Phenotypic and prognostic insights through unbiased self-supervised learning on kidney histology

Abstract

Deep learning methods for image segmentation and classification in histopathology generally utilize supervised learning, relying on manually created labels for model development. Here, we applied a self-supervised framework to characterize kidney histology without the use of pathologist annotations, training on whole slide images to identify histomorphological phenotype clusters (HPCs) and create slide-level vector representations. HPCs developed in the training set were visually consistent when transferred to five diverse internal and external validation sets (1,421 WSIs in total). Specific HPCs were reproducibly associated with slide-level pathologist quantifications, such as interstitial fibrosis (AUC = 0.83). Additionally, hierarchical clustering of tissue patterns revealed patient groups related to kidney function and genotype, and specific HPCs predicted longitudinal kidney function decline. Overall, we demonstrated the translational application of a self-supervised framework to summarize distinct kidney tissue patterns with phenotypic and prognostic relevance.

Competing Interest Statement

Aristotelis Tsirigos is a cofounder of Imagenomix.

Clinical Protocols

https://github.com/AdalbertoCq/Histomorphological-Phenotype-Learning

Funding Statement

This was an NIH-funded study.

Author Declarations

I confirm all relevant ethical guidelines have been followed, and any necessary IRB and/or ethics committee approvals have been obtained.

Yes

The details of the IRB/oversight body that provided approval or exemption for the research described are given below:

Ethics committee/IRB of the University of Pennsylvania gave ethical approval for this work. Ethics committee/IRB of Johns Hopkins University gave ethical approval for this work.

I confirm that all necessary patient/participant consent has been obtained and the appropriate institutional forms have been archived, and that any patient/participant/sample identifiers included were not known to anyone (e.g., hospital staff, patients or participants themselves) outside the research group so cannot be used to identify individuals.

Yes

I understand that all clinical trials and any other prospective interventional studies must be registered with an ICMJE-approved registry, such as ClinicalTrials.gov. I confirm that any such study reported in the manuscript has been registered and the trial registration ID is provided (note: if posting a prospective study registered retrospectively, please provide a statement in the trial ID field explaining why the study was not registered in advance).

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I have followed all appropriate research reporting guidelines, such as any relevant EQUATOR Network research reporting checklist(s) and other pertinent material, if applicable.

Yes

Data Availability

Access to training data (whole slide images) used in the present study may be available upon request. The HPL pipeline can be replicated using the following GitHub repository - https://github.com/AdalbertoCq/Histomorphological-Phenotype-Learning. Models from the current study trained on kidney tissue tiles of 5X, 10X, and 20X magnification are available here - https://github.com/AdalbertoCq/Histomorphological-Phenotype-Learning/blob/master/README.md#other-pretrained-models.

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