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Record W4415731737 · doi:10.1038/s43856-026-01558-x

Interpretable Multiple Instance Learning for Hematologic Diagnosis from Peripheral Blood Smears

2025· preprint· en· W4415731737 on OpenAlexaff
Siddharth Singi, Shenghuan Sun, Zhanghan Yin, R. C. GUPTA, Dylan C. Webb, Khawaja Hasan Bilal, Deepika Dilip, Linlin Wang, Neeraj Kumar, Nicholas Sanchez, Jacob Cleaves, B. M. FRIED, Ethan Yan, Ali Kamali, Argho Sarkar, Allyne Manzo, Jeeyeon Baik, Irem Isgor, Cesar Colorado-Jimenez, Anthony B. Cardillo, Leonardo Boiocchi, Aijazuddin Syed, David Kim, Brie Kezlarian-Sachs, Maly Fenelus, Alexander Chan, Mariko Yabe, Samuel I. McCash, Menglei Zhu, Simon Mantha, Orly Ardon, Lauren McVoy, Wenbin Xiao, Mikhail Roshal, Oscar Lin, Ahmet Doǧan, Iain Carmichael, Chad Vanderbilt, Gregory M. Goldgof

Bibliographic record

VenueCommunications Medicine · 2025
Typepreprint
Languageen
FieldComputer Science
TopicDigital Imaging for Blood Diseases
Canadian institutionsUniversity of Alberta
FundersNational Cancer InstituteNational Institutes of HealthMemorial Sloan-Kettering Cancer Center
KeywordsInterpretabilityEncoderPattern recognition (psychology)Feature (linguistics)Function (biology)Pipeline (software)Softmax functionPeripheral blood

Abstract

fetched live from OpenAlex

Accurate diagnosis of hematologic malignancies from peripheral blood smears (PBSs) requires integrating cellular morphology and composition across hundreds of white blood cells. Existing approaches primarily automate single-cell classification and do not provide whole-slide diagnostic predictions. We present a full network that utilizes a highly performative cell-based encoder (DeepHeme) for feature extraction paired with our weakly supervised framework using attention-based multiple instance learning (MIL) that we call CAREMIL (Cell AggRegation, Explainable, Multiple Instance Learning). Upon evaluating various popular image encoders and MIL architectures, the combination of DeepHeme and CAREMIL is the best performing pipeline on our disease classification task. CAREMIL proves to be a robust aggregation function that outperforms the most commonly used slide level aggregation function (gated multiple instance learning) across several encoder types. The greatest improvements in performance gain with CAREMIL is observed when using out-of-domain encoders, including an encoder trained on ImageNet and leading open-source pathology foundational models (UNI2 and Virchow2). CAREMIL plus DeepHeme achieves the highest diagnostic performance across acute leukemia (AML), myelodysplastic syndromes (MDS), and hairy cell leukemia (HCL) (AUROCs 0.999, 0.891, and 0.945, respectively), and identifies AML disease even in cases with minimal or absent circulating blasts. Attention values assigned by CAREMIL highlight diagnostically relevant cells and reveal disease-specific morphometric signatures, enabling biological interpretability and case-level insight. CAREMIL remains robust to misclassified cell types by the cell image encoder and does not require explicit cell-level supervision. These findings position CAREMIL as an effective and interpretable multiple instance learning framework for hematologic slide diagnosis, with potential to extend to bone marrow aspirates, cytology, and other liquid biopsy specimens, and to support a broader shift toward quantitative, morphology-informed diagnostics in hematology.

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)0.003
Version: codex-gemma-dda1882f352aValidation status: machine_predicted_unvalidated
Candidate categoriesMeta-epidemiology (narrow), Open science
Consensus categoriesnone
DomainCandidate signal: none · Consensus signal: none
Study designCandidate signal: Simulation or modeling · Consensus signal: none
GenreCandidate signal: Methods · Consensus signal: none
Teacher disagreement score0.814
Threshold uncertainty score1.000

Codex and Gemma teacher scores by category

CategoryCodexGemma
Metaresearch0.0000.003
Meta-epidemiology (narrow)0.0000.000
Meta-epidemiology (broad)0.0010.000
Bibliometrics0.0000.000
Science and technology studies0.0000.000
Scholarly communication0.0000.000
Open science0.0070.006
Research integrity0.0000.001
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 head0.048
GPT teacher head0.323
Teacher spread0.275 · 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.

Study designSimulation or modeling
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

Citations0
Published2025
Admission routes1
Has abstractyes

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