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Record W3184117872 · doi:10.1038/s41598-021-94048-0

Correlation between Alzheimer’s disease and type 2 diabetes using non-negative matrix factorization

2021· article· en· W3184117872 on OpenAlexafffund
Yeonwoo Chung, Hyunju Lee, Michael W. Weiner, Paul Aisen, Ronald Petersen, Cliford R. Jack, William J. Jagust, John Q. Trojanowki, Arthur W. Toga, Laurel Beckett, RobertC. Green, Andrew J. Saykin, John C. Morris, Zaven S. Khachaturian, Greg Sorensen, Maria Carrillo, Lew Kuller, Marc Raichle, Steven M. Paul, Peter J. Davies, Howard Fillit, Franz Hefti, Davie Holtzman, Marek M. Mesulam, William Z. Potter, Peter J. Snyder, Tom Montine, Ronald G. Thomas, Michael Donohue, Sarah Walter, Tamie Sather, Gus Jiminez, Archana B. Balasubramanian, Jennifer Mason, Iris Sim, Danielle Harvey, Matt A. Bernstein, Nick C. Fox, Paul M. Thompson, Norbert Schuf, Charles DeCarli, Bret Borowski, Jef Gunter, Matthew L. Senjem, Prashanthi Vemuri, David T. Jones, Kejal Kantarci, Chad Ward, Robert A. Koeppe, Norm Foster, Eric M. Reiman, Kewei Chen, Susan Landau, Nigel J. Cairns, Erin Householder, Lisa Taylor‐Reinwald, Virginia Lee, Magdalena Korecka, Michal Figurski, Karen Crawford, Scott Neu, Tatiana Foroud, Steven Potkin, Li Shen, Kelley Faber, Sungeun Kim, Lean Tha, Richard Frank, John Hsiao, Jefrey Kaye, Joseph Quinn, Lisa C. Silbert, Betty Lind, Raina Carter, Sara Dolen, Beau M. Ances, Maria Carroll, Mary L. Creech, Erin Franklin, Mark A. Mintun, Stacy Schneider, Angela Oliver, Lon S. Schneider, Sonia Pawluczyk, Mauricio Beccera, Liberty Teodoro, Bryan M. Spann, James B. Brewer, Helen Vanderswag, Adam Fleisher, Daniel Marson, Randall Grifth, David W. Clark, David Geldmacher, John Brockington, Erik D. Roberson, Marissa Natelson Love, Judith L. Heidebrink, Joanne Lord, Sara S. Mason, Colleen S. Albers, David S. Knopman, Kris Johnson, Hillel Grossman, Efe Mitsis, Raj C. Shah, Leyla deToledo‐Morrell, Rachelle S. Doody, Javier Villanueva‐Meyer, Munir Chowdhury, Susan Rountree, Mimi Dang, Ranjan Duara, Daniel Varón, Maria T. Greig, Peggy Roberts, Yaakov Stern, Lawrence S. Honig, Karen L. Bell, Marilyn Albert, Chiadi U. Onyike, Daniel D’Agostino, Stephanie Kielb, James E. Galvin, Brittany Cerbone, Christina A. Michel, Dana M. Pogorelec, Henry Rusinek, Mony J. de Leon, Lidia Glodzik, Susan De Santi, Kyle Womack, Dana Mathews, Mary Quiceno, P. Murali Doraiswamy, Jefrey R. Petrella, Salvador Borges‐Neto, Terence Z. Wong, Edward Coleman, Allan I. Levey, James J. Lah, Janet S. Cella, Jefrey M. Burns, Russell H. Swerdlow, William M. Brooks, Steven E. Arnold, Jason Karlawish, David A. Wolk, Christopher M. Clark, Liana G. Apostolova, Kathleen Tingus, Ellen Woo, Daniel Silverman, Po H. Lu, George Bartzokis, Charles D. Smith, Gregory A. Jicha, Peter Hardy, Partha Sinha, Elizabeth Oates, Gary Conrad, Neill R. Graf-Radford, Francine Parftt, Tracy Kendall, Heather Johnson, Oscar L. López, MaryAnn Oakley, Donna M. Simpson, Martin R. Farlow, Ann Marie Hake, Brandy R. Matthews, Jared R. Brosch, Scott Herring, Cynthia Hunt, Anton P. Porsteinsson, Bonnie S. Goldstein, Kim Martin, Kelly M. Makino, M. Saleem Ismail, Connie Brand, Ruth A. Mulnard, Gaby Thai, Catherine Mc-Adams-Ortiz, Christopher H. van Dyck, Richard E. Carson, Martha G. MacAvoy, Pradeep Varma, Howard Chertkow, Howard Bergman, Chris Hosein, Sandra E. Black, Bojana Stefanovic, Curtis Caldwell, Ging‐Yuek Robin Hsiung, Howard Feldman, Benita Mudge, Michele Assaly, Elizabeth Finger, Stephen Pasternack, Irina Rachisky, Dick Trost, Andrew Kertesz, Charles Bernick, Donna Munic, Kristine Lipowski, Masandra Weintraub, Borna Bonakdarpour, Diana Kerwin, Chuang‐Kuo Wu, Nancy Johnson, Carl Sadowsky, Teresa Villena, Raymond Scott Turner, Kathleen Johnson, Brigid Reynolds, Reisa A. Sperling, Keith A. Johnson, Gad Marshall, Jerome A. Yesavage, Joy L. Taylor, Barton Lane, Allyson Rosen, Jared Tinklenberg, Marwan N. Sabbagh, Christine M. Belden, Sandra A. Jacobson, Sherye A. Sirrel, Neil W. Kowall, Ronald Killiany, Andrew E. Budson, Alexander Norbash, Patricia Lynn Johnson, Thomas O. Obisesan, Saba Wolday, Joanne Allard, Alan J. Lerner, Paula Ogrocki, Curtis Tatsuoka, Parianne Fatica, Evan Fletcher, Pauline Maillard, John Olichney, Owen Carmichael, Smita Kittur, Michael Borrie, T.-Y. Lee, Robert Bartha, Sterling C. Johnson, Sanjay Asthana, Cynthia M. Carlsson, Adrian Preda, Dana Nguyen, Pierre N. Tariot, Anna Burke, Nadira Trncic, Stephanie Reeder, Vernice Bates, Horacio Capote, Michelle Rainka, Douglas W. Scharre, Maria Kataki, Anahita Adeli, Earl A. Zimmerman, Dzintra Celmins, Alice D. Brown, Godfrey D. Pearlson, Karen Blank, Karen Anderson, Laura A. Flashman, Marc Seltzer, Mary L. Hynes, Robert B. Santulli, Kaycee M. Sink, Leslie Gordineer, Jef D. Williamson, Pradeep Garg, Franklin Watkins, Brian R. Ott, Henry Querfurth, Geofrey Tremont, Stephen Salloway, Paul Malloy, Stephen Correia, Howard J. Rosen, Bruce L. Miller, David C. Perry, Jacobo Mintzer, Kenneth Spicer, David Bachman, Stephen Pasternak, Irina Rachinsky, John Rogers, Dick Drost, Nunzio Pomara, Raymundo Hernando, Antero Sarrael, Susan K. Schultz, Laura L. Boles Ponto, Hyungsub Shim, Karen Ekstam Smith, Norman Relkin, Gloria Chaing, Michael Lin, Lisa Ravdin, Amanda Smith, Balebail Ashok Raj, Kristin Fargher

Bibliographic record

VenueScientific Reports · 2021
Typearticle
Languageen
FieldBiochemistry, Genetics and Molecular Biology
TopicBioinformatics and Genomic Networks
Canadian institutionsSt Joseph's Health CareSunnybrook Health Science CentreSt Joseph's Health CentreMcGill UniversityJewish General Hospital
FundersNational Institute on AgingNational Institute of Biomedical Imaging and BioengineeringCanadian Institutes of Health ResearchUniversity of California, San DiegoGenentechRosetrees TrustNational Institutes of HealthU.S. National Library of MedicineIXICOServierEisaiKorea Health Industry Development InstituteNorthern California Institute for Research and EducationNovartis Pharmaceuticals CorporationMinistry of Science and ICT, South KoreaBiogenBioClinicaF. Hoffmann-La RocheSynarcUniversity of Southern CaliforniaMedpaceU.S. Department of DefenseEli Lilly and CompanyBristol-Myers SquibbAlzheimer's Disease Neuroimaging InitiativePennsylvania Department of HealthMeso Scale DiagnosticsAlzheimer's AssociationFoundation for the National Institutes of Health
KeywordsNon-negative matrix factorizationType 2 diabetesDiseaseCandidate geneGeneLogistic regressionCorrelationGeneticsAlzheimer's diseaseBiologyDiabetes mellitusComputational biologyMedicineMatrix decompositionInternal medicineMathematicsEndocrinology

Abstract

fetched live from OpenAlex

Alzheimer's disease (AD) is a complex and heterogeneous disease that can be affected by various genetic factors. Although the cause of AD is not yet known and there is no treatment to cure this disease, its progression can be delayed. AD has recently been recognized as a brain-specific type of diabetes called type 3 diabetes. Several studies have shown that people with type 2 diabetes (T2D) have a higher risk of developing AD. Therefore, it is important to identify subgroups of patients with AD that may be more likely to be associated with T2D. We here describe a new approach to identify the correlation between AD and T2D at the genetic level. Subgroups of AD and T2D were each generated using a non-negative matrix factorization (NMF) approach, which generated clusters containing subsets of genes and samples. In the gene cluster that was generated by conventional gene clustering method from NMF, we selected genes with significant differences in the corresponding sample cluster by Kruskal-Wallis and Dunn-test. Subsequently, we extracted differentially expressed gene (DEG) subgroups, and candidate genes with the same regulation direction can be extracted at the intersection of two disease DEG subgroups. Finally, we identified 241 candidate genes that represent common features related to both AD and T2D, and based on pathway analysis we propose that these genes play a role in the common pathological features of AD and T2D. Moreover, in the prediction of AD using logistic regression analysis with an independent AD dataset, the candidate genes obtained better prediction performance than DEGs. In conclusion, our study revealed a subgroup of patients with AD that are associated with T2D and candidate genes associated between AD and T2D, which can help in providing personalized and suitable treatments.

Fetched live from OpenAlex and de-inverted. Abstracts are not stored in this database: the inverted indexes are 8.6 GB of the frame’s 9.3 GB of text, and the host has 13 GB free.

How this classification was reachedexpand

Full frame distilled prediction

Teacher imitation

Not calibrated prevalence, not ground truth. Human validation pending. Learned from the 10,348 direct Codex labels and 10,348 direct Gemma labels. Candidate is the union of thresholded teacher heads; consensus is their intersection. These outputs are machine_predicted_unvalidated and are not human labels or direct frontier model labels.

metaresearch head score (Codex)0.000
metaresearch head score (Gemma)0.000
Version: codex-gemma-dda1882f352aValidation status: machine_predicted_unvalidated
Candidate categoriesnone
Consensus categoriesnone
DomainCandidate signal: none · Consensus signal: none
Study designCandidate signal: Bench or experimental · Consensus signal: none
GenreCandidate signal: Empirical · Consensus signal: Empirical
Teacher disagreement score0.308
Threshold uncertainty score0.343

Codex and Gemma teacher scores by category

CategoryCodexGemma
Metaresearch0.0000.000
Meta-epidemiology (narrow)0.0000.000
Meta-epidemiology (broad)0.0000.000
Bibliometrics0.0000.000
Science and technology studies0.0000.000
Scholarly communication0.0000.000
Open science0.0000.000
Research integrity0.0000.000
Insufficient payload (model declined to judge)0.0000.000

Machine scores (provisional)

The two teacher heads of the student model, read on this work. A score orders the frame for review; it never asserts a category, and the validation status ships verbatim with every row.

Baseline scores from an immature model (maturity gate not passed, 7 training rounds). Scores rank; they never assert a category.

Opus teacher head0.016
GPT teacher head0.262
Teacher spread0.246 · how far apart the two teachers sit on this one work
Validation statusscore_only:v0-immature-baseline · verbatim from the scoring run: score_only means the number may rank works, and no category label ships from it

Classification

machine, unvalidated

Machine predicted; a candidate call from one teacher head, not a consensus.

The models applied no category: nothing in the taxonomy fit this work.
Study designBench or experimental
Domainnot available
GenreEmpirical

How this classification was reached, model by model and score by score, is at the end of the page under "How this classification was reached".

Quick stats

Citations31
Published2021
Admission routes2
Has abstractyes

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