Evidence map›Paper›PMID 42146619›Full record

ArticlebioRxiv : the preprint server for biology2026

Weak supervision of H&E slides reveals systems-level biology and functional states that govern therapeutic resistance.

Tiago Goncalves, Dagoberto Pulido, Carmen M Perrino, Thanpisit Lomphithak, Mason Cleveland, Adrian V Dalca, Elizabeth Gerstner, Jason Hipp, Jay Patel, Bruce Rosen and 15 more

Abstract readPreprint
PubMed Full text at PMC Publisher
In one paragraph

Article in bioRxiv : the preprint server for biology, 2026. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Not yet cited in PubMed.

0numbers the graph read from it
0cells of the map it votes in
0citing papers in PubMed
–field-weighted citation impact
1 · What the graph read from it

What it found

Each row is one number read from the abstract, on the scale the paper reported it, with its interval. Left of the dashed line favours the treatment, right favours the comparator. Under each row is the sentence it came from. New to these charts? A ten-minute tutorial.

The abstract states no effect estimate the extractor could read, or names no intervention and outcome on the map, so this paper lights no cell and moves no belief. It is still indexed, cited and linked below.

2 · The registry

The trial behind it

Trials whose registry record cites this paper, or whose number appears in the abstract. A trial that started after this paper was published is citing it as background, not reporting it.

Neither the registry nor the abstract names a trial number. If this is a trial report, that itself is worth knowing.

3 · Its place in the literature

Who cites it

0 citing papers in PubMed.

No citing paper in PubMed yet.

4 · The record

Corrections and comments

PubMed lists nothing against this paper. Absence here is not a guarantee, only a check that was made.

5 · Who and what money

Authors and funding

25 authors.

Tiago GoncalvesINESC TEC, Faculdade de Engenharia, Universidade do Porto, Rua Dr. Roberto Frias, 4200-465 Porto, Portugal.
Dagoberto PulidoAthinoula A. Martinos Center for Biomedical Imaging, Massachusetts General Hospital, Harvard Medical School; Boston, MA.
Carmen M PerrinoAthinoula A. Martinos Center for Biomedical Imaging, Massachusetts General Hospital, Harvard Medical School; Boston, MA.
Thanpisit LomphithakDepartment of Pathology, Massachusetts General Hospital, Harvard Medical School; Boston, MA.
Mason ClevelandAthinoula A. Martinos Center for Biomedical Imaging, Massachusetts General Hospital, Harvard Medical School; Boston, MA.
Adrian V DalcaAthinoula A. Martinos Center for Biomedical Imaging, Massachusetts General Hospital, Harvard Medical School; Boston, MA.
Elizabeth GerstnerAthinoula A. Martinos Center for Biomedical Imaging, Massachusetts General Hospital, Harvard Medical School; Boston, MA.
Jason HippAthinoula A. Martinos Center for Biomedical Imaging, Massachusetts General Hospital, Harvard Medical School; Boston, MA.
Jay PatelAthinoula A. Martinos Center for Biomedical Imaging, Massachusetts General Hospital, Harvard Medical School; Boston, MA.
Bruce RosenAthinoula A. Martinos Center for Biomedical Imaging, Massachusetts General Hospital, Harvard Medical School; Boston, MA.
Sahussapont Joseph SirintrapunDepartment of Pathology, Massachusetts General Hospital, Harvard Medical School; Boston, MA.
Seth A WanderMassachusetts General Hospital Cancer Center, Harvard Medical School; Boston, MA.
Anil ParwaniDepartment of Pathology, The Ohio State University; Columbus, OH.
Gary TozbikianDepartment of Pathology, The Ohio State University; Columbus, OH.
M Khalid Khan NiaziDepartment of Pathology, The Ohio State University; Columbus, OH.
Jaime CardosoINESC TEC, Faculdade de Engenharia, Universidade do Porto, Rua Dr. Roberto Frias, 4200-465 Porto, Portugal.
Jane BrockAmerican Society of Clinical Pathology; Chicago, IL.
Valentina ZanfagninDepartment of Pathology, Massachusetts General Hospital, Harvard Medical School; Boston, MA.
Francesca GazzanigaDepartment of Pathology, Massachusetts General Hospital, Harvard Medical School; Boston, MA.
A John IafrateDepartment of Pathology, Massachusetts General Hospital, Harvard Medical School; Boston, MA.
Keith T FlahertyMassachusetts General Hospital Cancer Center, Harvard Medical School; Boston, MA.
Dennis C SgroiDepartment of Pathology, Massachusetts General Hospital, Harvard Medical School; Boston, MA.
John V GuttagComputer Science and Artificial Intelligence Laboratory (CSAIL), Department of Computer Science, Massachusetts Institute of Technology; Cambridge, MA.
Christopher P BridgeAthinoula A. Martinos Center for Biomedical Imaging, Massachusetts General Hospital, Harvard Medical School; Boston, MA.
Albert E KimAthinoula A. Martinos Center for Biomedical Imaging, Massachusetts General Hospital, Harvard Medical School; Boston, MA.

Funding

Training Program in Nervous System TumorsK12CA090354 · NCI · MASSACHUSETTS GENERAL HOSPITAL · PI PLOTKIN, SCOTT R · 2001 to 2025
$16.3M
Enhancing precision medicine for brain metastases using interpretable and integrative deep learningK08EB037077 · NIBIB · MASSACHUSETTS GENERAL HOSPITAL · PI Albert Kim · 2025 to 2026
$388k
NCI NIH HHS K12 CA090354NIBIB NIH HHS K08 EB037077
6 · The paper itself

Abstract

Precision oncology lacks scalable tools to assess, at the patient level, systems-level tumor microenvironment (TME) programs driving therapeutic resistance. To address this gap, we trained a weakly-supervised deep learning model, using routine H&E slides as input, to derive quantitative activity for therapeutically-relevant TME phenotypes, spanning immune, metabolic, and tumor cell-intrinsic programs. Using 3111 breast cancer H&E WSIs with matched bulk transcriptomics, our model accurately infers these biological states (AUROC>0.80; PCC>0.64). Validation spanned three levels: (i) tissue-matched multiplexed immunofluorescence, showing concordance between inferred functional states and immune cell fractions (p=0.006-0.106), (ii) blinded reader assessments, confirming localization of phenotype-specific morphology (p<3×10

Identifiers

PMID42146619
PMCPMC13174459

What OpenQuestion holds

Textmetadata
LicenceCC BY-NC-ND
Read underepoch 390

Registered trials

None linked

Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the OpenQuestion graph.