Proteomics-Based Machine Learning Approach as an Alternative to Conventional Biomarkers for Differential Diagnosis of Chronic Kidney Diseases

International Journal of Molecular Sciences

Zoran Minic¹  MaximV. Berezovski¹  SvetlanaA. Varygina²  SofiaL. Glizer²  IrinaA. Ler²  MariaL. Rossovskaya²  MarinaM. Petrova³  TatianaN. Zamay⁴  AnnaS. Kichkailo⁴  YuryE. Glazyrin⁴  DmitryV. Veprintsev⁵ 

[1] Department of Chemistry and Biomolecular Sciences, University of Ottawa, Ottawa, ON K1N6N5, Canada;Department of Nephrology, Krasnoyarsk Interdistrict Clinical Hospital of Emergency Medical Care Named after N.S. Karpovich, 660062 Krasnoyarsk, Russia;Faculty of Medicine, Krasnoyarsk State Medical University Named after Prof. V.F. Voyno-Yasenetsky, 660022 Krasnoyarsk, Russia;Laboratory for Biomolecular and Medical Technologies, Krasnoyarsk State Medical University Named after Prof. V.F. Voyno-Yasenetsky, 660022 Krasnoyarsk, Russia;Laboratory for Digital Controlled Drugs and Theranostics, Federal Research Center “Krasnoyarsk Science Center of the Siberian Branch of the Russian Academy of Science”, 660036 Krasnoyarsk, Russia;

关键词: chronic kidney disease;    machine learning;    differential diagnosis;    proteomics;    mass spectrometry;    label-free quantification;   

DOI  :  10.3390/ijms21134802

来源: DOAJ

【 摘 要 】

Diabetic nephropathy, hypertension, and glomerulonephritis are the most common causes of chronic kidney diseases (CKD). Since CKD of various origins may not become apparent until kidney function is significantly impaired, a differential diagnosis and an appropriate treatment are needed at the very early stages. Conventional biomarkers may not have sufficient separation capabilities, while a full-proteomic approach may be used for these purposes. In the current study, several machine learning algorithms were examined for the differential diagnosis of CKD of three origins. The tested dataset was based on whole proteomic data obtained after the mass spectrometric analysis of plasma and urine samples of 34 CKD patients and the use of label-free quantification approach. The k-nearest-neighbors algorithm showed the possibility of separation of a healthy group from renal patients in general by proteomics data of plasma with high confidence (97.8%). This algorithm has also be proven to be the best of the three tested for distinguishing the groups of patients with diabetic nephropathy and glomerulonephritis according to proteomics data of plasma (96.3% of correct decisions). The group of hypertensive nephropathy could not be reliably separated according to plasma data, whereas analysis of entire proteomics data of urine did not allow differentiating the three diseases. Nevertheless, the group of hypertensive nephropathy was reliably separated from all other renal patients using the k-nearest-neighbors classifier “one against all” with 100% of accuracy by urine proteome data. The tested algorithms show good abilities to differentiate the various groups across proteomic data sets, which may help to avoid invasive intervention for the verification of the glomerulonephritis subtypes, as well as to differentiate hypertensive and diabetic nephropathy in the early stages based not on individual biomarkers, but on the whole proteomic composition of urine and blood.

【 授权许可】

Unknown