PMID- 32606026 OWN - NLM STAT- PubMed-not-MEDLINE LR - 20240329 IS - 2379-5077 (Print) IS - 2379-5077 (Electronic) IS - 2379-5077 (Linking) VI - 5 IP - 3 DP - 2020 Jun 30 TI - Metabolomics and Machine Learning Approaches Combined in Pursuit for More Accurate Paracoccidioidomycosis Diagnoses. LID - 10.1128/mSystems.00258-20 [doi] LID - e00258-20 AB - Brazil and many other Latin American countries are areas of endemicity for different neglected diseases, and the fungal infection paracoccidioidomycosis (PCM) is one of them. Among the clinical manifestations, pneumopathy associated with skin and mucosal lesions is the most frequent. PCM definitive diagnosis depends on yeast microscopic visualization and immunological tests, but both present ambiguous results and difficulty in differentiating PCM from other fungal infections. This research has employed metabolomics analysis through high-resolution mass spectrometry to identify PCM biomarkers in serum samples in order to improve diagnosis for this debilitating disease. To upgrade the biomarker selection, machine learning approaches, using Random Forest classifiers, were combined with metabolomics data analysis. The proposed combination of these two analytical methods resulted in the identification of a set of 19 PCM biomarkers that show accuracy of 97.1%, specificity of 100%, and sensitivity of 94.1%. The obtained results are promising and present great potential to improve PCM definitive diagnosis and adequate pharmacological treatment, reducing the incidence of PCM sequelae and resulting in a better quality of life.IMPORTANCE Paracoccidioidomycosis (PCM) is a fungal infection typically found in Latin American countries, especially in Brazil. The identification of this disease is based on techniques that may fail sometimes. Intending to improve PCM detection in patient samples, this study used the combination of two of the newest technologies, artificial intelligence and metabolomics. This combination allowed PCM detection, independently of disease form, through identification of a set of molecules present in patients' blood. The great difference in this research was the ability to detect disease with better confidence than the routine methods employed today. Another important point is that among the molecules, it was possible to identify some indicators of contamination and other infection that might worsen patients' condition. Thus, the present work shows a great potential to improve PCM diagnosis and even disease management, considering the possibility to identify concomitant harmful factors. CI - Copyright (c) 2020 Lima et al. FAU - Lima, Estela de Oliveira AU - Lima EO AUID- ORCID: 0000-0003-0479-0364 AD - Department of Internal Medicine, Botucatu Medical School, Sao Paulo State University, Botucatu, SP, Brazil. AD - Innovare Biomarkers Laboratory, School of Pharmaceutical Sciences, University of Campinas, Campinas, SP, Brazil. FAU - Navarro, Luiz Claudio AU - Navarro LC AUID- ORCID: 0000-0002-8041-8743 AD - RECOD Laboratory, Institute of Computing, University of Campinas, Campinas, SP, Brazil. FAU - Morishita, Karen Noda AU - Morishita KN AD - Innovare Biomarkers Laboratory, School of Pharmaceutical Sciences, University of Campinas, Campinas, SP, Brazil. FAU - Kamikawa, Camila Mika AU - Kamikawa CM AD - Laboratory of Mycosis Immunodiagnosis-Immunology Section, Adolfo Lutz Institute, Sao Paulo, SP, Brazil. FAU - Rodrigues, Rafael Gustavo Martins AU - Rodrigues RGM AD - Innovare Biomarkers Laboratory, School of Pharmaceutical Sciences, University of Campinas, Campinas, SP, Brazil. FAU - Dabaja, Mohamed Ziad AU - Dabaja MZ AD - Innovare Biomarkers Laboratory, School of Pharmaceutical Sciences, University of Campinas, Campinas, SP, Brazil. FAU - de Oliveira, Diogo Noin AU - de Oliveira DN AD - Innovare Biomarkers Laboratory, School of Pharmaceutical Sciences, University of Campinas, Campinas, SP, Brazil. FAU - Delafiori, Jeany AU - Delafiori J AD - Innovare Biomarkers Laboratory, School of Pharmaceutical Sciences, University of Campinas, Campinas, SP, Brazil. FAU - Dias-Audibert, Flavia Luisa AU - Dias-Audibert FL AD - Innovare Biomarkers Laboratory, School of Pharmaceutical Sciences, University of Campinas, Campinas, SP, Brazil. FAU - Ribeiro, Marta da Silva AU - Ribeiro MDS AD - Innovare Biomarkers Laboratory, School of Pharmaceutical Sciences, University of Campinas, Campinas, SP, Brazil. FAU - Vicentini, Adriana Pardini AU - Vicentini AP AD - Laboratory of Mycosis Immunodiagnosis-Immunology Section, Adolfo Lutz Institute, Sao Paulo, SP, Brazil. FAU - Rocha, Anderson AU - Rocha A AUID- ORCID: 0000-0002-4236-8212 AD - RECOD Laboratory, Institute of Computing, University of Campinas, Campinas, SP, Brazil anderson.rocha@ic.unicamp.br rrc@unicamp.br. FAU - Catharino, Rodrigo Ramos AU - Catharino RR AD - Innovare Biomarkers Laboratory, School of Pharmaceutical Sciences, University of Campinas, Campinas, SP, Brazil anderson.rocha@ic.unicamp.br rrc@unicamp.br. LA - eng PT - Journal Article DEP - 20200630 PL - United States TA - mSystems JT - mSystems JID - 101680636 PMC - PMC7329323 OTO - NOTNLM OT - artificial intelligence OT - diagnosis OT - metabolomics OT - paracoccidioidomycosis EDAT- 2020/07/02 06:00 MHDA- 2020/07/02 06:01 PMCR- 2020/06/30 CRDT- 2020/07/02 06:00 PHST- 2020/07/02 06:00 [entrez] PHST- 2020/07/02 06:00 [pubmed] PHST- 2020/07/02 06:01 [medline] PHST- 2020/06/30 00:00 [pmc-release] AID - 5/3/e00258-20 [pii] AID - mSystems00258-20 [pii] AID - 10.1128/mSystems.00258-20 [doi] PST - epublish SO - mSystems. 2020 Jun 30;5(3):e00258-20. doi: 10.1128/mSystems.00258-20.