Computational integration of renal histology and urinary proteomics using neural networks

Nicholas Lucarelli, Donghwan Yun, Dohyun Han, Brandon Ginley, Kyung Chul Moon, Avi Rosenberg, John Tomaszewski, Seung Seok Han, Pinaki Sarder

Research output: Chapter in Book/Report/Conference proceedingConference contributionpeer-review

1 Scopus citations

Abstract

Histological image data and molecular profiles provide context into renal condition. Often, a biopsy is drawn to diagnose or monitor a suspected kidney problem. However, molecular profiles can go beyond a pathologist's ability to see and diagnose. Using AI, we computationally incorporated urinary proteomic profiles with microstructural morphology from renal biopsy to investigate new and existing molecular links to image phenotypes. We studied whole slide images of periodic acid-Schiff stained renal biopsies from 56 DN patients matched with 2,038 proteins measured from each patient's urine. Using Seurat, we identified differentially expressed proteins in patients that developed end-stage renal disease within 2 years of biopsy. Glomeruli, globally sclerotic glomeruli, and tubules were segmented from WSI using our previously published HAIL pipeline. For each glomerulus, 315 handcrafted digital image features were measured, and for tubules, 207 features. We trained fully connected networks to predict urinary protein measurements that were differentially expressed between patients who did/ did not progress to ESRD within 2 years of biopsy. The input to this network was either glomerular or tubular histomorphological features in biopsy. Trained network weights were used as a proxy to rank which morphological features correlated most highly with specific urinary proteins. We identified significant image feature-protein pairs by ranking network weights by magnitude. We also looked at which features on average were most significant in predicting proteins. For both glomeruli and tubules, RGB color values and variance in PAS+ areas (specifically basement membrane for tubules) were, on average, more predictive of molecular profiles than other features. There is a strong connection between molecular profile and image phenotype, which can be elucidated through computational methods. These discovered links can provide insight to disease pathways, and discover new factors contributing to incidence and progression.

Original languageEnglish
Title of host publicationMedical Imaging 2022
Subtitle of host publicationDigital and Computational Pathology
EditorsJohn E. Tomaszewski, Aaron D. Ward, Richard M. Levenson
PublisherSPIE
ISBN (Electronic)9781510649538
DOIs
StatePublished - 2022
EventMedical Imaging 2022: Digital and Computational Pathology - Virtual, Online
Duration: 21 Mar 202227 Mar 2022

Publication series

NameProgress in Biomedical Optics and Imaging - Proceedings of SPIE
Volume12039
ISSN (Print)1605-7422

Conference

ConferenceMedical Imaging 2022: Digital and Computational Pathology
CityVirtual, Online
Period21/03/2227/03/22

Bibliographical note

Publisher Copyright:
© COPYRIGHT SPIE.

Keywords

  • Artificial Intelligence (AI)
  • Diabetic Nephropathy (DN)
  • Digital Pathology
  • Urinary Proteomics

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