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Record W4416595726 · doi:10.1038/s41598-025-25400-x

Challenges and best practices when using ComBAT to harmonize diffusion MRI data

2025· article· en· W4416595726 on OpenAlexafffund
Pierre‐Marc Jodoin, Manon Edde, Gabriel Girard, Félix Dumais, Guillaume Theaud, Matthieu Dumont, Jean-Christophe Houde, Yoan David, Maxime Descoteaux, Michael W. Weiner, Paul Aisen, Ronald Petersen, Clifford R. Jack, William Jagust, Susan Landau, Leslie M. Shaw, Edward B. Lee, Arthur W. Toga, Laurel Beckett, Danielle Harvey, Robert C. Green, Andrew J. Saykin, Kwangsik Nho, Richard J. Perrin, Duygu Tosun, Erin Drake, Tom Montine, Cat Conti, Rachel L. Nosheny, Diana Truran‐Sacrey, Juliet Fockler, Melanie J. Miller, Catherine Conti, Winnie Kwang, Chengshi Jin, Miriam T. Ashford, Derek Flenniken, Adrienne Kormos, Michael Rafii, Rema Raman, Gustavo Jiménez, Michael Donohue, Jennifer Salazar, Andrea Fidell, Virginia Boatwright, Justin Robison, Caileigh Zimmerman, Yuliana Cabrera, Sarah Walter, Taylor Clanton, Elizabeth Shaffer, Caitlin Webb, Lindsey Hergesheimer, Stephanie R. Rainey‐Smith, Sheila Ogwang, Olusegun Adegoke, Payam Mahboubi, Jeremy Pizzola, Cecily Jenkins, Joel P. Felmlee, Nick C. Fox, Paul M. Thompson, Charles DeCarli, Arvin Forghanian-Arani, Bret Borowski, Calvin Reyes, Caitie Hedberg, Chad Ward, Christopher G. Schwarz, Denise Reyes, Jeff Gunter, John Moore-Weiss, Kejal Kantarci, Leonard Matoush, Matthew L. Senjem, Prashanthi Vemuri, Robert W. Reid, Ian G. Malone, Sophia I. Thomopoulos, Talia M. Nir, Neda Jahanshad, Alexander Knaack, Evan Fletcher, Duygu Tosun, Stephanie Rossi Chen, Mark Choe, Karen Crawford, Paul A. Yushkevich, Sandhitsu R. Das, Naomi Saito, Kedir Adem Hussen, Hannatu Amaza, Mai Seng Thao, Matt Glittenberg, Isabella Hoang, Joe Strong, Trinity Weisensel, Fabiola Magana, Lisa Thomas, Kaori Kubo Germano, Sandra Talavera, Vanessa Guzmán, Adeyinka Ajayi, Joseph Di Benedetto, Shaniya Parkins, Omobolanle Ayo, Victor L. Villemagne, Brian J. Lopresti, Robert A. Koeppe, Gil D. Rabinovici, John C. Morris, Erin Franklin, Nigel J. Cairns, Lisa Taylor‐Reinwald, Virginia M.‐Y. Lee, Magdalena Korecka, Magdalena Brylska, Yang Wan, John Q. Trojanowki, Scott Neu, Tatiana Foroud, Taeho Jo, Shannon L. Risacher, Hannah Craft, Liana G. Apostolova, Kelly Nudelman, Kelley Faber, ZoA Potter, Kaci Lacy, Rima Kaddurah-Daouk, Li Shen, David N. Soleimani‐Meigooni, Renaud La Joie, Konstantinos Chiotis, Maison Abu Raya, Agathe Vrillon, Charles Windon, Julien Lagarde, Jason Karlawish, Emily A. Largent, Kristin Harkins, Joshua D. Grill, Zaven Kachaturian, R.T. Frank, Peter J. Snyder, Neil Buckholtz, John Hsiao, Laurie Ryan, Susan Molchan, Marı́a C. Carrillo, William Z. Potter, Héctor Alfredo Baptista González, Carole Ho, Jonathan Jackson, Eliezer Masliah, Donna Masterman, Nina Silverberg

Bibliographic record

VenueScientific Reports · 2025
Typearticle
Languageen
FieldMedicine
TopicAdvanced Neuroimaging Techniques and Applications
Canadian institutionsDouglas Mental Health University InstituteQ & T ResearchUniversité de Sherbrooke
FundersNational Institute on AgingCanadian Institutes of Health ResearchNational Institutes of HealthGenentechIXICOH. Lundbeck A/SServierMitacsEisaiQuébec Consortium for Drug DiscoveryUniversity of Southern CaliforniaUniversité de SherbrookeNorthern California Institute for Research and EducationBioClinicaNatural Sciences and Engineering Research Council of CanadaBiogenPfizerNovartis Pharmaceuticals CorporationU.S. Department of DefenseEli Lilly and CompanyBristol-Myers SquibbAlzheimer's Disease Neuroimaging InitiativeMeso Scale DiagnosticsAlzheimer's Association
KeywordsBest practiceConsistency (knowledge bases)NormativeMultiplicative functionSet (abstract data type)Population

Abstract

fetched live from OpenAlex

Over the years, ComBAT has become the standard method for harmonizing MRI-derived measurements, with its ability to compensate for site-related additive and multiplicative biases while preserving biological variability. However, ComBAT relies on a set of assumptions that, when violated, can result in flawed harmonization. In this paper, we thoroughly review ComBAT's mathematical foundation, outlining these assumptions, and exploring their implications for the demographic composition necessary for optimal results. Through a series of experiments involving a slightly modified version of ComBAT called Pairwise-ComBAT tailored for normative modeling applications, we assess the impact of various population characteristics, including population size, age distribution, the absence of certain covariates, and the magnitude of additive and multiplicative factors. Based on these experiments, we present five essential recommendations that should be carefully considered to enhance consistency and supporting reproducibility, two essential factors for open science, collaborative research, and real-life clinical deployment.

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 machine prediction

Teacher imitation

Not calibrated prevalence, not ground truth. Human validation pending. The Gemma side is a direct model label for every work in the frame, read from the title-only record. The Codex side is a classifier learned from the 10,348 direct Codex labels and calibrated to design-weighted sample rates; fields without enough sample support carry no Codex call. Candidate is the union of the two sides; consensus is their intersection. These outputs are machine_predicted_unvalidated and are not human labels.

metaresearch head score (Codex)0.300
metaresearch head score (Gemma)0.560
Version: metacan-v3-hybrid-931329e0061cValidation status: machine_predicted_unvalidated
Candidate categoriesMetaresearch
Consensus categoriesnone
DomainCandidate signal: none · Consensus signal: none
Study designCandidate signal: Bench or experimental · Consensus signal: none
GenreCandidate signal: Methods · Consensus signal: Methods
Teacher disagreement score0.300
Threshold uncertainty score0.863

Distilled classifier scores by category (both heads)

CategoryCodexGemma
Metaresearch0.3000.560
Meta-epidemiology (narrow)0.0020.002
Meta-epidemiology (broad)0.0030.002
Bibliometrics0.0040.004
Science and technology studies0.0030.008
Scholarly communication0.0160.015
Open science0.0100.012
Research integrity0.0050.008
Insufficient payload (model declined to judge)0.0050.005

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 head0.357
GPT teacher head0.459
Teacher spread0.102 · 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 source (direct Gemma or distilled Codex), not a consensus.

Study designBench or experimental
Domainnot available
GenreMethods

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

Citations3
Published2025
Admission routes2
Has abstractyes

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