object model using our configuration. After the Flow-OM model was completed, the final version of the Flow-ML was generated and validated against an example MIFlowCyt compliant experiment description. Results The extension of FuGE for flow cytometry has resulted in a generic FuGE-compliant data model (FuGEFlow), which accommodates and links together all information required by MIFlowCyt. The FuGEFlow model can be used to build software and databases using FuGE software toolkits to facilitate automated exchange and manipulation of potentially large flow cytometry experimental data sets. Additional project documentation, including reusable design patterns and a guide for setting up a development environment, was contributed back to the FuGE project. Conclusion We have shown that an extension of FuGE can be used to transform minimum information requirements in natural language to markup language in XML. Extending FuGE required significant effort, but in our experiences the benefits outweighed the costs. The FuGEFlow is expected to play a central role in describing flow cytometry experiments and ultimately facilitating data exchange including public flow cytometry repositories currently under development.

Published
2009
Full Text
View/download PDF

23. Security and privacy requirements for a multi-institutional cancer research data grid: an interview-based study

Author

Weems William A, Robbins Robert J, Manion Frank J, and Crowley Rebecca S

Subjects
Computer applications to medicine. Medical informatics, R858-859.7
Abstract

Abstract Background Data protection is important for all information systems that deal with human-subjects data. Grid-based systems – such as the cancer Biomedical Informatics Grid (caBIG) – seek to develop new mechanisms to facilitate real-time federation of cancer-relevant data sources, including sources protected under a variety of regulatory laws, such as HIPAA and 21CFR11. These systems embody new models for data sharing, and hence pose new challenges to the regulatory community, and to those who would develop or adopt them. These challenges must be understood by both systems developers and system adopters. In this paper, we describe our work collecting policy statements, expectations, and requirements from regulatory decision makers at academic cancer centers in the United States. We use these statements to examine fundamental assumptions regarding data sharing using data federations and grid computing. Methods An interview-based study of key stakeholders from a sample of US cancer centers. Interviews were structured, and used an instrument that was developed for the purpose of this study. The instrument included a set of problem scenarios – difficult policy situations that were derived during a full-day discussion of potentially problematic issues by a set of project participants with diverse expertise. Each problem scenario included a set of open-ended questions that were designed to elucidate stakeholder opinions and concerns. Interviews were transcribed verbatim and used for both qualitative and quantitative analysis. For quantitative analysis, data was aggregated at the individual or institutional unit of analysis, depending on the specific interview question. Results Thirty-one (31) individuals at six cancer centers were contacted to participate. Twenty-four out of thirty-one (24/31) individuals responded to our request- yielding a total response rate of 77%. Respondents included IRB directors and policy-makers, privacy and security officers, directors of offices of research, information security officers and university legal counsel. Nineteen total interviews were conducted over a period of 16 weeks. Respondents provided answers for all four scenarios (a total of 87 questions). Results were grouped by broad themes, including among others: governance, legal and financial issues, partnership agreements, de-identification, institutional technical infrastructure for security and privacy protection, training, risk management, auditing, IRB issues, and patient/subject consent. Conclusion The findings suggest that with additional work, large scale federated sharing of data within a regulated environment is possible. A key challenge is developing suitable models for authentication and authorization practices within a federated environment. Authentication – the recognition and validation of a person's identity – is in fact a global property of such systems, while authorization – the permission to access data or resources – mimics data sharing agreements in being best served at a local level. Nine specific recommendations result from the work and are discussed in detail. These include: (1) the necessity to construct separate legal or corporate entities for governance of federated sharing initiatives on this scale; (2) consensus on the treatment of foreign and commercial partnerships; (3) the development of risk models and risk management processes; (4) development of technical infrastructure to support the credentialing process associated with research including human subjects; (5) exploring the feasibility of developing large-scale, federated honest broker approaches; (6) the development of suitable, federated identity provisioning processes to support federated authentication and authorization; (7) community development of requisite HIPAA and research ethics training modules by federation members; (8) the recognition of the need for central auditing requirements and authority, and; (9) use of two-protocol data exchange models where possible in the federation.

Published
2009
Full Text
View/download PDF

24. Novel Common Genetic Susceptibility Loci for Colorectal Cancer.

Author

Schmit, Stephanie L, Edlund, Christopher K, Schumacher, Fredrick R, Gong, Jian, Harrison, Tabitha A, Huyghe, Jeroen R, Qu, Chenxu, Melas, Marilena, Van Den Berg, David J, Wang, Hansong, Tring, Stephanie, Plummer, Sarah J, Albanes, Demetrius, Alonso, M Henar, Amos, Christopher I, Anton, Kristen, Aragaki, Aaron K, Arndt, Volker, Barry, Elizabeth L, Berndt, Sonja I, Bezieau, Stéphane, Bien, Stephanie, Bloomer, Amanda, Boehm, Juergen, Boutron-Ruault, Marie-Christine, Brenner, Hermann, Brezina, Stefanie, Buchanan, Daniel D, Butterbach, Katja, Caan, Bette J, Campbell, Peter T, Carlson, Christopher S, Castelao, Jose E, Chan, Andrew T, Chang-Claude, Jenny, Chanock, Stephen J, Cheng, Iona, Cheng, Ya-Wen, Chin, Lee Soo, Church, James M, Church, Timothy, Coetzee, Gerhard A, Cotterchio, Michelle, Cruz Correa, Marcia, Curtis, Keith R, Duggan, David, Easton, Douglas F, English, Dallas, Feskens, Edith J M, Fischer, Rocky, FitzGerald, Liesel M, Fortini, Barbara K, Fritsche, Lars G, Fuchs, Charles S, Gago-Dominguez, Manuela, Gala, Manish, Gallinger, Steven J, Gauderman, W James, Giles, Graham G, Giovannucci, Edward L, Gogarten, Stephanie M, Gonzalez-Villalpando, Clicerio, Gonzalez-Villalpando, Elena M, Grady, William M, Greenson, Joel K, Gsur, Andrea, Gunter, Marc, Haiman, Christopher A, Hampe, Jochen, Harlid, Sophia, Harju, John F, Hayes, Richard B, Hofer, Philipp, Hoffmeister, Michael, Hopper, John L, Huang, Shu-Chen, Huerta, Jose Maria, Hudson, Thomas J, Hunter, David J, Idos, Gregory E, Iwasaki, Motoki, Jackson, Rebecca D, Jacobs, Eric J, Jee, Sun Ha, Jenkins, Mark A, Jia, Wei-Hua, Jiao, Shuo, Joshi, Amit D, Kolonel, Laurence N, Kono, Suminori, Kooperberg, Charles, Krogh, Vittorio, Kuehn, Tilman, Küry, Sébastien, LaCroix, Andrea, Laurie, Cecelia A, Lejbkowicz, Flavio, Lemire, Mathieu, Lenz, Heinz-Josef, Levine, David, Li, Christopher I, Li, Li, Lieb, Wolfgang, Lin, Yi, Lindor, Noralane M, Liu, Yun-Ru, Loupakis, Fotios, Lu, Yingchang, Luh, Frank, Ma, Jing, Mancao, Christoph, Manion, Frank J, Markowitz, Sanford D, Martin, Vicente, Matsuda, Koichi, Matsuo, Keitaro, McDonnell, Kevin J, McNeil, Caroline E, Milne, Roger, Molina, Antonio J, Mukherjee, Bhramar, Murphy, Neil, Newcomb, Polly A, Offit, Kenneth, Omichessan, Hanane, Palli, Domenico, Cotoré, Jesus P Paredes, Pérez-Mayoral, Julyann, Pharoah, Paul D, Potter, John D, Qu, Conghui, Raskin, Leon, Rennert, Gad, Rennert, Hedy S, Riggs, Bridget M, Schafmayer, Clemens, Schoen, Robert E, Sellers, Thomas A, Seminara, Daniela, Severi, Gianluca, Shi, Wei, Shibata, David, Shu, Xiao-Ou, Siegel, Erin M, Slattery, Martha L, Southey, Melissa, Stadler, Zsofia K, Stern, Mariana C, Stintzing, Sebastian, Taverna, Darin, Thibodeau, Stephen N, Thomas, Duncan C, Trichopoulou, Antonia, Tsugane, Shoichiro, Ulrich, Cornelia M, van Duijnhoven, Franzel J B, van Guelpan, Bethany, Vijai, Joseph, Virtamo, Jarmo, Weinstein, Stephanie J, White, Emily, Win, Aung Ko, Wolk, Alicja, Woods, Michael, Wu, Anna H, Wu, Kana, Xiang, Yong-Bing, Yen, Yun, Zanke, Brent W, Zeng, Yi-Xin, Zhang, Ben, Zubair, Niha, Kweon, Sun-Seog, Figueiredo, Jane C, Zheng, Wei, Marchand, Loic Le, Lindblom, Annika, Moreno, Victor, Peters, Ulrike, Casey, Graham, Hsu, Li, Conti, David V, Gruber, Stephen B, Schmit, Stephanie L, Edlund, Christopher K, Schumacher, Fredrick R, Gong, Jian, Harrison, Tabitha A, Huyghe, Jeroen R, Qu, Chenxu, Melas, Marilena, Van Den Berg, David J, Wang, Hansong, Tring, Stephanie, Plummer, Sarah J, Albanes, Demetrius, Alonso, M Henar, Amos, Christopher I, Anton, Kristen, Aragaki, Aaron K, Arndt, Volker, Barry, Elizabeth L, Berndt, Sonja I, Bezieau, Stéphane, Bien, Stephanie, Bloomer, Amanda, Boehm, Juergen, Boutron-Ruault, Marie-Christine, Brenner, Hermann, Brezina, Stefanie, Buchanan, Daniel D, Butterbach, Katja, Caan, Bette J, Campbell, Peter T, Carlson, Christopher S, Castelao, Jose E, Chan, Andrew T, Chang-Claude, Jenny, Chanock, Stephen J, Cheng, Iona, Cheng, Ya-Wen, Chin, Lee Soo, Church, James M, Church, Timothy, Coetzee, Gerhard A, Cotterchio, Michelle, Cruz Correa, Marcia, Curtis, Keith R, Duggan, David, Easton, Douglas F, English, Dallas, Feskens, Edith J M, Fischer, Rocky, FitzGerald, Liesel M, Fortini, Barbara K, Fritsche, Lars G, Fuchs, Charles S, Gago-Dominguez, Manuela, Gala, Manish, Gallinger, Steven J, Gauderman, W James, Giles, Graham G, Giovannucci, Edward L, Gogarten, Stephanie M, Gonzalez-Villalpando, Clicerio, Gonzalez-Villalpando, Elena M, Grady, William M, Greenson, Joel K, Gsur, Andrea, Gunter, Marc, Haiman, Christopher A, Hampe, Jochen, Harlid, Sophia, Harju, John F, Hayes, Richard B, Hofer, Philipp, Hoffmeister, Michael, Hopper, John L, Huang, Shu-Chen, Huerta, Jose Maria, Hudson, Thomas J, Hunter, David J, Idos, Gregory E, Iwasaki, Motoki, Jackson, Rebecca D, Jacobs, Eric J, Jee, Sun Ha, Jenkins, Mark A, Jia, Wei-Hua, Jiao, Shuo, Joshi, Amit D, Kolonel, Laurence N, Kono, Suminori, Kooperberg, Charles, Krogh, Vittorio, Kuehn, Tilman, Küry, Sébastien, LaCroix, Andrea, Laurie, Cecelia A, Lejbkowicz, Flavio, Lemire, Mathieu, Lenz, Heinz-Josef, Levine, David, Li, Christopher I, Li, Li, Lieb, Wolfgang, Lin, Yi, Lindor, Noralane M, Liu, Yun-Ru, Loupakis, Fotios, Lu, Yingchang, Luh, Frank, Ma, Jing, Mancao, Christoph, Manion, Frank J, Markowitz, Sanford D, Martin, Vicente, Matsuda, Koichi, Matsuo, Keitaro, McDonnell, Kevin J, McNeil, Caroline E, Milne, Roger, Molina, Antonio J, Mukherjee, Bhramar, Murphy, Neil, Newcomb, Polly A, Offit, Kenneth, Omichessan, Hanane, Palli, Domenico, Cotoré, Jesus P Paredes, Pérez-Mayoral, Julyann, Pharoah, Paul D, Potter, John D, Qu, Conghui, Raskin, Leon, Rennert, Gad, Rennert, Hedy S, Riggs, Bridget M, Schafmayer, Clemens, Schoen, Robert E, Sellers, Thomas A, Seminara, Daniela, Severi, Gianluca, Shi, Wei, Shibata, David, Shu, Xiao-Ou, Siegel, Erin M, Slattery, Martha L, Southey, Melissa, Stadler, Zsofia K, Stern, Mariana C, Stintzing, Sebastian, Taverna, Darin, Thibodeau, Stephen N, Thomas, Duncan C, Trichopoulou, Antonia, Tsugane, Shoichiro, Ulrich, Cornelia M, van Duijnhoven, Franzel J B, van Guelpan, Bethany, Vijai, Joseph, Virtamo, Jarmo, Weinstein, Stephanie J, White, Emily, Win, Aung Ko, Wolk, Alicja, Woods, Michael, Wu, Anna H, Wu, Kana, Xiang, Yong-Bing, Yen, Yun, Zanke, Brent W, Zeng, Yi-Xin, Zhang, Ben, Zubair, Niha, Kweon, Sun-Seog, Figueiredo, Jane C, Zheng, Wei, Marchand, Loic Le, Lindblom, Annika, Moreno, Victor, Peters, Ulrike, Casey, Graham, Hsu, Li, Conti, David V, and Gruber, Stephen B

Abstract

Background: Previous genome-wide association studies (GWAS) have identified 42 loci (P < 5 × 10-8) associated with risk of colorectal cancer (CRC). Expanded consortium efforts facilitating the discovery of additional susceptibility loci may capture unexplained familial risk. Methods: We conducted a GWAS in European descent CRC cases and control subjects using a discovery-replication design, followed by examination of novel findings in a multiethnic sample (cumulative n = 163 315). In the discovery stage (36 948 case subjects/30 864 control subjects), we identified genetic variants with a minor allele frequency of 1% or greater associated with risk of CRC using logistic regression followed by a fixed-effects inverse variance weighted meta-analysis. All novel independent variants reaching genome-wide statistical significance (two-sided P < 5 × 10-8) were tested for replication in separate European ancestry samples (12 952 case subjects/48 383 control subjects). Next, we examined the generalizability of discovered variants in East Asians, African Americans, and Hispanics (12 085 case subjects/22 083 control subjects). Finally, we examined the contributions of novel risk variants to familial relative risk and examined the prediction capabilities of a polygenic risk score. All statistical tests were two-sided. Results: The discovery GWAS identified 11 variants associated with CRC at P < 5 × 10-8, of which nine (at 4q22.2/5p15.33/5p13.1/6p21.31/6p12.1/10q11.23/12q24.21/16q24.1/20q13.13) independently replicated at a P value of less than .05. Multiethnic follow-up supported the generalizability of discovery findings. These results demonstrated a 14.7% increase in familial relative risk explained by common risk alleles from 10.3% (95% confidence interval [CI] = 7.9% to 13.7%; known variants) to 11.9% (95% CI = 9.2% to 15.5%; known and novel variants). A polygenic risk score identified 4.3% of the population at an odds ratio for developing CRC of at least 2.0. Concl

Published
2018
Full Text
View/download PDF

25. Investigating the genetic relationship between Alzheimer’s disease and cancer using GWAS summary statistics

Author

Feng, Yen Chen Anne, Cho, Kelly, Lindstrom, Sara, Kraft, Peter, Cormack, Jean, Blalock, Kendra, Campbell, Peter T., Casey, Graham, Conti, David V., Edlund, Christopher K., Figueiredo, Jane, James Gauderman, W., Gong, Jian, Green, Roger C., Gruber, Stephen B., Harju, John F., Harrison, Tabitha A., Jacobs, Eric J, Jenkins, Mark A., Jiao, Shuo, Li, Li, Lin, Yi, Manion, Frank J., Moreno, Victor, Mukherjee, Bhramar, Peters, Ulrike, Raskin, Leon, Schumacher, Fredrick R., Seminara, Daniela, Severi, Gianluca, Stenzel, Stephanie L., Thomas, Duncan C., Hopper, John L., Southey, Melissa C., Makalic, Enes, Schmidt, Daniel F., Fletcher, Olivia, Peto, Julian, Gibson, Lorna, Dos-Santos-Silva, Isabel, Hunter, David J., Lindström, Sara, Ahsan, Habib, Whittemore, Alice S., Waisfisz, Quinten, Meijers-Heijboer, Hanne, Adank, Muriel A., van der Luijt, Rob B., Uitterlinden, Andre G, IGAP Consortium, Colorectal Transdisciplinary Study (CORECT), Discovery, Biology, and Risk of Inherited Variants in Breast Cancer (DRIVE), Elucidating Loci Involved in Prostate Cancer Susceptibility (ELLIPSE), and Transdisciplinary Research in Cancer of the Lung (TRICL)

Subjects
Genetics, Genetics(clinical)
Abstract

Growing evidence from both epidemiology and basic science suggest an inverse association between Alzheimer’s disease (AD) and cancer. We examined the genetic relationship between AD and various cancer types using GWAS summary statistics from the IGAP and GAME-ON consortia. Sample size ranged from 9931 to 54,162; SNPs were imputed to the 1000 Genomes European panel. Our results based on cross-trait LD Score regression showed a significant positive genetic correlation between AD and five cancers combined (colon, breast, prostate, ovarian, lung; rg = 0.17, P = 0.04), and specifically with breast cancer (ER-negative and overall; rg = 0.21 and 0.18, P = 0.035 and 0.034) and lung cancer (adenocarcinoma, squamous cell carcinoma and overall; rg = 0.31, 0.38 and 0.30, P = 0.029, 0.016, and 0.006). Estimating the genetic correlation in specific functional categories revealed mixed positive and negative signals, notably stronger at annotations associated with increased enhancer activity. This suggests a role of gene expression regulators in the shared genetic etiology between AD and cancer, and that some shared variants modulate disease risk concordantly while others have effects in opposite directions. Due to power issues, we did not detect cross-phenotype associations at individual SNPs. This genetic overlap is not likely driven by a handful of major loci. Our study is the first to examine the co-heritability of AD and cancer leveraging large-scale GWAS results. The functional categories highlighted in this study need further investigation to illustrate the details of the genetic sharing and to bridge between different levels of associations.

Published
2017

26. Novel Common Genetic Susceptibility Loci for Colorectal Cancer

Author

Schmit, Stephanie L, primary, Edlund, Christopher K, additional, Schumacher, Fredrick R, additional, Gong, Jian, additional, Harrison, Tabitha A, additional, Huyghe, Jeroen R, additional, Qu, Chenxu, additional, Melas, Marilena, additional, Van Den Berg, David J, additional, Wang, Hansong, additional, Tring, Stephanie, additional, Plummer, Sarah J, additional, Albanes, Demetrius, additional, Alonso, M Henar, additional, Amos, Christopher I, additional, Anton, Kristen, additional, Aragaki, Aaron K, additional, Arndt, Volker, additional, Barry, Elizabeth L, additional, Berndt, Sonja I, additional, Bezieau, Stéphane, additional, Bien, Stephanie, additional, Bloomer, Amanda, additional, Boehm, Juergen, additional, Boutron-Ruault, Marie-Christine, additional, Brenner, Hermann, additional, Brezina, Stefanie, additional, Buchanan, Daniel D, additional, Butterbach, Katja, additional, Caan, Bette J, additional, Campbell, Peter T, additional, Carlson, Christopher S, additional, Castelao, Jose E, additional, Chan, Andrew T, additional, Chang-Claude, Jenny, additional, Chanock, Stephen J, additional, Cheng, Iona, additional, Cheng, Ya-Wen, additional, Chin, Lee Soo, additional, Church, James M, additional, Church, Timothy, additional, Coetzee, Gerhard A, additional, Cotterchio, Michelle, additional, Cruz Correa, Marcia, additional, Curtis, Keith R, additional, Duggan, David, additional, Easton, Douglas F, additional, English, Dallas, additional, Feskens, Edith J M, additional, Fischer, Rocky, additional, FitzGerald, Liesel M, additional, Fortini, Barbara K, additional, Fritsche, Lars G, additional, Fuchs, Charles S, additional, Gago-Dominguez, Manuela, additional, Gala, Manish, additional, Gallinger, Steven J, additional, Gauderman, W James, additional, Giles, Graham G, additional, Giovannucci, Edward L, additional, Gogarten, Stephanie M, additional, Gonzalez-Villalpando, Clicerio, additional, Gonzalez-Villalpando, Elena M, additional, Grady, William M, additional, Greenson, Joel K, additional, Gsur, Andrea, additional, Gunter, Marc, additional, Haiman, Christopher A, additional, Hampe, Jochen, additional, Harlid, Sophia, additional, Harju, John F, additional, Hayes, Richard B, additional, Hofer, Philipp, additional, Hoffmeister, Michael, additional, Hopper, John L, additional, Huang, Shu-Chen, additional, Huerta, Jose Maria, additional, Hudson, Thomas J, additional, Hunter, David J, additional, Idos, Gregory E, additional, Iwasaki, Motoki, additional, Jackson, Rebecca D, additional, Jacobs, Eric J, additional, Jee, Sun Ha, additional, Jenkins, Mark A, additional, Jia, Wei-Hua, additional, Jiao, Shuo, additional, Joshi, Amit D, additional, Kolonel, Laurence N, additional, Kono, Suminori, additional, Kooperberg, Charles, additional, Krogh, Vittorio, additional, Kuehn, Tilman, additional, Küry, Sébastien, additional, LaCroix, Andrea, additional, Laurie, Cecelia A, additional, Lejbkowicz, Flavio, additional, Lemire, Mathieu, additional, Lenz, Heinz-Josef, additional, Levine, David, additional, Li, Christopher I, additional, Li, Li, additional, Lieb, Wolfgang, additional, Lin, Yi, additional, Lindor, Noralane M, additional, Liu, Yun-Ru, additional, Loupakis, Fotios, additional, Lu, Yingchang, additional, Luh, Frank, additional, Ma, Jing, additional, Mancao, Christoph, additional, Manion, Frank J, additional, Markowitz, Sanford D, additional, Martin, Vicente, additional, Matsuda, Koichi, additional, Matsuo, Keitaro, additional, McDonnell, Kevin J, additional, McNeil, Caroline E, additional, Milne, Roger, additional, Molina, Antonio J, additional, Mukherjee, Bhramar, additional, Murphy, Neil, additional, Newcomb, Polly A, additional, Offit, Kenneth, additional, Omichessan, Hanane, additional, Palli, Domenico, additional, Cotoré, Jesus P Paredes, additional, Pérez-Mayoral, Julyann, additional, Pharoah, Paul D, additional, Potter, John D, additional, Qu, Conghui, additional, Raskin, Leon, additional, Rennert, Gad, additional, Rennert, Hedy S, additional, Riggs, Bridget M, additional, Schafmayer, Clemens, additional, Schoen, Robert E, additional, Sellers, Thomas A, additional, Seminara, Daniela, additional, Severi, Gianluca, additional, Shi, Wei, additional, Shibata, David, additional, Shu, Xiao-Ou, additional, Siegel, Erin M, additional, Slattery, Martha L, additional, Southey, Melissa, additional, Stadler, Zsofia K, additional, Stern, Mariana C, additional, Stintzing, Sebastian, additional, Taverna, Darin, additional, Thibodeau, Stephen N, additional, Thomas, Duncan C, additional, Trichopoulou, Antonia, additional, Tsugane, Shoichiro, additional, Ulrich, Cornelia M, additional, van Duijnhoven, Franzel J B, additional, van Guelpan, Bethany, additional, Vijai, Joseph, additional, Virtamo, Jarmo, additional, Weinstein, Stephanie J, additional, White, Emily, additional, Win, Aung Ko, additional, Wolk, Alicja, additional, Woods, Michael, additional, Wu, Anna H, additional, Wu, Kana, additional, Xiang, Yong-Bing, additional, Yen, Yun, additional, Zanke, Brent W, additional, Zeng, Yi-Xin, additional, Zhang, Ben, additional, Zubair, Niha, additional, Kweon, Sun-Seog, additional, Figueiredo, Jane C, additional, Zheng, Wei, additional, Marchand, Loic Le, additional, Lindblom, Annika, additional, Moreno, Victor, additional, Peters, Ulrike, additional, Casey, Graham, additional, Hsu, Li, additional, Conti, David V, additional, and Gruber, Stephen B, additional

Published
2018
Full Text
View/download PDF

27. Investigating the genetic relationship between Alzheimer’s disease and cancer using GWAS summary statistics

Author

Genetica Sectie Genoomdiagnostiek, Cancer, Feng, Yen Chen Anne, Cho, Kelly, Lindstrom, Sara, Kraft, Peter, Cormack, Jean, Blalock, Kendra, Campbell, Peter T., Casey, Graham, Conti, David V., Edlund, Christopher K., Figueiredo, Jane, James Gauderman, W., Gong, Jian, Green, Roger C., Gruber, Stephen B., Harju, John F., Harrison, Tabitha A., Jacobs, Eric J, Jenkins, Mark A., Jiao, Shuo, Li, Li, Lin, Yi, Manion, Frank J., Moreno, Victor, Mukherjee, Bhramar, Peters, Ulrike, Raskin, Leon, Schumacher, Fredrick R., Seminara, Daniela, Severi, Gianluca, Stenzel, Stephanie L., Thomas, Duncan C., Hopper, John L., Southey, Melissa C., Makalic, Enes, Schmidt, Daniel F., Fletcher, Olivia, Peto, Julian, Gibson, Lorna, Dos-Santos-Silva, Isabel, Hunter, David J., Lindström, Sara, Ahsan, Habib, Whittemore, Alice S., Waisfisz, Quinten, Meijers-Heijboer, Hanne, Adank, Muriel A., van der Luijt, Rob B., Uitterlinden, Andre G, IGAP Consortium, Colorectal Transdisciplinary Study (CORECT), Discovery, Biology, and Risk of Inherited Variants in Breast Cancer (DRIVE), Elucidating Loci Involved in Prostate Cancer Susceptibility (ELLIPSE), Transdisciplinary Research in Cancer of the Lung (TRICL), Genetica Sectie Genoomdiagnostiek, Cancer, Feng, Yen Chen Anne, Cho, Kelly, Lindstrom, Sara, Kraft, Peter, Cormack, Jean, Blalock, Kendra, Campbell, Peter T., Casey, Graham, Conti, David V., Edlund, Christopher K., Figueiredo, Jane, James Gauderman, W., Gong, Jian, Green, Roger C., Gruber, Stephen B., Harju, John F., Harrison, Tabitha A., Jacobs, Eric J, Jenkins, Mark A., Jiao, Shuo, Li, Li, Lin, Yi, Manion, Frank J., Moreno, Victor, Mukherjee, Bhramar, Peters, Ulrike, Raskin, Leon, Schumacher, Fredrick R., Seminara, Daniela, Severi, Gianluca, Stenzel, Stephanie L., Thomas, Duncan C., Hopper, John L., Southey, Melissa C., Makalic, Enes, Schmidt, Daniel F., Fletcher, Olivia, Peto, Julian, Gibson, Lorna, Dos-Santos-Silva, Isabel, Hunter, David J., Lindström, Sara, Ahsan, Habib, Whittemore, Alice S., Waisfisz, Quinten, Meijers-Heijboer, Hanne, Adank, Muriel A., van der Luijt, Rob B., Uitterlinden, Andre G, IGAP Consortium, Colorectal Transdisciplinary Study (CORECT), Discovery, Biology, and Risk of Inherited Variants in Breast Cancer (DRIVE), Elucidating Loci Involved in Prostate Cancer Susceptibility (ELLIPSE), and Transdisciplinary Research in Cancer of the Lung (TRICL)

Published
2017

28. Association between Adult Height and Risk of Colorectal, Lung, and Prostate Cancer:Results from Meta-analyses of Prospective Studies and Mendelian Randomization Analyses

Author

Khankari, Nikhil K., Shu, Xiao Ou, Wen, Wanqing, Kraft, Peter, Lindström, Sara, Peters, Ulrike, Schildkraut, Joellen, Schumacher, Fredrick, Bofetta, Paolo, Risch, Angela, Bickeböller, Heike, Amos, Christopher I., Easton, Douglas, Eeles, Rosalind A., Gruber, Stephen B., Haiman, Christopher A., Hunter, David J., Chanock, Stephen J., Pierce, Brandon L., Zheng, Wei, Blalock, Kendra, Campbell, Peter T., Casey, Graham, Conti, David V., Edlund, Christopher K., Figueiredo, Jane, James Gauderman, W., Gong, Jian, Green, Roger C., Harju, John F., Harrison, Tabitha A., Jacobs, Eric J., Jenkins, Mark A., Jiao, Shuo, Li, Li, Lin, Yi, Manion, Frank J., Moreno, Victor, Mukherjee, Bhramar, Raskin, Leon, Schumacher, Fredrick R., Seminara, Daniela, Severi, Gianluca, Stenzel, Stephanie L., Thomas, Duncan C., Hopper, John L., Southey, Melissa C., Makalic, Enes, Schmidt, Daniel F., Fletcher, Olivia, Peto, Julian, Gibson, Lorna, dos Santos Silva, Isabel, Ahsan, Habib, Whittemore, Alice, Waisfisz, Quinten, Meijers-Heijboer, Hanne, Adank, Muriel, van der Luijt, Rob B., Uitterlinden, Andre G., Hofman, Albert, Meindl, Alfons, Schmutzler, Rita K., Müller-Myhsok, Bertram, Lichtner, Peter, Nevanlinna, Heli, Muranen, Taru A., Aittomäki, Kristiina, Blomqvist, Carl, Chang-Claude, Jenny, Hein, Rebecca, Dahmen, Norbert, Beckman, Lars, Crisponi, Laura, Hall, Per, Czene, Kamila, Irwanto, Astrid, Liu, Jianjun, Easton, Douglas F., Turnbull, Clare, Rahman, Nazneen, Eeles, Rosalind, Kote-Jarai, Zsofia, Muir, Kenneth, Giles, Graham, Neal, David, Donovan, Jenny L., Hamdy, Freddie C., Wiklund, Fredrik, Gronberg, Henrik, Haiman, Christopher, Schumacher, Fred, Travis, Ruth, Riboli, Elio, Hunter, David, Gapstur, Susan, Berndt, Sonja, Chanock, Stephen, Han, Younghun, Su, Li, Wei, Yongyue, Hung, Rayjean J., Brhane, Yonathan, McLaughlin, John, Brennan, Paul, McKay, James D., Rosenberger, Albert, Houlston, Richard S., Caporaso, Neil, Teresa Landi, Maria, Heinrich, Joachim, Wu, Xifeng, Ye, Yuanqing, Christiani, David C., Human genetics, CCA - Evaluation of Cancer Care, Eeles, Rosalind A [0000-0002-7472-5384], and Apollo - University of Cambridge Repository

Subjects
Oncology, Male, Lung Neoplasms, Social Sciences, Genome-wide association study, Biochemistry, 0302 clinical medicine, Sociology, Odds Ratio, Prospective Studies, Aged, 80 and over, Prostate Diseases, 11 Medical And Health Sciences, General Medicine, Genomics, 3. Good health, 030220 oncology & carcinogenesis, Meta-analysis, Physical Sciences, Transdisciplinary Research in Cancer of the Lung (TRICL), Medicine, DIFFERENT ANATOMIC SITES, BODY-MASS-INDEX, Statistics (Mathematics), medicine.medical_specialty, 03 medical and health sciences, Exocrine Glands, SDG 3 - Good Health and Well-being, Genome-Wide Association Studies, Genetics, Humans, Statistical Methods, Molecular Biology, RECTAL-CANCER, Aged, Science & Technology, Biology and Life Sciences, Computational Biology, Genetic Variation, Odds ratio, Mendelian Randomization Analysis, medicine.disease, Genitourinary Tract Tumors, 030104 developmental biology, Relative risk, OLDER WOMEN, Prostate Gland, Mathematics, Meta-Analysis, Elucidating Loci Involved in Prostate Cancer Susceptibility (ELLIPSE), 0301 basic medicine, Bioinformatics, Lung and Intrathoracic Tumors, Mathematical and Statistical Techniques, NETHERLANDS COHORT, Consortia, Risk Factors, GROWTH-FACTOR (IGF)-I, Medicine and Health Sciences, Prospective cohort study, Prostate Cancer, Middle Aged, Research Design, Female, Anatomy, Colorectal Neoplasms, Life Sciences & Biomedicine, NORWEGIAN MEN, Research Article, Biotechnology, Adult, Urology, IGF-BINDING PROTEINS, Research and Analysis Methods, Young Adult, Medicine, General & Internal, Discovery, Biology, and Risk of Inherited Variants in Breast Cancer (DRIVE), General & Internal Medicine, Internal medicine, Mendelian randomization, medicine, Journal Article, Colorectal Transdisciplinary Study (CORECT), Lung cancer, Colorectal Cancer, business.industry, Cancers and Neoplasms, Prostatic Neoplasms, JAPANESE MEN, Human Genetics, Cell Biology, Genome Analysis, Body Height, Prostate cancer, Lung and intrathoracic tumors, Prospective studies, Colorectal cancer, Prostate gland, Genome-wide association studies, FOLLOW-UP, business, Genome-Wide Association Study
Abstract

Background Observational studies examining associations between adult height and risk of colorectal, prostate, and lung cancers have generated mixed results. We conducted meta-analyses using data from prospective cohort studies and further carried out Mendelian randomization analyses, using height-associated genetic variants identified in a genome-wide association study (GWAS), to evaluate the association of adult height with these cancers. Methods and Findings A systematic review of prospective studies was conducted using the PubMed, Embase, and Web of Science databases. Using meta-analyses, results obtained from 62 studies were summarized for the association of a 10-cm increase in height with cancer risk. Mendelian randomization analyses were conducted using summary statistics obtained for 423 genetic variants identified from a recent GWAS of adult height and from a cancer genetics consortium study of multiple cancers that included 47,800 cases and 81,353 controls. For a 10-cm increase in height, the summary relative risks derived from the meta-analyses of prospective studies were 1.12 (95% CI 1.10, 1.15), 1.07 (95% CI 1.05, 1.10), and 1.06 (95% CI 1.02, 1.11) for colorectal, prostate, and lung cancers, respectively. Mendelian randomization analyses showed increased risks of colorectal (odds ratio [OR] = 1.58, 95% CI 1.14, 2.18) and lung cancer (OR = 1.10, 95% CI 1.00, 1.22) associated with each 10-cm increase in genetically predicted height. No association was observed for prostate cancer (OR = 1.03, 95% CI 0.92, 1.15). Our meta-analysis was limited to published studies. The sample size for the Mendelian randomization analysis of colorectal cancer was relatively small, thus affecting the precision of the point estimate. Conclusions Our study provides evidence for a potential causal association of adult height with the risk of colorectal and lung cancers and suggests that certain genetic factors and biological pathways affecting adult height may also affect the risk of these cancers., In a Mendelian randomisation study Pierce and colleagues show a genetic association between adult height and increased risk of colorectal and lung cancer., Author Summary Why Was This Study Done? Several previous observational studies have examined the association between adult height and risk of cancers of the lung, colon/rectum, and prostate; however, it remains unclear whether adult height is indeed related to the risk of these cancers. What Did the Researchers Do and Find? We conducted a systematic review and meta-analysis of prospective cohort studies that examined the association between adult height and the risk of colorectal, lung, and prostate cancers. To overcome inherent limitations of observational study designs, we conducted Mendelian randomization analyses using genetic data generated from a large multi-center consortium study including 47,800 cases and 81,353 controls. In the meta-analysis of the prospective observational studies, we found a 12% increased risk of colorectal cancer, a 7% increased risk of prostate cancer, and a 6% increased risk of lung cancer for every ten-centimeter increase in height, and this increased risk was corroborated in the Mendelian randomization analyses for colorectal (58%) and lung cancer (10%). What Do These Findings Mean? Our study provides strong evidence for an association between adult height and risk of colorectal and lung cancer, and suggests that certain genetic and biological factors that affect height may also affect the risk of these cancers. However, our meta-analysis was limited to published studies, and the sample size for the Mendelian randomization analysis for colorectal cancer was relatively small, affecting the precision of the risk estimate.

Published
2016

29. Association between Adult Height and Risk of Colorectal, Lung, and Prostate Cancer : Results from Meta-analyses of Prospective Studies and Mendelian Randomization Analyses

Author

Khankari, Nikhil K., Shu, Xiao Ou, Wen, Wanqing, Kraft, Peter, Lindström, Sara, Peters, Ulrike, Schildkraut, Joellen, Schumacher, Fredrick, Bofetta, Paolo, Risch, Angela, Bickeböller, Heike, Amos, Christopher I., Easton, Douglas, Eeles, Rosalind A., Gruber, Stephen B., Haiman, Christopher A., Hunter, David J., Chanock, Stephen J., Pierce, Brandon L., Zheng, Wei, Blalock, Kendra, Campbell, Peter T., Casey, Graham, Conti, David V., Edlund, Christopher K., Figueiredo, Jane, James Gauderman, W., Gong, Jian, Green, Roger C., Harju, John F., Harrison, Tabitha A., Jacobs, Eric J., Jenkins, Mark A., Jiao, Shuo, Li, Li, Lin, Yi, Manion, Frank J., Moreno, Victor, Mukherjee, Bhramar, Raskin, Leon, Schumacher, Fredrick R., Seminara, Daniela, Severi, Gianluca, Stenzel, Stephanie L., Thomas, Duncan C., Hopper, John L., Southey, Melissa C., Makalic, Enes, Schmidt, Daniel F., Fletcher, Olivia, Peto, Julian, Gibson, Lorna, dos Santos Silva, Isabel, Ahsan, Habib, Whittemore, Alice, Waisfisz, Quinten, Meijers-Heijboer, Hanne, Adank, Muriel, van der Luijt, Rob B., Uitterlinden, Andre G., Hofman, Albert, Meindl, Alfons, Schmutzler, Rita K., Müller-Myhsok, Bertram, Lichtner, Peter, Nevanlinna, Heli, Muranen, Taru A., Aittomäki, Kristiina, Blomqvist, Carl, Chang-Claude, Jenny, Hein, Rebecca, Dahmen, Norbert, Beckman, Lars, Crisponi, Laura, Hall, Per, Czene, Kamila, Irwanto, Astrid, Liu, Jianjun, Easton, Douglas F., Turnbull, Clare, Rahman, Nazneen, Eeles, Rosalind, Kote-Jarai, Zsofia, Muir, Kenneth, Giles, Graham, Neal, David, Donovan, Jenny L., Hamdy, Freddie C., Wiklund, Fredrik, Gronberg, Henrik, Haiman, Christopher, Schumacher, Fred, Travis, Ruth, Riboli, Elio, Hunter, David, Gapstur, Susan, Berndt, Sonja, Chanock, Stephen, Han, Younghun, Su, Li, Wei, Yongyue, Hung, Rayjean J., Brhane, Yonathan, McLaughlin, John, Brennan, Paul, McKay, James D., Rosenberger, Albert, Houlston, Richard S., Caporaso, Neil, Teresa Landi, Maria, Heinrich, Joachim, Wu, Xifeng, Ye, Yuanqing, Christiani, David C., Khankari, Nikhil K., Shu, Xiao Ou, Wen, Wanqing, Kraft, Peter, Lindström, Sara, Peters, Ulrike, Schildkraut, Joellen, Schumacher, Fredrick, Bofetta, Paolo, Risch, Angela, Bickeböller, Heike, Amos, Christopher I., Easton, Douglas, Eeles, Rosalind A., Gruber, Stephen B., Haiman, Christopher A., Hunter, David J., Chanock, Stephen J., Pierce, Brandon L., Zheng, Wei, Blalock, Kendra, Campbell, Peter T., Casey, Graham, Conti, David V., Edlund, Christopher K., Figueiredo, Jane, James Gauderman, W., Gong, Jian, Green, Roger C., Harju, John F., Harrison, Tabitha A., Jacobs, Eric J., Jenkins, Mark A., Jiao, Shuo, Li, Li, Lin, Yi, Manion, Frank J., Moreno, Victor, Mukherjee, Bhramar, Raskin, Leon, Schumacher, Fredrick R., Seminara, Daniela, Severi, Gianluca, Stenzel, Stephanie L., Thomas, Duncan C., Hopper, John L., Southey, Melissa C., Makalic, Enes, Schmidt, Daniel F., Fletcher, Olivia, Peto, Julian, Gibson, Lorna, dos Santos Silva, Isabel, Ahsan, Habib, Whittemore, Alice, Waisfisz, Quinten, Meijers-Heijboer, Hanne, Adank, Muriel, van der Luijt, Rob B., Uitterlinden, Andre G., Hofman, Albert, Meindl, Alfons, Schmutzler, Rita K., Müller-Myhsok, Bertram, Lichtner, Peter, Nevanlinna, Heli, Muranen, Taru A., Aittomäki, Kristiina, Blomqvist, Carl, Chang-Claude, Jenny, Hein, Rebecca, Dahmen, Norbert, Beckman, Lars, Crisponi, Laura, Hall, Per, Czene, Kamila, Irwanto, Astrid, Liu, Jianjun, Easton, Douglas F., Turnbull, Clare, Rahman, Nazneen, Eeles, Rosalind, Kote-Jarai, Zsofia, Muir, Kenneth, Giles, Graham, Neal, David, Donovan, Jenny L., Hamdy, Freddie C., Wiklund, Fredrik, Gronberg, Henrik, Haiman, Christopher, Schumacher, Fred, Travis, Ruth, Riboli, Elio, Hunter, David, Gapstur, Susan, Berndt, Sonja, Chanock, Stephen, Han, Younghun, Su, Li, Wei, Yongyue, Hung, Rayjean J., Brhane, Yonathan, McLaughlin, John, Brennan, Paul, McKay, James D., Rosenberger, Albert, Houlston, Richard S., Caporaso, Neil, Teresa Landi, Maria, Heinrich, Joachim, Wu, Xifeng, Ye, Yuanqing, and Christiani, David C.

Published
2016

30. Association between Adult Height and Risk of Colorectal, Lung, and Prostate Cancer: Results from Meta-analyses of Prospective Studies and Mendelian Randomization Analyses

Author

Genetica Sectie Genoomdiagnostiek, Cancer, Khankari, Nikhil K., Shu, Xiao Ou, Wen, Wanqing, Kraft, Peter, Lindström, Sara, Peters, Ulrike, Schildkraut, Joellen, Schumacher, Fredrick, Bofetta, Paolo, Risch, Angela, Bickeböller, Heike, Amos, Christopher I., Easton, Douglas, Eeles, Rosalind A., Gruber, Stephen B., Haiman, Christopher A., Hunter, David J., Chanock, Stephen J., Pierce, Brandon L., Zheng, Wei, Blalock, Kendra, Campbell, Peter T., Casey, Graham, Conti, David V., Edlund, Christopher K., Figueiredo, Jane, James Gauderman, W., Gong, Jian, Green, Roger C., Harju, John F., Harrison, Tabitha A., Jacobs, Eric J., Jenkins, Mark A., Jiao, Shuo, Li, Li, Lin, Yi, Manion, Frank J., Moreno, Victor, Mukherjee, Bhramar, Raskin, Leon, Schumacher, Fredrick R., Seminara, Daniela, Severi, Gianluca, Stenzel, Stephanie L., Thomas, Duncan C., Hopper, John L., Southey, Melissa C., Makalic, Enes, Schmidt, Daniel F., Fletcher, Olivia, Peto, Julian, Gibson, Lorna, dos Santos Silva, Isabel, Ahsan, Habib, Whittemore, Alice, Waisfisz, Quinten, Meijers-Heijboer, Hanne, Adank, Muriel, van der Luijt, Rob B., Uitterlinden, Andre G., Hofman, Albert, Meindl, Alfons, Schmutzler, Rita K., Müller-Myhsok, Bertram, Lichtner, Peter, Nevanlinna, Heli, Muranen, Taru A., Aittomäki, Kristiina, Blomqvist, Carl, Chang-Claude, Jenny, Hein, Rebecca, Dahmen, Norbert, Beckman, Lars, Crisponi, Laura, Hall, Per, Czene, Kamila, Irwanto, Astrid, Liu, Jianjun, Easton, Douglas F., Turnbull, Clare, Rahman, Nazneen, Eeles, Rosalind, Kote-Jarai, Zsofia, Muir, Kenneth, Giles, Graham, Neal, David, Donovan, Jenny L., Hamdy, Freddie C., Wiklund, Fredrik, Gronberg, Henrik, Haiman, Christopher, Schumacher, Fred, Travis, Ruth, Riboli, Elio, Hunter, David, Gapstur, Susan, Berndt, Sonja, Chanock, Stephen, Han, Younghun, Su, Li, Wei, Yongyue, Hung, Rayjean J., Brhane, Yonathan, McLaughlin, John, Brennan, Paul, McKay, James D., Rosenberger, Albert, Houlston, Richard S., Caporaso, Neil, Teresa Landi, Maria, Heinrich, Joachim, Wu, Xifeng, Ye, Yuanqing, Christiani, David C., Genetica Sectie Genoomdiagnostiek, Cancer, Khankari, Nikhil K., Shu, Xiao Ou, Wen, Wanqing, Kraft, Peter, Lindström, Sara, Peters, Ulrike, Schildkraut, Joellen, Schumacher, Fredrick, Bofetta, Paolo, Risch, Angela, Bickeböller, Heike, Amos, Christopher I., Easton, Douglas, Eeles, Rosalind A., Gruber, Stephen B., Haiman, Christopher A., Hunter, David J., Chanock, Stephen J., Pierce, Brandon L., Zheng, Wei, Blalock, Kendra, Campbell, Peter T., Casey, Graham, Conti, David V., Edlund, Christopher K., Figueiredo, Jane, James Gauderman, W., Gong, Jian, Green, Roger C., Harju, John F., Harrison, Tabitha A., Jacobs, Eric J., Jenkins, Mark A., Jiao, Shuo, Li, Li, Lin, Yi, Manion, Frank J., Moreno, Victor, Mukherjee, Bhramar, Raskin, Leon, Schumacher, Fredrick R., Seminara, Daniela, Severi, Gianluca, Stenzel, Stephanie L., Thomas, Duncan C., Hopper, John L., Southey, Melissa C., Makalic, Enes, Schmidt, Daniel F., Fletcher, Olivia, Peto, Julian, Gibson, Lorna, dos Santos Silva, Isabel, Ahsan, Habib, Whittemore, Alice, Waisfisz, Quinten, Meijers-Heijboer, Hanne, Adank, Muriel, van der Luijt, Rob B., Uitterlinden, Andre G., Hofman, Albert, Meindl, Alfons, Schmutzler, Rita K., Müller-Myhsok, Bertram, Lichtner, Peter, Nevanlinna, Heli, Muranen, Taru A., Aittomäki, Kristiina, Blomqvist, Carl, Chang-Claude, Jenny, Hein, Rebecca, Dahmen, Norbert, Beckman, Lars, Crisponi, Laura, Hall, Per, Czene, Kamila, Irwanto, Astrid, Liu, Jianjun, Easton, Douglas F., Turnbull, Clare, Rahman, Nazneen, Eeles, Rosalind, Kote-Jarai, Zsofia, Muir, Kenneth, Giles, Graham, Neal, David, Donovan, Jenny L., Hamdy, Freddie C., Wiklund, Fredrik, Gronberg, Henrik, Haiman, Christopher, Schumacher, Fred, Travis, Ruth, Riboli, Elio, Hunter, David, Gapstur, Susan, Berndt, Sonja, Chanock, Stephen, Han, Younghun, Su, Li, Wei, Yongyue, Hung, Rayjean J., Brhane, Yonathan, McLaughlin, John, Brennan, Paul, McKay, James D., Rosenberger, Albert, Houlston, Richard S., Caporaso, Neil, Teresa Landi, Maria, Heinrich, Joachim, Wu, Xifeng, Ye, Yuanqing, and Christiani, David C.

Published
2016

31. Identification of Susceptibility Loci and Genes for Colorectal Cancer Risk

Author

Zeng, Chenjie, primary, Matsuda, Koichi, additional, Jia, Wei-Hua, additional, Chang, Jiang, additional, Kweon, Sun-Seog, additional, Xiang, Yong-Bing, additional, Shin, Aesun, additional, Jee, Sun Ha, additional, Kim, Dong-Hyun, additional, Zhang, Ben, additional, Cai, Qiuyin, additional, Guo, Xingyi, additional, Long, Jirong, additional, Wang, Nan, additional, Courtney, Regina, additional, Pan, Zhi-Zhong, additional, Wu, Chen, additional, Takahashi, Atsushi, additional, Shin, Min-Ho, additional, Matsuo, Keitaro, additional, Matsuda, Fumihiko, additional, Gao, Yu-Tang, additional, Oh, Jae Hwan, additional, Kim, Soriul, additional, Jung, Keum Ji, additional, Ahn, Yoon-Ok, additional, Ren, Zefang, additional, Li, Hong-Lan, additional, Wu, Jie, additional, Shi, Jiajun, additional, Wen, Wanqing, additional, Yang, Gong, additional, Li, Bingshan, additional, Ji, Bu-Tian, additional, Brenner, Hermann, additional, Schoen, Robert E., additional, Küry, Sébastien, additional, Gruber, Stephen B., additional, Schumacher, Fredrick R., additional, Stenzel, Stephanie L., additional, Casey, Graham, additional, Hopper, John L., additional, Jenkins, Mark A., additional, Kim, Hyeong-Rok, additional, Jeong, Jin-Young, additional, Park, Ji Won, additional, Tajima, Kazuo, additional, Cho, Sang-Hee, additional, Kubo, Michiaki, additional, Shu, Xiao-Ou, additional, Lin, Dongxin, additional, Zeng, Yi-Xin, additional, Zheng, Wei, additional, Baron, John A., additional, Berndt, Sonja I., additional, Bezieau, Stéphane, additional, Caan, Bette J., additional, Carlson, Christopher S., additional, Chan, Andrew T., additional, Chang-Claude, Jenny, additional, Chanock, Stephen J., additional, Conti, David V., additional, Curtis, Keith, additional, Duggan, David, additional, Fuchs, Charles S., additional, Gallinger, Steven, additional, Giovannucci, Edward L., additional, Haile, Robert W., additional, Harrison, Tabitha A., additional, Hayes, Richard B., additional, Hoffmeister, Michael, additional, Hsu, Li, additional, Hudson, Thomas J., additional, Hunter, David J., additional, Hutter, Carolyn M., additional, Jackson, Rebecca D., additional, Jiao, Shuo, additional, Le Marchand, Loic, additional, Lemire, Mathieu, additional, Lindor, Noralane M., additional, Ma, Jing, additional, Newcomb, Polly A., additional, Peters, Ulrike, additional, Potter, John D., additional, Qu, Conghui, additional, Seminara, Daniela, additional, Slattery, Martha L., additional, Thibodeau, Stephen N., additional, White, Emily, additional, Zanke, Brent W., additional, Blalock, Kendra, additional, Campbell, Peter T., additional, Edlund, Christopher K., additional, Figueiredo, Jane, additional, Gauderman, W. James, additional, Gong, Jian, additional, Green, Roger C., additional, Harju, John F., additional, Jacobs, Eric J., additional, Li, Li, additional, Lin, Yi, additional, Manion, Frank J., additional, Moreno, Victor, additional, Mukherjee, Bhramar, additional, Raskin, Leon, additional, Severi, Gianluca, additional, and Thomas, Duncan C., additional

Published
2016
Full Text
View/download PDF

32. Expressing Biomedical Ontologies in Natural Language for Expert Evaluation.

Author

Amith, Muhammad, Manion, Frank J., Harris, Marcelline R., Yaoyun Zhang, Hua Xu, and Cui Tao

Subjects
MEDICAL informatics, MEDICAL language, ARTIFICIAL intelligence, AXIOMS, ONTOLOGY
Abstract

We report on a study of our custom Hootation software for the purposes of assessing its ability to produce clear and accurate natural language phrases from axioms embedded in three biomedical ontologies. Using multiple domain experts and three discrete rating scales, we evaluated the tool on clarity of the natural language produced, fidelity of the natural language produced from the ontology to the axiom, and the fidelity of the domain knowledge represented by the axioms. Results show that Hootation provided relatively clear natural language equivalents for a select set of OWL axioms, although the clarity of statements hinges on the accuracy and representation of axioms in the ontology. [ABSTRACT FROM AUTHOR]

Published
2017
Full Text
View/download PDF

33. Correction: Corrigendum: Genome-wide association study of colorectal cancer identifies six new susceptibility loci

Author

Schumacher, Fredrick R., primary, Schmit, Stephanie L., additional, Jiao, Shuo, additional, Edlund, Christopher K., additional, Wang, Hansong, additional, Zhang, Ben, additional, Hsu, Li, additional, Huang, Shu-Chen, additional, Fischer, Christopher P., additional, Harju, John F., additional, Idos, Gregory E., additional, Lejbkowicz, Flavio, additional, Manion, Frank J., additional, McDonnell, Kevin, additional, McNeil, Caroline E., additional, Melas, Marilena, additional, Rennert, Hedy S., additional, Shi, Wei, additional, Thomas, Duncan C., additional, Van Den Berg, David J., additional, Hutter, Carolyn M., additional, Aragaki, Aaron K., additional, Butterbach, Katja, additional, Caan, Bette J., additional, Carlson, Christopher S., additional, Chanock, Stephen J., additional, Curtis, Keith R., additional, Fuchs, Charles S., additional, Gala, Manish, additional, Giovannucci, Edward L., additional, Gogarten, Stephanie M., additional, Hayes, Richard B., additional, Henderson, Brian, additional, Hunter, David J., additional, Jackson, Rebecca D., additional, Kolonel, Laurence N., additional, Kooperberg, Charles, additional, Küry, Sébastien, additional, LaCroix, Andrea, additional, Laurie, Cathy C., additional, Laurie, Cecelia A., additional, Lemire, Mathieu, additional, Levine, David, additional, Ma, Jing, additional, Makar, Karen W., additional, Qu, Conghui, additional, Taverna, Darin, additional, Ulrich, Cornelia M., additional, Wu, Kana, additional, Kono, Suminori, additional, West, Dee W., additional, Berndt, Sonja I., additional, Bezieau, Stephane, additional, Brenner, Hermann, additional, Campbell, Peter T., additional, Chan, Andrew T., additional, Chang-Claude, Jenny, additional, Coetzee, Gerhard A., additional, Conti, David V., additional, Duggan, David, additional, Figueiredo, Jane C., additional, Fortini, Barbara K., additional, Gallinger, Steven J., additional, Gauderman, W. James, additional, Giles, Graham, additional, Green, Roger, additional, Haile, Robert, additional, Harrison, Tabitha A., additional, Hoffmeister, Michael, additional, Hopper, John L., additional, Hudson, Thomas J., additional, Jacobs, Eric, additional, Iwasaki, Motoki, additional, Jee, Sun Ha, additional, Jenkins, Mark, additional, Jia, Wei-Hua, additional, Joshi, Amit, additional, Li, Li, additional, Lindor, Noralene M., additional, Matsuo, Keitaro, additional, Moreno, Victor, additional, Mukherjee, Bhramar, additional, Newcomb, Polly A., additional, Potter, John D., additional, Raskin, Leon, additional, Rennert, Gad, additional, Rosse, Stephanie, additional, Severi, Gianluca, additional, Schoen, Robert E., additional, Seminara, Daniela, additional, Shu, Xiao-Ou, additional, Slattery, Martha L., additional, Tsugane, Shoichiro, additional, White, Emily, additional, Xiang, Yong-Bing, additional, Zanke, Brent W., additional, Zheng, Wei, additional, Le Marchand, Loic, additional, Casey, Graham, additional, Gruber, Stephen B., additional, and Peters, Ulrike, additional

Published
2015
Full Text
View/download PDF

37. FuGEFlow: data model and markup language for flow cytometry

Author

Qian, Yu, primary, Tchuvatkina, Olga, additional, Spidlen, Josef, additional, Wilkinson, Peter, additional, Gasparetto, Maura, additional, Jones, Andrew R, additional, Manion, Frank J, additional, Scheuermann, Richard H, additional, Sekaly, Rafick-Pierre, additional, and Brinkman, Ryan R, additional

Published
2009
Full Text
View/download PDF

40. Genome-wide association study of colorectal cancer identifies six new susceptibility loci

Author

Fredrick R. Schumacher, Schmit, Stephanie L., Jiao, Shuo, Edlund, Christopher K., Wang, Hansong, Zhang, Ben, Hsu, Li, Huang, Shu-Chen, Fischer, Christopher P., Harju, John F., Idos, Gregory E., Lejbkowicz, Flavio, Manion, Frank J., McDonnell, Kevin, McNeil, Caroline E., Melas, Marilena, Rennert, Hedy S., Shi, Wei, Thomas, Duncan C., Van Den Berg, David J., Hutter, Carolyn M., Aragaki, Aaron K., Butterbach, Katja, Caan, Bette J., Carlson, Christopher S., Chanock, Stephen J., Curtis, Keith R., Fuchs, Charles S., Gala, Manish, Giovannucci, Edward L., Gogarten, Stephanie M., Hayes, Richard B., Henderson, Brian E., Hunter, David J., Jackson, Rebecca D. J., Kolonel, Laurence N., Kooperberg, Charles, Küry, Sébastien, LaCroix, Andrea, Moreno Aguado, Víctor, and Universitat de Barcelona

Subjects
Human genome, Càncer colorectal, Genetics, Genoma humà, Colorectal cancer, Genètica
Abstract

El document inclou una pàgina final amb una correcció (corrigendum). Aquesta, per si sola, té el següent DOI: 10.1038/ncomms9739 i es va publicar al mateix vol. 6. Genetic susceptibility to colorectal cancer is caused by rare pathogenic mutations and common genetic variants that contribute to familial risk. Here we report the results of a two-stage association study with 18,299 cases of colorectal cancer and 19,656 controls, with follow-up of the most statistically significant genetic loci in 4,725 cases and 9,969 controls from two Asian consortia. We describe six new susceptibility loci reaching a genome-wide threshold of P

41. Genome-wide association study of colorectal cancer identifies six new susceptibility loci

Author

Fredrick R. Schumacher, Schmit, Stephanie L., Jiao, Shuo, Edlund, Christopher K., Wang, Hansong, Zhang, Ben, Hsu, Li, Huang, Shu-Chen, Fischer, Christopher P., Harju, John F., Idos, Gregory E., Lejbkowicz, Flavio, Manion, Frank J., McDonnell, Kevin, McNeil, Caroline E., Melas, Marilena, Rennert, Hedy S., Shi, Wei, Thomas, Duncan C., Van Den Berg, David J., Hutter, Carolyn M., Aragaki, Aaron K., Butterbach, Katja, Caan, Bette J., Carlson, Christopher S., Chanock, Stephen J., Curtis, Keith R., Fuchs, Charles S., Gala, Manish, Giovannucci, Edward L., Gogarten, Stephanie M., Hayes, Richard B., Henderson, Brian E., Hunter, David J., Jackson, Rebecca D. J., Kolonel, Laurence N., Kooperberg, Charles, Küry, Sébastien, LaCroix, Andrea, and Moreno Aguado, Víctor

Subjects
Human genome, Càncer colorectal, Genetics, Genoma humà, Colorectal cancer, Genètica
Abstract

El document inclou una pàgina final amb una correcció (corrigendum). Aquesta, per si sola, té el següent DOI: 10.1038/ncomms9739 i es va publicar al mateix vol. 6. Genetic susceptibility to colorectal cancer is caused by rare pathogenic mutations and common genetic variants that contribute to familial risk. Here we report the results of a two-stage association study with 18,299 cases of colorectal cancer and 19,656 controls, with follow-up of the most statistically significant genetic loci in 4,725 cases and 9,969 controls from two Asian consortia. We describe six new susceptibility loci reaching a genome-wide threshold of P

42. Accelerating Evidence Synthesis in Observational Studies: Development of a Living Natural Language Processing-Assisted Intelligent Systematic Literature Review System.

Author

Manion FJ, Du J, Wang D, He L, Lin B, Wang J, Wang S, Eckels D, Cervenka J, Fiduccia PC, Cossrow N, and Yao L

Subjects
Humans, Algorithms, Machine Learning, Software, Natural Language Processing, Observational Studies as Topic methods, Systematic Reviews as Topic
Abstract

Background: Systematic literature review (SLR), a robust method to identify and summarize evidence from published sources, is considered to be a complex, time-consuming, labor-intensive, and expensive task., Objective: This study aimed to present a solution based on natural language processing (NLP) that accelerates and streamlines the SLR process for observational studies using real-world data., Methods: We followed an agile software development and iterative software engineering methodology to build a customized intelligent end-to-end living NLP-assisted solution for observational SLR tasks. Multiple machine learning-based NLP algorithms were adopted to automate article screening and data element extraction processes. The NLP prediction results can be further reviewed and verified by domain experts, following the human-in-the-loop design. The system integrates explainable articificial intelligence to provide evidence for NLP algorithms and add transparency to extracted literature data elements. The system was developed based on 3 existing SLR projects of observational studies, including the epidemiology studies of human papillomavirus-associated diseases, the disease burden of pneumococcal diseases, and cost-effectiveness studies on pneumococcal vaccines., Results: Our Intelligent SLR Platform covers major SLR steps, including study protocol setting, literature retrieval, abstract screening, full-text screening, data element extraction from full-text articles, results summary, and data visualization. The NLP algorithms achieved accuracy scores of 0.86-0.90 on article screening tasks (framed as text classification tasks) and macroaverage F1 scores of 0.57-0.89 on data element extraction tasks (framed as named entity recognition tasks)., Conclusions: Cutting-edge NLP algorithms expedite SLR for observational studies, thus allowing scientists to have more time to focus on the quality of data and the synthesis of evidence in observational studies. Aligning the living SLR concept, the system has the potential to update literature data and enable scientists to easily stay current with the literature related to observational studies prospectively and continuously., (© Frank J Manion, Jingcheng Du, Dong Wang, Long He, Bin Lin, Jingqi Wang, Siwei Wang, David Eckels, Jan Cervenka, Peter C Fiduccia, Nicole Cossrow, Lixia Yao. Originally published in JMIR Medical Informatics (https://medinform.jmir.org).)

Published
2024
Full Text
View/download PDF

43. Enhancing early detection of cognitive decline in the elderly: a comparative study utilizing large language models in clinical notes.

Author

Du X, Novoa-Laurentiev J, Plasek JM, Chuang YW, Wang L, Marshall GA, Mueller SK, Chang F, Datta S, Paek H, Lin B, Wei Q, Wang X, Wang J, Ding H, Manion FJ, Du J, Bates DW, and Zhou L

Abstract

Background: Large language models (LLMs) have shown promising performance in various healthcare domains, but their effectiveness in identifying specific clinical conditions in real medical records is less explored. This study evaluates LLMs for detecting signs of cognitive decline in real electronic health record (EHR) clinical notes, comparing their error profiles with traditional models. The insights gained will inform strategies for performance enhancement., Methods: This study, conducted at Mass General Brigham in Boston, MA, analysed clinical notes from the four years prior to a 2019 diagnosis of mild cognitive impairment in patients aged 50 and older. We developed prompts for two LLMs, Llama 2 and GPT-4, on Health Insurance Portability and Accountability Act (HIPAA)-compliant cloud-computing platforms using multiple approaches (e.g., hard prompting, retrieval augmented generation, and error analysis-based instructions) to select the optimal LLM-based method. Baseline models included a hierarchical attention-based neural network and XGBoost. Subsequently, we constructed an ensemble of the three models using a majority vote approach. Confusion-matrix-based scores were used for model evaluation., Findings: We used a randomly annotated sample of 4949 note sections from 1969 patients (women: 1046 [53.1%]; age: mean, 76.0 [SD, 13.3] years), filtered with keywords related to cognitive functions, for model development. For testing, a random annotated sample of 1996 note sections from 1161 patients (women: 619 [53.3%]; age: mean, 76.5 [SD, 10.2] years) without keyword filtering was utilised. GPT-4 demonstrated superior accuracy and efficiency compared to Llama 2, but did not outperform traditional models. The ensemble model outperformed the individual models in terms of all evaluation metrics with statistical significance (p < 0.01), achieving a precision of 90.2% [95% CI: 81.9%-96.8%], a recall of 94.2% [95% CI: 87.9%-98.7%], and an F1-score of 92.1% [95% CI: 86.8%-96.4%]. Notably, the ensemble model showed a significant improvement in precision, increasing from a range of 70%-79% to above 90%, compared to the best-performing single model. Error analysis revealed that 63 samples were incorrectly predicted by at least one model; however, only 2 cases (3.2%) were mutual errors across all models, indicating diverse error profiles among them., Interpretation: LLMs and traditional machine learning models trained using local EHR data exhibited diverse error profiles. The ensemble of these models was found to be complementary, enhancing diagnostic performance. Future research should investigate integrating LLMs with smaller, localised models and incorporating medical data and domain knowledge to enhance performance on specific tasks., Funding: This research was supported by the National Institute on Aging grants (R44AG081006, R01AG080429) and National Library of Medicine grant (R01LM014239)., Competing Interests: Declaration of interests None., (Copyright © 2024 The Author(s). Published by Elsevier B.V. All rights reserved.)

Published
2024
Full Text
View/download PDF

44. Natural Language Processing-Powered Real-Time Monitoring Solution for Vaccine Sentiments and Hesitancy on Social Media: System Development and Validation.

Author

Huang LC, Eiden AL, He L, Annan A, Wang S, Wang J, Manion FJ, Wang X, Du J, and Yao L

Abstract

Background: Vaccines serve as a crucial public health tool, although vaccine hesitancy continues to pose a significant threat to full vaccine uptake and, consequently, community health. Understanding and tracking vaccine hesitancy is essential for effective public health interventions; however, traditional survey methods present various limitations., Objective: This study aimed to create a real-time, natural language processing (NLP)-based tool to assess vaccine sentiment and hesitancy across 3 prominent social media platforms., Methods: We mined and curated discussions in English from Twitter (subsequently rebranded as X), Reddit, and YouTube social media platforms posted between January 1, 2011, and October 31, 2021, concerning human papillomavirus; measles, mumps, and rubella; and unspecified vaccines. We tested multiple NLP algorithms to classify vaccine sentiment into positive, neutral, or negative and to classify vaccine hesitancy using the World Health Organization's (WHO) 3Cs (confidence, complacency, and convenience) hesitancy model, conceptualizing an online dashboard to illustrate and contextualize trends., Results: We compiled over 86 million discussions. Our top-performing NLP models displayed accuracies ranging from 0.51 to 0.78 for sentiment classification and from 0.69 to 0.91 for hesitancy classification. Explorative analysis on our platform highlighted variations in online activity about vaccine sentiment and hesitancy, suggesting unique patterns for different vaccines., Conclusions: Our innovative system performs real-time analysis of sentiment and hesitancy on 3 vaccine topics across major social networks, providing crucial trend insights to assist campaigns aimed at enhancing vaccine uptake and public health., (©Liang-Chin Huang, Amanda L Eiden, Long He, Augustine Annan, Siwei Wang, Jingqi Wang, Frank J Manion, Xiaoyan Wang, Jingcheng Du, Lixia Yao. Originally published in JMIR Medical Informatics (https://medinform.jmir.org), 21.06.2024.)

Published
2024
Full Text
View/download PDF

45. Expressing and Executing Informed Consent Permissions Using SWRL: The All of Us Use Case.

Author

Amith M, Harris MR, Stansbury C, Ford K, Manion FJ, and Tao C

Subjects
Humans, Informed Consent, Language, Semantics, Population Health, Semantic Web
Abstract

The informed consent process is a complicated procedure involving permissions as well a variety of entities and actions. In this paper, we discuss the use of Semantic Web Rule Language (SWRL) to further extend the Informed Consent Ontology (ICO) to allow for semantic machine-based reasoning to manage and generate important permission-based information that can later be viewed by stakeholders. We present four use cases of permissions from the All of Us informed consent document and translate these permissions into SWRL expressions to extend and operationalize ICO. Our efforts show how SWRL is able to infer some of the implicit information based on the defined rules, and demonstrate the utility of ICO through the use of SWRL extensions. Future work will include developing formal and generalized rules and expressing permissions from the entire document, as well as working towards integrating ICO into software systems to enhance the semantic representation of informed consent for biomedical research., (©2021 AMIA - All rights reserved.)

Published
2022

46. COVID-19 SignSym: a fast adaptation of a general clinical NLP tool to identify and normalize COVID-19 signs and symptoms to OMOP common data model.

Author

Wang J, Abu-El-Rub N, Gray J, Pham HA, Zhou Y, Manion FJ, Liu M, Song X, Xu H, Rouhizadeh M, and Zhang Y

Abstract

The COVID-19 pandemic swept across the world rapidly, infecting millions of people. An efficient tool that can accurately recognize important clinical concepts of COVID-19 from free text in electronic health records (EHRs) will be valuable to accelerate COVID-19 clinical research. To this end, this study aims at adapting the existing CLAMP natural language processing tool to quickly build COVID-19 SignSym, which can extract COVID-19 signs/symptoms and their 8 attributes (body location, severity, temporal expression, subject, condition, uncertainty, negation, and course) from clinical text. The extracted information is also mapped to standard concepts in the Observational Medical Outcomes Partnership common data model. A hybrid approach of combining deep learning-based models, curated lexicons, and pattern-based rules was applied to quickly build the COVID-19 SignSym from CLAMP, with optimized performance. Our extensive evaluation using 3 external sites with clinical notes of COVID-19 patients, as well as the online medical dialogues of COVID-19, shows COVID-19 SignSym can achieve high performance across data sources. The workflow used for this study can be generalized to other use cases, where existing clinical natural language processing tools need to be customized for specific information needs within a short time. COVID-19 SignSym is freely accessible to the research community as a downloadable package (https://clamp.uth.edu/covid/nlp.php) and has been used by 16 healthcare organizations to support clinical research of COVID-19., Competing Interests: CONFLICT OF INTEREST STATEMENT Dr Hua Xu, Mr Jingqi Wang, and The University of Texas Health Science Center at Houston have financial related research interest in Melax Technologies, Inc.

Published
2020

47. Novel Common Genetic Susceptibility Loci for Colorectal Cancer.

Author

Schmit SL, Edlund CK, Schumacher FR, Gong J, Harrison TA, Huyghe JR, Qu C, Melas M, Van Den Berg DJ, Wang H, Tring S, Plummer SJ, Albanes D, Alonso MH, Amos CI, Anton K, Aragaki AK, Arndt V, Barry EL, Berndt SI, Bezieau S, Bien S, Bloomer A, Boehm J, Boutron-Ruault MC, Brenner H, Brezina S, Buchanan DD, Butterbach K, Caan BJ, Campbell PT, Carlson CS, Castelao JE, Chan AT, Chang-Claude J, Chanock SJ, Cheng I, Cheng YW, Chin LS, Church JM, Church T, Coetzee GA, Cotterchio M, Cruz Correa M, Curtis KR, Duggan D, Easton DF, English D, Feskens EJM, Fischer R, FitzGerald LM, Fortini BK, Fritsche LG, Fuchs CS, Gago-Dominguez M, Gala M, Gallinger SJ, Gauderman WJ, Giles GG, Giovannucci EL, Gogarten SM, Gonzalez-Villalpando C, Gonzalez-Villalpando EM, Grady WM, Greenson JK, Gsur A, Gunter M, Haiman CA, Hampe J, Harlid S, Harju JF, Hayes RB, Hofer P, Hoffmeister M, Hopper JL, Huang SC, Huerta JM, Hudson TJ, Hunter DJ, Idos GE, Iwasaki M, Jackson RD, Jacobs EJ, Jee SH, Jenkins MA, Jia WH, Jiao S, Joshi AD, Kolonel LN, Kono S, Kooperberg C, Krogh V, Kuehn T, Küry S, LaCroix A, Laurie CA, Lejbkowicz F, Lemire M, Lenz HJ, Levine D, Li CI, Li L, Lieb W, Lin Y, Lindor NM, Liu YR, Loupakis F, Lu Y, Luh F, Ma J, Mancao C, Manion FJ, Markowitz SD, Martin V, Matsuda K, Matsuo K, McDonnell KJ, McNeil CE, Milne R, Molina AJ, Mukherjee B, Murphy N, Newcomb PA, Offit K, Omichessan H, Palli D, Cotoré JPP, Pérez-Mayoral J, Pharoah PD, Potter JD, Qu C, Raskin L, Rennert G, Rennert HS, Riggs BM, Schafmayer C, Schoen RE, Sellers TA, Seminara D, Severi G, Shi W, Shibata D, Shu XO, Siegel EM, Slattery ML, Southey M, Stadler ZK, Stern MC, Stintzing S, Taverna D, Thibodeau SN, Thomas DC, Trichopoulou A, Tsugane S, Ulrich CM, van Duijnhoven FJB, van Guelpan B, Vijai J, Virtamo J, Weinstein SJ, White E, Win AK, Wolk A, Woods M, Wu AH, Wu K, Xiang YB, Yen Y, Zanke BW, Zeng YX, Zhang B, Zubair N, Kweon SS, Figueiredo JC, Zheng W, Marchand LL, Lindblom A, Moreno V, Peters U, Casey G, Hsu L, Conti DV, and Gruber SB

Subjects
Case-Control Studies, Ethnicity statistics & numerical data, Follow-Up Studies, Genotype, Humans, Prognosis, United States epidemiology, Colorectal Neoplasms epidemiology, Colorectal Neoplasms genetics, Ethnicity genetics, Genetic Loci, Genetic Predisposition to Disease, Genome-Wide Association Study, Polymorphism, Single Nucleotide
Abstract

Background: Previous genome-wide association studies (GWAS) have identified 42 loci (P < 5 × 10-8) associated with risk of colorectal cancer (CRC). Expanded consortium efforts facilitating the discovery of additional susceptibility loci may capture unexplained familial risk., Methods: We conducted a GWAS in European descent CRC cases and control subjects using a discovery-replication design, followed by examination of novel findings in a multiethnic sample (cumulative n = 163 315). In the discovery stage (36 948 case subjects/30 864 control subjects), we identified genetic variants with a minor allele frequency of 1% or greater associated with risk of CRC using logistic regression followed by a fixed-effects inverse variance weighted meta-analysis. All novel independent variants reaching genome-wide statistical significance (two-sided P < 5 × 10-8) were tested for replication in separate European ancestry samples (12 952 case subjects/48 383 control subjects). Next, we examined the generalizability of discovered variants in East Asians, African Americans, and Hispanics (12 085 case subjects/22 083 control subjects). Finally, we examined the contributions of novel risk variants to familial relative risk and examined the prediction capabilities of a polygenic risk score. All statistical tests were two-sided., Results: The discovery GWAS identified 11 variants associated with CRC at P < 5 × 10-8, of which nine (at 4q22.2/5p15.33/5p13.1/6p21.31/6p12.1/10q11.23/12q24.21/16q24.1/20q13.13) independently replicated at a P value of less than .05. Multiethnic follow-up supported the generalizability of discovery findings. These results demonstrated a 14.7% increase in familial relative risk explained by common risk alleles from 10.3% (95% confidence interval [CI] = 7.9% to 13.7%; known variants) to 11.9% (95% CI = 9.2% to 15.5%; known and novel variants). A polygenic risk score identified 4.3% of the population at an odds ratio for developing CRC of at least 2.0., Conclusions: This study provides insight into the architecture of common genetic variation contributing to CRC etiology and improves risk prediction for individualized screening., (© The Author(s) 2018. Published by Oxford University Press. All rights reserved. For permissions, please email: journals.permissions@oup.com.)

Published
2019
Full Text
View/download PDF

48. Expressing Biomedical Ontologies in Natural Language for Expert Evaluation.

Author

Amith M, Manion FJ, Harris MR, Zhang Y, Xu H, and Tao C

Subjects
Knowledge, Language, Software, Biological Ontologies, Natural Language Processing
Abstract

We report on a study of our custom Hootation software for the purposes of assessing its ability to produce clear and accurate natural language phrases from axioms embedded in three biomedical ontologies. Using multiple domain experts and three discrete rating scales, we evaluated the tool on clarity of the natural language produced, fidelity of the natural language produced from the ontology to the axiom, and the fidelity of the domain knowledge represented by the axioms. Results show that Hootation provided relatively clear natural language equivalents for a select set of OWL axioms, although the clarity of statements hinges on the accuracy and representation of axioms in the ontology.

Published
2017

49. Hedging their mets: the use of uncertainty terms in clinical documents and its potential implications when sharing the documents with patients.

Author

Hanauer DA, Liu Y, Mei Q, Manion FJ, Balis UJ, and Zheng K

Subjects
Humans, Medical Records Systems, Computerized, Physicians, Electronic Health Records, Language, Natural Language Processing, Patient Access to Records
Abstract

In this study, we quantified the use of uncertainty expressions, referred to as 'hedge' phrases, among a corpus of 100,000 clinical documents retrieved from our institution's electronic health record system. The frequency of each hedge phrase appearing in the corpus was characterized across document types and clinical departments. We also used a natural language processing tool to identify clinical concepts that were spatially, and potentially semantically, associated with the hedge phrases identified. The objective was to delineate the prevalence of hedge phrase usage in clinical documentation which may have a profound impact on patient care and provider-patient communication, and may become a source of unintended consequences when such documents are made directly accessible to patients via patient portals.

Published
2012

50. Voice-dictated versus typed-in clinician notes: linguistic properties and the potential implications on natural language processing.

Author

Zheng K, Mei Q, Yang L, Manion FJ, Balis UJ, and Hanauer DA

Subjects
Humans, Narration, User-Computer Interface, Computer Peripherals, Electronic Health Records, Linguistics, Medical Records, Natural Language Processing, Speech Recognition Software
Abstract

In this study, we comparatively examined the linguistic properties of narrative clinician notes created through voice dictation versus those directly entered by clinicians via a computer keyboard. Intuitively, the nature of voice-dictated notes would resemble that of natural language, while typed-in notes may demonstrate distinctive language features for reasons such as intensive usage of acronyms. The study analyses were based on an empirical dataset retrieved from our institutional electronic health records system. The dataset contains 30,000 voice-dictated notes and 30,000 notes that were entered manually; both were encounter notes generated in ambulatory care settings. The results suggest that between the narrative clinician notes created via these two different methods, there exists a considerable amount of lexical and distributional differences. Such differences could have a significant impact on the performance of natural language processing tools, necessitating these two different types of documents being differentially treated.

Published
2011

Catalog

Books, media, physical & digital resources
See catalog results