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1. Circular-SWAT for deep learning based diagnostic classification of Alzheimer's disease: application to metabolome data

Author

Jo, Taeho, Kim, Junpyo, Bice, Paula, Huynh, Kevin, Wang, Tingting, Arnold, Matthias, Meikle, Peter J, Giles, Corey, Kaddurah-Daouk, Rima, Saykin, Andrew J, Nho, Kwangsik, Kueider-Paisley, Alexandra, Doraiswamy, P Murali, Blach, Colette, Moseley, Arthur, Thompson, Will, St John-Williams, Lisa, Mahmoudiandehkhordi, Siamak, Tenenbaum, Jessica, Welsh-Balmer, Kathleen, Plassman, Brenda, Risacher, Shannon L, Kastenmüller, Gabi, Han, Xianlin, Baillie, Rebecca, Knight, Rob, Dorrestein, Pieter, Brewer, James, Mayer, Emeran, Labus, Jennifer, Baldi, Pierre, Gupta, Arpana, Fiehn, Oliver, Barupal, Dinesh, Meikle, Peter, Mazmanian, Sarkis, Rader, Dan, Kling, Mitchel, Shaw, Leslie, Trojanowski, John, van Duijin, Cornelia, Nevado-Holgado, Alejo, Bennett, David, Krishnan, Ranga, Keshavarzian, Ali, Vogt, Robin, Ikram, Arfan, Hankemeier, Thomas, Thiele, Ines, Price, Nathan, Funk, Cory, Baloni, Priyanka, Jia, Wei, Wishart, David, Brinton, Roberta, Chang, Rui, Farrer, Lindsay, Au, Rhoda, Qiu, Wendy, Würtz, Peter, Koal, Therese, Mangravite, Lara, Krumsiek, Jan, Suhre, Karsten, Newman, John, Moreno, Herman, Foroud, Tatania, Sacks, Frank, Jansson, Janet, Weiner, Michael W, Aisen, Paul, Petersen, Ronald, Jack, Clifford R, Jagust, William, Trojanowki, John Q, Toga, Arthur W, Beckett, Laurel, Green, Robert C, Morris, John C, Perrin, Richard J, Shaw, Leslie M, Khachaturian, Zaven, Carrillo, Maria, Potter, William, Barnes, Lisa, Bernard, Marie, Gonzalez, Hector, Ho, Carole, Hsiao, John K, Jackson, Jonathan, Masliah, Eliezer, Masterman, Donna, Okonkwo, Ozioma, Perrin, Richard, and Ryan, Laurie

Subjects
Medical Biochemistry and Metabolomics, Biomedical and Clinical Sciences, Neurosciences, Acquired Cognitive Impairment, Alzheimer's Disease including Alzheimer's Disease Related Dementias (AD/ADRD), Networking and Information Technology R&D (NITRD), Machine Learning and Artificial Intelligence, Dementia, Aging, Brain Disorders, Alzheimer's Disease, Neurodegenerative, Neurological, Humans, Aged, Magnetic Resonance Imaging, Deep Learning, Alzheimer Disease, Neuroimaging, Metabolome, Lipids, Cognitive Dysfunction, Alzheimer's Disease Metabolomics Consortium, Alzheimer's Disease Neuroimaging Initiative, Alzheimer's disease, Deep learning, Lipidomics, Machine learning, Metabolomics, Clinical Sciences, Public Health and Health Services, Clinical sciences, Epidemiology
Abstract

BackgroundDeep learning has shown potential in various scientific domains but faces challenges when applied to complex, high-dimensional multi-omics data. Alzheimer's Disease (AD) is a neurodegenerative disorder that lacks targeted therapeutic options. This study introduces the Circular-Sliding Window Association Test (c-SWAT) to improve the classification accuracy in predicting AD using serum-based metabolomics data, specifically lipidomics.MethodsThe c-SWAT methodology builds upon the existing Sliding Window Association Test (SWAT) and utilizes a three-step approach: feature correlation analysis, feature selection, and classification. Data from 997 participants from the Alzheimer's Disease Neuroimaging Initiative (ADNI) served as the basis for model training and validation. Feature correlations were analyzed using Weighted Gene Co-expression Network Analysis (WGCNA), and Convolutional Neural Networks (CNN) were employed for feature selection. Random Forest was used for the final classification.FindingsThe application of c-SWAT resulted in a classification accuracy of up to 80.8% and an AUC of 0.808 for distinguishing AD from cognitively normal older adults. This marks a 9.4% improvement in accuracy and a 0.169 increase in AUC compared to methods without c-SWAT. These results were statistically significant, with a p-value of 1.04 × 10ˆ-4. The approach also identified key lipids associated with AD, such as Cer(d16:1/22:0) and PI(37:6).InterpretationOur results indicate that c-SWAT is effective in improving classification accuracy and in identifying potential lipid biomarkers for AD. These identified lipids offer new avenues for understanding AD and warrant further investigation.FundingThe specific funding of this article is provided in the acknowledgements section.

Published
2023

2. Circular-SWAT for deep learning based diagnostic classification of Alzheimer's disease: application to metabolome data

Author

Kaddurah-Daouk, Rima, Kueider-Paisley, Alexandra, Doraiswamy, P. Murali, Blach, Colette, Moseley, Arthur, Thompson, Will, St John-Williams, Lisa, Mahmoudiandehkhordi, Siamak, Tenenbaum, Jessica, Welsh-Balmer, Kathleen, Plassman, Brenda, Saykin, Andrew J., Nho, Kwangsik, Risacher, Shannon L., Kastenmüller, Gabi, Arnold, Matthias, Han, Xianlin, Baillie, Rebecca, Knight, Rob, Dorrestein, Pieter, Brewer, James, Mayer, Emeran, Labus, Jennifer, Baldi, Pierre, Gupta, Arpana, Fiehn, Oliver, Barupal, Dinesh, Meikle, Peter, Mazmanian, Sarkis, Rader, Dan, Kling, Mitchel, Shaw, Leslie, Trojanowski, John, van Duijin, Cornelia, Nevado-Holgado, Alejo, Bennett, David, Krishnan, Ranga, Keshavarzian, Ali, Vogt, Robin, Ikram, Arfan, Hankemeier, Thomas, Thiele, Ines, Price, Nathan, Funk, Cory, Baloni, Priyanka, Jia, Wei, Wishart, David, Brinton, Roberta, Chang, Rui, Farrer, Lindsay, Au, Rhoda, Qiu, Wendy, Würtz, Peter, Koal, Therese, Mangravite, Lara, Krumsiek, Jan, Suhre, Karsten, Newman, John, Moreno, Herman, Foroud, Tatania, Sacks, Frank, Jansson, Janet, Weiner, Michael W., Aisen, Paul, Petersen, Ronald, Jack, Clifford R., Jr., Jagust, William, Trojanowki, John Q., Toga, Arthur W., Beckett, Laurel, Green, Robert C., Morris, John C., Perrin, Richard J., Shaw, Leslie M., Khachaturian, Zaven, Carrillo, Maria, Potter, William, Barnes, Lisa, Bernard, Marie, Gonzalez, Hector, Ho, Carole, Hsiao, John K., Jackson, Jonathan, Masliah, Eliezer, Masterman, Donna, Okonkwo, Ozioma, Perrin, Richard, Ryan, Laurie, Silverberg, Nina, Fleisher, Adam, Sacrey, Diana Truran, Fockler, Juliet, Conti, Cat, Veitch, Dallas, Neuhaus, John, Jin, Chengshi, Nosheny, Rachel, Ashford, Miriam, Flenniken, Derek, Kormos, Adrienne, Montine, Tom, Rafii, Michael, Raman, Rema, Jimenez, Gustavo, Donohue, Michael, Gessert, Devon, Salazar, Jennifer, Zimmerman, Caileigh, Cabrera, Yuliana, Walter, Sarah, Miller, Garrett, Coker, Godfrey, Clanton, Taylor, Hergesheimer, Lindsey, Smith, Stephanie, Adegoke, Olusegun, Mahboubi, Payam, Moore, Shelley, Pizzola, Jeremy, Shaffer, Elizabeth, Sloan, Brittany, Harvey, Danielle, Forghanian-Arani, Arvin, Borowski, Bret, Ward, Chad, Schwarz, Christopher, Jones, David, Gunter, Jeff, Kantarci, Kejal, Senjem, Matthew, Vemuri, Prashanthi, Reid, Robert, Fox, Nick C., Malone, Ian, Thompson, Paul, Thomopoulos, Sophia I., Nir, Talia M., Jahanshad, Neda, DeCarli, Charles, Knaack, Alexander, Fletcher, Evan, Tosun-Turgut, Duygu, Chen, Stephanie Rossi, Choe, Mark, Crawford, Karen, Yushkevich, Paul A., Das, Sandhitsu, Koeppe, Robert A., Reiman, Eric M., Chen, Kewei, Mathis, Chet, Landau, Susan, Cairns, Nigel J., Householder, Erin, Franklin, Erin, Bernhardt, Haley, Taylor-Reinwald, Lisa, Korecka, Magdalena, Figurski, Michal, Neu, Scott, Apostolova, Liana G., Shen, Li, Foroud, Tatiana M., Nudelman, Kelly, Faber, Kelley, Wilmes, Kristi, Thal, Leon, Silbert, Lisa C., Lind, Betty, Crissey, Rachel, Kaye, Jeffrey A., Carter, Raina, Dolen, Sara, Quinn, Joseph, Schneider, Lon S., Pawluczyk, Sonia, Becerra, Mauricio, Teodoro, Liberty, Dagerman, Karen, Spann, Bryan M., Vanderswag, Helen, Ziolkowski, Jaimie, Heidebrink, Judith L., Zbizek-Nulph, Lisa, Lord, Joanne L., Mason, Sara S., Albers, Colleen S., Knopman, David, Johnson, Kris, Villanueva-Meyer, Javier, Pavlik, Valory, Pacini, Nathaniel, Lamb, Ashley, Kass, Joseph S., Doody, Rachelle S., Shibley, Victoria, Chowdhury, Munir, Rountree, Susan, Dang, Mimi, Stern, Yaakov, Honig, Lawrence S., Mintz, Akiva, Ances, Beau, Winkfield, David, Carroll, Maria, Stobbs-Cucchi, Georgia, Oliver, Angela, Creech, Mary L., Mintun, Mark A., Schneider, Stacy, Geldmacher, David, Love, Marissa Natelson, Griffith, Randall, Clark, David, Brockington, John, Marson, Daniel, Grossman, Hillel, Goldstein, Martin A., Greenberg, Jonathan, Mitsis, Effie, Shah, Raj C., Lamar, Melissa, Samuels, Patricia, Duara, Ranjan, Greig-Custo, Maria T., Rodriguez, Rosemarie, Albert, Marilyn, Onyike, Chiadi, Farrington, Leonie, Rudow, Scott, Brichko, Rottislav, Kielb, Stephanie, Smith, Amanda, Raj, Balebail Ashok, Fargher, Kristin, Sadowski, Martin, Wisniewski, Thomas, Shulman, Melanie, Faustin, Arline, Rao, Julia, Castro, Karen M., Ulysse, Anaztasia, Chen, Shannon, Sheikh, Mohammed O., Singleton-Garvin, Jamika, Petrella, JeffreyR., James, Olga, Wong, Terence Z., Borges-Neto, Salvador, Karlawish, Jason H., Wolk, David A., Vaishnavi, Sanjeev, Clark, Christopher M., Arnold, Steven E., Smith, Charles D., Jicha, Gregory A., Raslau, Flavius D., Lopez, Oscar L., Oakley, MaryAnn, Simpson, Donna M., Porsteinsson, Anton P., Martin, Kim, Kowalski, Nancy, Keltz, Melanie, Goldstein, Bonnie S., Makino, Kelly M., Ismail, M. Saleem, Brand, Connie, Thai, Gaby, Pierce, Aimee, Yanez, Beatriz, Sosa, Elizabeth, Witbracht, Megan, Kelley, Brendan, Nguyen, Trung, Womack, Kyle, Mathews, Dana, Quiceno, Mary, Levey, Allan I., Lah, James J., Hajjar, Ihab, Cellar, Janet S., Burns, Jeffrey M., Swerdlow, Russell H., Brooks, William M., Silverman, Daniel H.S., Kremen, Sarah, Apostolova, Liana, Tingus, Kathleen, Lu, Po H., Bartzokis, George, Woo, Ellen, Teng, Edmond, Graff-Radford, Neill R., Parfitt, Francine, Poki-Walker, Kim, Farlow, Martin R., Hake, Ann Marie, Matthews, Brandy R., Brosch, Jared R., Herring, Scott, van, Christopher H., Mecca, Adam P., Good, Susan P., MacAvoy, Martha G., Carson, Richard E., Varma, Pradeep, Chertkow, Howard, Vaitekunis, Susan, Hosein, Chris, Black, Sandra, Stefanovic, Bojana, Heyn, Chris (Chinthaka), Robin Hsiung, Ging-Yuek, Kim, Ellen, Mudge, Benita, Sossi, Vesna, Feldman, Howard, Assaly, Michele, Finger, Elizabeth, Pasternak, Stephen, Rachinsky, Irina, Kertesz, Andrew, Drost, Dick, Rogers, John, Grant, Ian, Muse, Brittanie, Rogalski, Emily, Robson, Jordan, Mesulam, M.-Marsel, Kerwin, Diana, Wu, Chuang-Kuo, Johnson, Nancy, Lipowski, Kristine, Weintraub, Sandra, Bonakdarpour, Borna, Pomara, Nunzio, Hernando, Raymundo, Sarrael, Antero, Rosen, Howard J., Miller, Bruce L., Perry, David, Turner, Raymond Scott, Johnson, Kathleen, Reynolds, Brigid, MCCann, Kelly, Poe, Jessica, Sperling, Reisa A., Johnson, Keith A., Marshall, Gad A., Yesavage, Jerome, Taylor, Joy L., Chao, Steven, Coleman, Jaila, White, Jessica D., Lane, Barton, Rosen, Allyson, Tinklenberg, Jared, Belden, Christine M., Atri, Alireza, Clark, Kelly A., Zamrini, Edward, Sabbagh, Marwan, Killiany, Ronald, Stern, Robert, Mez, Jesse, Kowall, Neil, Budson, Andrew E., Obisesan, Thomas O., Ntekim, Oyonumo E., Wolday, Saba, Khan, Javed I., Nwulia, Evaristus, Nadarajah, Sheeba, Lerner, Alan, Ogrocki, Paula, Tatsuoka, Curtis, Fatica, Parianne, Maillard, Pauline, Olichney, John, Carmichael, Owen, Bates, Vernice, Capote, Horacio, Rainka, Michelle, Borrie, Michael, Lee, T.-Y., Bartha, Dr Rob, Johnson, Sterling, Asthana, Sanjay, Carlsson, Cynthia M., Perrin, Allison, Burke, Anna, Scharre, Douglas W., Kataki, Maria, Tarawneh, Rawan, Hart, David, Zimmerman, Earl A., Celmins, Dzintra, Miller, Delwyn D., BolesPonto, Laura L., Smith, Karen Ekstam, Koleva, Hristina, Shim, Hyungsub, Nam, Ki Won, Schultz, Susan K., Williamson, Jeff D., Craft, Suzanne, Cleveland, Jo, Yang, Mia, Sink, Kaycee M., Ott, Brian R., Drake, Jonathan, Tremont, Geoffrey, Daiello, Lori A., Drake, Jonathan D., Ritter, Aaron, Bernick, Charles, Munic, Donna, O'Connelll, Abigail, Mintzer, Jacobo, Wiliams, Arthur, Masdeu, Joseph, Shi, Jiong, Garcia, Angelica, Newhouse, Paul, Potkin, Steven, Salloway, Stephen, Malloy, Paul, Correia, Stephen, Kittur, Smita, Pearlson, Godfrey D., Blank, Karen, Anderson, Karen, Flashman, Laura A., Seltzer, Marc, Hynes, Mary L., Santulli, Robert B., Relkin, Norman, Chiang, Gloria, Lee, Athena, Lin, Michael, Ravdin, Lisa, Petersen, Ron, Neylan, Thomas, Grafman, Jordan, Danowski, Sarah, Nguyen-Barrera, Catherine, Hayes, Jacqueline, Finley, Shannon, Bernstein, Matthew, Senjem, Matt, Foster, Norm, Kim, Sungeun, Sood, Ajay, Blanchard, Kimberly S., Fleischman, Debra, Arfanakis, Konstantinos, Varon, Daniel, Greig, Maria T., Petrella, Jeffrey R., Goldstein, Bonnie, Martin, Kimberly S., Reist, Christopher, Sadowsky, Carl, Martinez, Walter, Villena, Teresa, Rosen, Howard, Marshall, Gad, Peskind, Elaine R., Petrie, Eric C., Li, Gail, Mackin, Scott, Jimenez-Maggiora, Gustavo, Drake, Erin, Donohue, Mike, Nelson, Craig, Bickford, David, Butters, Meryl, Zmuda, Michelle, Reyes, Denise, Faber, Kelley M., Nudelman, Kelly N., Au, Yiu Ho, Scherer, Kelly, Catalinotto, Daniel, Stark, Samuel, Ong, Elise, Fernandez, Dariella, Jo, Taeho, Kim, Junpyo, Bice, Paula, Huynh, Kevin, Wang, Tingting, Meikle, Peter J., and Giles, Corey

Published
2023
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3. Peripheral inflammation is associated with brain atrophy and cognitive decline linked to mild cognitive impairment and Alzheimer’s disease

Author

Liang, Nuanyi, Nho, Kwangsik, Newman, John W., Arnold, Matthias, Huynh, Kevin, Meikle, Peter J., Borkowski, Kamil, Kaddurah-Daouk, Rima, Kueider-Paisley, Alexandra, Doraiswamy, P. Murali, Blach, Colette, Moseley, Arthur, Mahmoudiandehkhordi, Siamak, Welsh-Balmer, Kathleen, Plassman, Brenda, Saykin, Andrew, Risacher, Shannon, Kastenmüller, Gabi, Han, Xianlin, Baillie, Rebecca, Knight, Rob, Dorrestein, Pieter, Brewer, James, Mayer, Emeran, Labus, Jennifer, Baldi, Pierre, Gupta, Arpana, Fiehn, Oliver, Barupal, Dinesh, Meikle, Peter, Mazmanian, Sarkis, Rader, Dan, Shaw, Leslie, van Duijin, Cornelia, Amin, Najaf, Nevado-Holgado, Alejo, Bennett, David, Krishnan, Ranga, Keshavarzian, Ali, Vogt, Robin, Ikram, Arfan, Hankemeier, Thomas, Thiele, Ines, Funk, Cory, Baloni, Priyanka, Jia, Wei, Wishart, David, Brinton, Roberta, Farrer, Lindsay, Au, Rhoda, Liang, Nuanyi, Nho, Kwangsik, Newman, John W., Arnold, Matthias, Huynh, Kevin, Meikle, Peter J., Borkowski, Kamil, Kaddurah-Daouk, Rima, Kueider-Paisley, Alexandra, Doraiswamy, P. Murali, Blach, Colette, Moseley, Arthur, Mahmoudiandehkhordi, Siamak, Welsh-Balmer, Kathleen, Plassman, Brenda, Saykin, Andrew, Risacher, Shannon, Kastenmüller, Gabi, Han, Xianlin, Baillie, Rebecca, Knight, Rob, Dorrestein, Pieter, Brewer, James, Mayer, Emeran, Labus, Jennifer, Baldi, Pierre, Gupta, Arpana, Fiehn, Oliver, Barupal, Dinesh, Meikle, Peter, Mazmanian, Sarkis, Rader, Dan, Shaw, Leslie, van Duijin, Cornelia, Amin, Najaf, Nevado-Holgado, Alejo, Bennett, David, Krishnan, Ranga, Keshavarzian, Ali, Vogt, Robin, Ikram, Arfan, Hankemeier, Thomas, Thiele, Ines, Funk, Cory, Baloni, Priyanka, Jia, Wei, Wishart, David, Brinton, Roberta, Farrer, Lindsay, and Au, Rhoda

Abstract

Inflammation is an important factor in Alzheimer’s disease (AD). An NMR measurement in plasma, glycoprotein acetyls (GlycA), captures the overall level of protein production and glycosylation implicated in systemic inflammation. With its additional advantage of reducing biological variability, GlycA might be useful in monitoring the relationship between peripheral inflammation and brain changes relevant to AD. However, the associations between GlycA and these brain changes have not been fully evaluated. Here, we performed Spearman’s correlation analyses to evaluate these associations cross-sectionally and determined whether GlycA can inform AD-relevant longitudinal measurements among participants in the Alzheimer’s Disease Neuroimaging Initiative (n = 1506), with additional linear models and stratification analyses to evaluate the influences of sex or diagnosis status and confirm findings from Spearman’s correlation analyses. We found that GlycA was elevated in AD patients compared to cognitively normal participants. GlycA correlated negatively with multiple concurrent regional brain volumes in females diagnosed with late mild cognitive impairment (LMCI) or AD. Baseline GlycA level was associated with executive function decline at 3–9 year follow-up in participants diagnosed with LMCI at baseline, with similar but not identical trends observed in the future decline of memory and entorhinal cortex volume. Results here indicated that GlycA is an inflammatory biomarker relevant to AD pathogenesis and that the stage of LMCI might be relevant to inflammation-related intervention.

Published
2024

4. Circular-SWAT for deep learning based diagnostic classification of Alzheimer's disease: application to metabolome data

Author

Jo, Taeho, primary, Kim, Junpyo, additional, Bice, Paula, additional, Huynh, Kevin, additional, Wang, Tingting, additional, Arnold, Matthias, additional, Meikle, Peter J., additional, Giles, Corey, additional, Kaddurah-Daouk, Rima, additional, Saykin, Andrew J., additional, Nho, Kwangsik, additional, Kueider-Paisley, Alexandra, additional, Doraiswamy, P. Murali, additional, Blach, Colette, additional, Moseley, Arthur, additional, Thompson, Will, additional, St John-Williams, Lisa, additional, Mahmoudiandehkhordi, Siamak, additional, Tenenbaum, Jessica, additional, Welsh-Balmer, Kathleen, additional, Plassman, Brenda, additional, Risacher, Shannon L., additional, Kastenmüller, Gabi, additional, Han, Xianlin, additional, Baillie, Rebecca, additional, Knight, Rob, additional, Dorrestein, Pieter, additional, Brewer, James, additional, Mayer, Emeran, additional, Labus, Jennifer, additional, Baldi, Pierre, additional, Gupta, Arpana, additional, Fiehn, Oliver, additional, Barupal, Dinesh, additional, Meikle, Peter, additional, Mazmanian, Sarkis, additional, Rader, Dan, additional, Kling, Mitchel, additional, Shaw, Leslie, additional, Trojanowski, John, additional, van Duijin, Cornelia, additional, Nevado-Holgado, Alejo, additional, Bennett, David, additional, Krishnan, Ranga, additional, Keshavarzian, Ali, additional, Vogt, Robin, additional, Ikram, Arfan, additional, Hankemeier, Thomas, additional, Thiele, Ines, additional, Price, Nathan, additional, Funk, Cory, additional, Baloni, Priyanka, additional, Jia, Wei, additional, Wishart, David, additional, Brinton, Roberta, additional, Chang, Rui, additional, Farrer, Lindsay, additional, Au, Rhoda, additional, Qiu, Wendy, additional, Würtz, Peter, additional, Koal, Therese, additional, Mangravite, Lara, additional, Krumsiek, Jan, additional, Suhre, Karsten, additional, Newman, John, additional, Moreno, Herman, additional, Foroud, Tatania, additional, Sacks, Frank, additional, Jansson, Janet, additional, Weiner, Michael W., additional, Aisen, Paul, additional, Petersen, Ronald, additional, Jack, Clifford R., additional, Jagust, William, additional, Trojanowki, John Q., additional, Toga, Arthur W., additional, Beckett, Laurel, additional, Green, Robert C., additional, Morris, John C., additional, Perrin, Richard J., additional, Shaw, Leslie M., additional, Khachaturian, Zaven, additional, Carrillo, Maria, additional, Potter, William, additional, Barnes, Lisa, additional, Bernard, Marie, additional, Gonzalez, Hector, additional, Ho, Carole, additional, Hsiao, John K., additional, Jackson, Jonathan, additional, Masliah, Eliezer, additional, Masterman, Donna, additional, Okonkwo, Ozioma, additional, Perrin, Richard, additional, Ryan, Laurie, additional, Silverberg, Nina, additional, Fleisher, Adam, additional, Sacrey, Diana Truran, additional, Fockler, Juliet, additional, Conti, Cat, additional, Veitch, Dallas, additional, Neuhaus, John, additional, Jin, Chengshi, additional, Nosheny, Rachel, additional, Ashford, Miriam, additional, Flenniken, Derek, additional, Kormos, Adrienne, additional, Montine, Tom, additional, Rafii, Michael, additional, Raman, Rema, additional, Jimenez, Gustavo, additional, Donohue, Michael, additional, Gessert, Devon, additional, Salazar, Jennifer, additional, Zimmerman, Caileigh, additional, Cabrera, Yuliana, additional, Walter, Sarah, additional, Miller, Garrett, additional, Coker, Godfrey, additional, Clanton, Taylor, additional, Hergesheimer, Lindsey, additional, Smith, Stephanie, additional, Adegoke, Olusegun, additional, Mahboubi, Payam, additional, Moore, Shelley, additional, Pizzola, Jeremy, additional, Shaffer, Elizabeth, additional, Sloan, Brittany, additional, Harvey, Danielle, additional, Forghanian-Arani, Arvin, additional, Borowski, Bret, additional, Ward, Chad, additional, Schwarz, Christopher, additional, Jones, David, additional, Gunter, Jeff, additional, Kantarci, Kejal, additional, Senjem, Matthew, additional, Vemuri, Prashanthi, additional, Reid, Robert, additional, Fox, Nick C., additional, Malone, Ian, additional, Thompson, Paul, additional, Thomopoulos, Sophia I., additional, Nir, Talia M., additional, Jahanshad, Neda, additional, DeCarli, Charles, additional, Knaack, Alexander, additional, Fletcher, Evan, additional, Tosun-Turgut, Duygu, additional, Chen, Stephanie Rossi, additional, Choe, Mark, additional, Crawford, Karen, additional, Yushkevich, Paul A., additional, Das, Sandhitsu, additional, Koeppe, Robert A., additional, Reiman, Eric M., additional, Chen, Kewei, additional, Mathis, Chet, additional, Landau, Susan, additional, Cairns, Nigel J., additional, Householder, Erin, additional, Franklin, Erin, additional, Bernhardt, Haley, additional, Taylor-Reinwald, Lisa, additional, Korecka, Magdalena, additional, Figurski, Michal, additional, Neu, Scott, additional, Apostolova, Liana G., additional, Shen, Li, additional, Foroud, Tatiana M., additional, Nudelman, Kelly, additional, Faber, Kelley, additional, Wilmes, Kristi, additional, Thal, Leon, additional, Silbert, Lisa C., additional, Lind, Betty, additional, Crissey, Rachel, additional, Kaye, Jeffrey A., additional, Carter, Raina, additional, Dolen, Sara, additional, Quinn, Joseph, additional, Schneider, Lon S., additional, Pawluczyk, Sonia, additional, Becerra, Mauricio, additional, Teodoro, Liberty, additional, Dagerman, Karen, additional, Spann, Bryan M., additional, Vanderswag, Helen, additional, Ziolkowski, Jaimie, additional, Heidebrink, Judith L., additional, Zbizek-Nulph, Lisa, additional, Lord, Joanne L., additional, Mason, Sara S., additional, Albers, Colleen S., additional, Knopman, David, additional, Johnson, Kris, additional, Villanueva-Meyer, Javier, additional, Pavlik, Valory, additional, Pacini, Nathaniel, additional, Lamb, Ashley, additional, Kass, Joseph S., additional, Doody, Rachelle S., additional, Shibley, Victoria, additional, Chowdhury, Munir, additional, Rountree, Susan, additional, Dang, Mimi, additional, Stern, Yaakov, additional, Honig, Lawrence S., additional, Mintz, Akiva, additional, Ances, Beau, additional, Winkfield, David, additional, Carroll, Maria, additional, Stobbs-Cucchi, Georgia, additional, Oliver, Angela, additional, Creech, Mary L., additional, Mintun, Mark A., additional, Schneider, Stacy, additional, Geldmacher, David, additional, Love, Marissa Natelson, additional, Griffith, Randall, additional, Clark, David, additional, Brockington, John, additional, Marson, Daniel, additional, Grossman, Hillel, additional, Goldstein, Martin A., additional, Greenberg, Jonathan, additional, Mitsis, Effie, additional, Shah, Raj C., additional, Lamar, Melissa, additional, Samuels, Patricia, additional, Duara, Ranjan, additional, Greig-Custo, Maria T., additional, Rodriguez, Rosemarie, additional, Albert, Marilyn, additional, Onyike, Chiadi, additional, Farrington, Leonie, additional, Rudow, Scott, additional, Brichko, Rottislav, additional, Kielb, Stephanie, additional, Smith, Amanda, additional, Raj, Balebail Ashok, additional, Fargher, Kristin, additional, Sadowski, Martin, additional, Wisniewski, Thomas, additional, Shulman, Melanie, additional, Faustin, Arline, additional, Rao, Julia, additional, Castro, Karen M., additional, Ulysse, Anaztasia, additional, Chen, Shannon, additional, Sheikh, Mohammed O., additional, Singleton-Garvin, Jamika, additional, Petrella, JeffreyR., additional, James, Olga, additional, Wong, Terence Z., additional, Borges-Neto, Salvador, additional, Karlawish, Jason H., additional, Wolk, David A., additional, Vaishnavi, Sanjeev, additional, Clark, Christopher M., additional, Arnold, Steven E., additional, Smith, Charles D., additional, Jicha, Gregory A., additional, Raslau, Flavius D., additional, Lopez, Oscar L., additional, Oakley, MaryAnn, additional, Simpson, Donna M., additional, Porsteinsson, Anton P., additional, Martin, Kim, additional, Kowalski, Nancy, additional, Keltz, Melanie, additional, Goldstein, Bonnie S., additional, Makino, Kelly M., additional, Ismail, M. Saleem, additional, Brand, Connie, additional, Thai, Gaby, additional, Pierce, Aimee, additional, Yanez, Beatriz, additional, Sosa, Elizabeth, additional, Witbracht, Megan, additional, Kelley, Brendan, additional, Nguyen, Trung, additional, Womack, Kyle, additional, Mathews, Dana, additional, Quiceno, Mary, additional, Levey, Allan I., additional, Lah, James J., additional, Hajjar, Ihab, additional, Cellar, Janet S., additional, Burns, Jeffrey M., additional, Swerdlow, Russell H., additional, Brooks, William M., additional, Silverman, Daniel H.S., additional, Kremen, Sarah, additional, Apostolova, Liana, additional, Tingus, Kathleen, additional, Lu, Po H., additional, Bartzokis, George, additional, Woo, Ellen, additional, Teng, Edmond, additional, Graff-Radford, Neill R., additional, Parfitt, Francine, additional, Poki-Walker, Kim, additional, Farlow, Martin R., additional, Hake, Ann Marie, additional, Matthews, Brandy R., additional, Brosch, Jared R., additional, Herring, Scott, additional, van, Christopher H., additional, Mecca, Adam P., additional, Good, Susan P., additional, MacAvoy, Martha G., additional, Carson, Richard E., additional, Varma, Pradeep, additional, Chertkow, Howard, additional, Vaitekunis, Susan, additional, Hosein, Chris, additional, Black, Sandra, additional, Stefanovic, Bojana, additional, Heyn, Chris (Chinthaka), additional, Robin Hsiung, Ging-Yuek, additional, Kim, Ellen, additional, Mudge, Benita, additional, Sossi, Vesna, additional, Feldman, Howard, additional, Assaly, Michele, additional, Finger, Elizabeth, additional, Pasternak, Stephen, additional, Rachinsky, Irina, additional, Kertesz, Andrew, additional, Drost, Dick, additional, Rogers, John, additional, Grant, Ian, additional, Muse, Brittanie, additional, Rogalski, Emily, additional, Robson, Jordan, additional, Mesulam, M.-Marsel, additional, Kerwin, Diana, additional, Wu, Chuang-Kuo, additional, Johnson, Nancy, additional, Lipowski, Kristine, additional, Weintraub, Sandra, additional, Bonakdarpour, Borna, additional, Pomara, Nunzio, additional, Hernando, Raymundo, additional, Sarrael, Antero, additional, Rosen, Howard J., additional, Miller, Bruce L., additional, Perry, David, additional, Turner, Raymond Scott, additional, Johnson, Kathleen, additional, Reynolds, Brigid, additional, MCCann, Kelly, additional, Poe, Jessica, additional, Sperling, Reisa A., additional, Johnson, Keith A., additional, Marshall, Gad A., additional, Yesavage, Jerome, additional, Taylor, Joy L., additional, Chao, Steven, additional, Coleman, Jaila, additional, White, Jessica D., additional, Lane, Barton, additional, Rosen, Allyson, additional, Tinklenberg, Jared, additional, Belden, Christine M., additional, Atri, Alireza, additional, Clark, Kelly A., additional, Zamrini, Edward, additional, Sabbagh, Marwan, additional, Killiany, Ronald, additional, Stern, Robert, additional, Mez, Jesse, additional, Kowall, Neil, additional, Budson, Andrew E., additional, Obisesan, Thomas O., additional, Ntekim, Oyonumo E., additional, Wolday, Saba, additional, Khan, Javed I., additional, Nwulia, Evaristus, additional, Nadarajah, Sheeba, additional, Lerner, Alan, additional, Ogrocki, Paula, additional, Tatsuoka, Curtis, additional, Fatica, Parianne, additional, Maillard, Pauline, additional, Olichney, John, additional, Carmichael, Owen, additional, Bates, Vernice, additional, Capote, Horacio, additional, Rainka, Michelle, additional, Borrie, Michael, additional, Lee, T.-Y., additional, Bartha, Dr Rob, additional, Johnson, Sterling, additional, Asthana, Sanjay, additional, Carlsson, Cynthia M., additional, Perrin, Allison, additional, Burke, Anna, additional, Scharre, Douglas W., additional, Kataki, Maria, additional, Tarawneh, Rawan, additional, Hart, David, additional, Zimmerman, Earl A., additional, Celmins, Dzintra, additional, Miller, Delwyn D., additional, BolesPonto, Laura L., additional, Smith, Karen Ekstam, additional, Koleva, Hristina, additional, Shim, Hyungsub, additional, Nam, Ki Won, additional, Schultz, Susan K., additional, Williamson, Jeff D., additional, Craft, Suzanne, additional, Cleveland, Jo, additional, Yang, Mia, additional, Sink, Kaycee M., additional, Ott, Brian R., additional, Drake, Jonathan, additional, Tremont, Geoffrey, additional, Daiello, Lori A., additional, Drake, Jonathan D., additional, Ritter, Aaron, additional, Bernick, Charles, additional, Munic, Donna, additional, O'Connelll, Abigail, additional, Mintzer, Jacobo, additional, Wiliams, Arthur, additional, Masdeu, Joseph, additional, Shi, Jiong, additional, Garcia, Angelica, additional, Newhouse, Paul, additional, Potkin, Steven, additional, Salloway, Stephen, additional, Malloy, Paul, additional, Correia, Stephen, additional, Kittur, Smita, additional, Pearlson, Godfrey D., additional, Blank, Karen, additional, Anderson, Karen, additional, Flashman, Laura A., additional, Seltzer, Marc, additional, Hynes, Mary L., additional, Santulli, Robert B., additional, Relkin, Norman, additional, Chiang, Gloria, additional, Lee, Athena, additional, Lin, Michael, additional, Ravdin, Lisa, additional, Petersen, Ron, additional, Neylan, Thomas, additional, Grafman, Jordan, additional, Danowski, Sarah, additional, Nguyen-Barrera, Catherine, additional, Hayes, Jacqueline, additional, Finley, Shannon, additional, Bernstein, Matthew, additional, Senjem, Matt, additional, Foster, Norm, additional, Kim, Sungeun, additional, Sood, Ajay, additional, Blanchard, Kimberly S., additional, Fleischman, Debra, additional, Arfanakis, Konstantinos, additional, Varon, Daniel, additional, Greig, Maria T., additional, Petrella, Jeffrey R., additional, Goldstein, Bonnie, additional, Martin, Kimberly S., additional, Reist, Christopher, additional, Sadowsky, Carl, additional, Martinez, Walter, additional, Villena, Teresa, additional, Rosen, Howard, additional, Marshall, Gad, additional, Peskind, Elaine R., additional, Petrie, Eric C., additional, Li, Gail, additional, Mackin, Scott, additional, Jimenez-Maggiora, Gustavo, additional, Drake, Erin, additional, Donohue, Mike, additional, Nelson, Craig, additional, Bickford, David, additional, Butters, Meryl, additional, Zmuda, Michelle, additional, Reyes, Denise, additional, Faber, Kelley M., additional, Nudelman, Kelly N., additional, Au, Yiu Ho, additional, Scherer, Kelly, additional, Catalinotto, Daniel, additional, Stark, Samuel, additional, Ong, Elise, additional, and Fernandez, Dariella, additional

Published
2023
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7. Common genetic loci influencing plasma homocysteine concentrations and their effect on risk of coronary artery disease

Author

van Meurs, Joyce BJ, Pare, Guillaume, Schwartz, Stephen M, Hazra, Aditi, Tanaka, Toshiko, Vermeulen, Sita H, Cotlarciuc, Ioana, Yuan, Xin, Mälarstig, Anders, Bandinelli, Stefania, Bis, Joshua C, Blom, Henk, Brown, Morris J, Chen, Constance, Chen, Yii-Der, Clarke, Robert J, Dehghan, Abbas, Erdmann, Jeanette, Ferrucci, Luigi, Hamsten, Anders, Hofman, Albert, Hunter, David J, Goel, Anuj, Johnson, Andrew D, Kathiresan, Sekar, Kampman, Ellen, Kiel, Douglas P, Kiemeney, Lambertus ALM, Chambers, John C, Kraft, Peter, Lindemans, Jan, McKnight, Barbara, Nelson, Christopher P, O’Donnell, Christopher J, Psaty, Bruce M, Ridker, Paul M, Rivadeneira, Fernando, Rose, Lynda M, Seedorf, Udo, Siscovick, David S, Schunkert, Heribert, Selhub, Jacob, Ueland, Per M, Vollenweider, Peter, Waeber, Gérard, Waterworth, Dawn M, Watkins, Hugh, Witteman, Jacqueline CM, den Heijer, Martin, Jacques, Paul, Uitterlinden, Andre G, Kooner, Jaspal S, Rader, Dan J, Reilly, Muredach P, Mooser, Vincent, Chasman, Daniel I, Samani, Nilesh J, and Ahmadi, Kourosh R

Published
2013
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9. Abstract P401: Associations Between High-density Lipoprotein Subclasses and Coronary Artery Calcification Vary by Menopausal Stage. The Study of Women's Health Across the Nation Hdl Ancillary Study

Author

El Khoudary, Samar R, primary, Nasr, Alexis, additional, Chen, Xirun, additional, Matthews, Karen A, additional, Orchard, Trevor, additional, Brooks, Maria M, additional, Billheimer, Jeff, additional, McConnell, Dan, additional, Janssen, Imke, additional, Everson-rose, Susan A, additional, Martin, Deborah, additional, and Rader, Dan, additional

Published
2020
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11. EDEM3 Modulates Plasma Triglyceride Level Through Its Regulation of LRP1 Expression

Author

Xu, Yu-Xin, primary, Peloso, Gina, additional, Nagai, Taylor, additional, Mizoguchi, Taiji, additional, Deik, Amy, additional, Bullock, Kevin, additional, Lin, Honghuang, additional, Musunuru, Kiran, additional, Yang, Qiong, additional, Vasan, Ramachandran S., additional, Gerszten, Robert E., additional, Clish, Clary, additional, Rader, Dan, additional, and Kathiresan, Sekar, additional

Published
2019
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12. A Functional, Genome-wide Evaluation of Liposensitive Yeast Identifies the “RE2 Required for Viability” (ARV1) Gene Product as a Major Component of Eukaryotic Fatty Acid Resistance

Author

Ruggles, Kelly V., primary, Garbarino, Jeanne, additional, Liu, Ying, additional, Moon, James, additional, Schneider, Kerry, additional, Henneberry, Annette, additional, Billheimer, Jeff, additional, Millar, John S., additional, Marchadier, Dawn, additional, Valasek, Mark A., additional, Joblin-Mills, Aidan, additional, Gulati, Sonia, additional, Munkacsi, Andrew B., additional, Repa, Joyce J., additional, Rader, Dan, additional, and Sturley, Stephen L., additional

Published
2014
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18. Meanwhile, Back in the Tube...

Author

Rader, Dan

Subjects
*HYPOXEMIA, *FLIGHT, *PHYSIOLOGY, *SAFETY
Abstract

Discusses the effects of hypoxia on the human body. Emergency procedure in treating a person suffering from hypoxia while in flight; Physical conditions a person experience; Changes in skin tone; Importance of oxygen.

Published
1997

19. A Functional, Genome-wide Evaluation of Liposensitive Yeast Identifies the ''ARE2 Required for Viability'' (ARV1) Gene Product as a Major Component of Eukaryotic Fatty Acid Resistance.

Author

Ruggles, Kelly V., Garbarino, Jeanne, Ying Liu, Moon, James, Schneider, Kerry, Henneberry, Annette, Billheimer, Jeff, Millar, John S., Marchadier, Dawn, Valasek, Mark A., Joblin-Mills, Aidan, Gulati, Sonia, Munkacsi, Andrew B., Repa, Joyce J., Rader, Dan, and Sturley, Stephen L.

Subjects
*LIPIDS, *OBESITY, *METABOLIC disorders, *TYPE 2 diabetes, *FATTY acids
Abstract

The toxic subcellular accumulation of lipids predisposes several human metabolic syndromes, including obesity, type 2 diabetes, and some forms of neurodegeneration. To identify pathways that prevent lipid-induced cell death, we performed a genome-wide fatty acid sensitivity screen in Saccharomyces cerevisiae. We identified 167 yeast mutants as sensitive to 0.5 mM palmitoleate, 45% of which define pathways that were conserved in humans. 63 lesions also impacted the status of the lipid droplet; however, this was not correlated to the degree of fatty acid sensitivity. The most liposensitive yeast strain arose due to deletion of the "ARE2 required for viability" (ARV1) gene, encoding an evolutionarily conserved, potential lipid transporter that localizes to the endoplasmic reticulum membrane. Down-regulation of mammalian ARV1 in MIN6 pancreatic β-cells or HEK293 cells resulted in decreased neutral lipid synthesis, increased fatty acid sensitivity, and lipoapoptosis. Conversely, elevated expression of human ARV1 in HEK293 cells or mouse liver significantly increased triglyceride mass and lipid droplet number. The ARV1-induced hepatic triglyceride accumulation was accompanied by up-regulation of DGAT1, a triglyceride synthesis gene, and the fatty acid transporter, CD36. Furthermore, ARV1 was identified as a transcriptional of the protein peroxisome proliferator-activated receptor α(PPARα), a key regulator of lipid homeostasis whose transcriptional targets include DGAT1 and CD36. These results implicate ARV1 as a protective factor in lipotoxic diseases due to modulation of fatty acid metabolism. In conclusion, a lipotoxicity-based genetic screen in a model microorganism has identified 75 human genes that may play key roles in neutral lipid metabolism and disease. [ABSTRACT FROM AUTHOR]

Published
2014
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