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Abstract
Pathologists use visual classification to assess patient kidney biopsy samples when diagnosing the underlying cause of kidney disease. However, the assessment is qualitative, or semi-quantitative at best, and reproducibility is challenging. To discover previously unknown features which predict patient outcomes and overcome substantial interobserver variability, we developed an unsupervised bag-of-words model. Our study applied to the C-PROBE cohort of patients with chronic kidney disease (CKD). 107,471 histopathology images were obtained from 161 biopsy cores and identified important morphological features in biopsy tissue that are highly predictive of the presence of CKD both at the time of biopsy and in one year. To evaluate the performance of our model, we estimated the AUC and its 95% confidence interval. We show that this method is reliable and reproducible and can achieve 0.93 AUC at predicting glomerular filtration rate at the time of biopsy as well as predicting a loss of function at one year. Additionally, with this method, we ranked the identified morphological features according to their importance as diagnostic markers for chronic kidney disease. In this study, we have demonstrated the feasibility of using an unsupervised machine learning method without human input in order to predict the level of kidney function in CKD. The results from our study indicate that the visual dictionary, or visual image pattern, obtained from unsupervised machine learning can predict outcomes using machine-derived values that correspond to both known and unknown clinically relevant features.
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1 University of Michigan, Department of Computational Medicine and Bioinformatics, Ann Arbor, USA (GRID:grid.214458.e) (ISNI:0000000086837370)
2 University of Michigan, Department of Internal Medicine, Nephrology, Ann Arbor, USA (GRID:grid.214458.e) (ISNI:0000000086837370)
3 University of Michigan, Department of Pediatrics, Pediatric Nephrology, Ann Arbor, USA (GRID:grid.214458.e) (ISNI:0000000086837370)
4 St. Clair Nephrology Research, Department of Internal Medicine, Nephrology, Detroit, USA (GRID:grid.214458.e)
5 Wayne State University, Department of Internal Medicine, Nephrology, Detroit, USA (GRID:grid.254444.7) (ISNI:0000 0001 1456 7807)
6 Cleveland Clinic, Department of Internal Medicine, Nephrology, Cleveland, USA (GRID:grid.239578.2) (ISNI:0000 0001 0675 4725)
7 Levine Children’s Hospital, Department of Pediatrics, Pediatric Nephrology, Charlotte, USA (GRID:grid.415907.e) (ISNI:0000 0004 0411 7193)
8 Department of JH Stroger Hospital, Department of Internal Medicine, Nephrology, Chicago, USA (GRID:grid.415907.e)
9 University of Michigan, Department of Pathology, Ann Arbor, USA (GRID:grid.214458.e) (ISNI:0000000086837370)
10 University of Michigan, Department of Computational Medicine and Bioinformatics, Ann Arbor, USA (GRID:grid.214458.e) (ISNI:0000000086837370); University of Michigan, Department of Biostatistics, Ann Arbor, USA (GRID:grid.214458.e) (ISNI:0000000086837370); University of Michigan, Department of Radiation Oncology, Ann Arbor, USA (GRID:grid.214458.e) (ISNI:0000000086837370); University of Michigan, Department of Biomedical Engineering, Ann Arbor, USA (GRID:grid.214458.e) (ISNI:0000000086837370)