A deep learning framework for efficient pathology image analysis

P Peter Neidlinger T Tim Lenz S Sebastian Foersch C Chiara M. L. Loeffler J Jan Clusmann M Marco Gustav L Lawrence A. Shaktah R Rupert Langer B Bastian Dislich L Lisa A. Boardman A Amy J. French E Ellen L. Goode A Andrea Gsur S Stefanie Brezina M Marc J. Gunter R Robert Steinfelder H Hans-Michael Behrens C Christoph Röcken T Tabitha Harrison U Ulrike Peters (Fred Hutchinson Cancer Research Center, Seattle, WA, USA.) A Amanda I. Phipps G Giuseppe Curigliano N Nicola Fusco A Antonio Marra M Michael Hoffmeister H Hermann Brenner J Jakob Nikolas Kather

Abstract

Abstract Artificial intelligence has transformed digital pathology by enabling biomarker prediction from high-resolution whole-slide images. However, current methods are computationally inefficient, processing thousands of redundant tiles per slide and requiring complex aggregation models. We introduce EAGLE (Efficient Approach for Guided Local Examination), a deep learning framework that emulates pathologists by selectively analyzing informative regions. EAGLE combines task-agnostic tile selection with detailed feature extraction and is benchmarked against leading slide- and tile-level foundation models across 43 tasks from nine cancer types spanning morphology, biomarker prediction, treatment response and prognosis. EAGLE outperforms patch aggregation methods by up to 23% and achieves the highest overall classification performance. It processes one slide in 2.27 s, reducing computational time by more than 99% compared with existing models. This efficiency supports rapid and auditable workflows by enabling review of the exact tiles used for each prediction and reducing dependence on high-performance computing. By reliably identifying informative regions and minimizing artifacts, EAGLE provides robust and auditable outputs, supported by systematic negative controls and attention concentration analyses. Its unified embedding enables rapid slide search, integration into multi-omics pipelines and emerging clinical foundation models.

Article Details

Volume / Issue Vol. 17, Issue 1
Published July 01, 2026
ISSN 2041-1723
Publisher Nature Portfolio

Journal Info

Nature Communications

Nature Portfolio

ISSN: 2041-1723 Open Access Life Sciences

Authors (27)

P

Peter Neidlinger

T

Tim Lenz

S

Sebastian Foersch

C

Chiara M. L. Loeffler

J

Jan Clusmann

M

Marco Gustav

L

Lawrence A. Shaktah

R

Rupert Langer

B

Bastian Dislich

L

Lisa A. Boardman

A

Amy J. French

E

Ellen L. Goode

A

Andrea Gsur

S

Stefanie Brezina

M

Marc J. Gunter

R

Robert Steinfelder

H

Hans-Michael Behrens

C

Christoph Röcken

T

Tabitha Harrison

U

Ulrike Peters

Fred Hutchinson Cancer Research Center, Seattle, WA, USA.

A

Amanda I. Phipps

G

Giuseppe Curigliano

N

Nicola Fusco

A

Antonio Marra

M

Michael Hoffmeister

H

Hermann Brenner

J

Jakob Nikolas Kather