Development of a computing platform extensible and modular for metabolomics and metagenomics analysis: innovation with the discovery of new enzymatic activities and natural products of pharmaceutical interest derived

• Grant number: 17/18922-2
• Support Opportunities: BIOTA-FAPESP Program - Young Investigators Grants
• Start date: March 01, 2019
• End date: February 29, 2024
• Field of knowledge: Health Sciences - Pharmacy - Pharmacognosy
• Principal Investigator: Ricardo Roberto da Silva
• Grantee: Ricardo Roberto da Silva
• Host Institution: Faculdade de Ciências Farmacêuticas de Ribeirão Preto (FCFRP). Universidade de São Paulo (USP). Ribeirão Preto , SP, Brazil
• Associated researchers: Norberto Peporine Lopes
• Associated scholarship(s): 22/15042-0 - Metabolome monitoring in microbial co-cultures using custom hardware and software, BP.IC; 21/08235-3 - Unraveling the evolutionary logic and structure of the marine resistome: a deep structured learning approach to discovery of evolutionary constraints, BP.DR; 21/14237-9 - Development of a web application template for creating and managing databases of natural products from local biodiversity, BP.MS; + associated scholarships 21/03368-5 - Creation of a support library for custom web applications for sphingolipids in head and neck cancer, BP.IC; 20/10351-9 - Creation of a dynamic representation library of multivariate statistics summaries using web technologies, BP.IC; 19/18378-6 - Auxiliary module for discovering chemical structures in literature: data mining, BP.IC; 19/05026-4 - Development of a computational platform extensible and modular for analysis of metabolomics and metagenomics experiments: Innovating with the discovery of new enzymatic activities and derived natural products of interest, AP.BTA.JP - associated scholarships

Abstract

The evolution in the data volume generated in modern omics experiments has led to the development of new analytical methods to explore complex multidimensional datasets. At the same time that the new experimental data creates conceptual challenges, the availability of a large volume of experimental data offers a great opportunity to apply technologies developed in other fields for big data management. This availability creates an opportunity to build a national platform for analysis and management of large datasets, exploring the potential of Brazilian biodiversity for the discovery of natural products and its pharmaceutical applications. It is estimated that approximately 60% of all drugs currently, registred have a natural product involved in its development and Brazilian biodiversity corresponds to about 20% of the world's biodiversity. Big data analysis allows the detection of correlations between sampled variables (e.g. metabolites) and the state of the system under study (e.g. healthy patient vs. diseased patient), which could not be observed with depth and detail which systems were analyzed in the past. Recently many methods for predicting biosynthetic pathways of natural products have been automated and made publicly available. Large scale gene predictions have been demonstrated with the application of large-scale super-expression of proteins combined to non-target metabolic, allowing the discovery of new enzymatic activities and new structures of metabolites. This approach is relatively simple and inexpensive, and has a great biotechnological potential. In addition to enabling the characterization of chemical diversity and its direct association to biosynthetic potential, it creates a route for biotechnological application with the cloning of genes that produce biochemical transformations of interest. The untargeted and large-scale nature of this approach allows analyzes of poorly characterized samples, such as microbial communities. The present project aims at the extension of a Galaxy platform instance for analysis of omics experiments. The analysis flow will feature original modules for ion detection optimization in non-targeted metabolomics experiments, matching the discovery of biosynthetic pathways and new structures of natural products. This infrastructure will be used to support strategic collaborations by implementing a heterologous expression platform in microorganisms. To enhance the platform's communitary use, exploring the use of multivariate statistical analysis applied to different biological systems, the present proposal foresees the integration of two FAPESP Thematic Projects linked to Biota Program. One of them providing support in mass spectrometry, coordinated by Prof. Dr. Norberto Peporine Lopes and another on bioprospecting of marine natural products coordinated by Prof. Dr. Leticia Costa Lotufo. In order to extend the project to the plant kingdom, we also started an interaction with the Project of the SPEC Program of FAPESP coordinated by Prof. Dr. Jonathan James Lloyd aimed at a large experimental study on the neglected Caatinga biome. These interactions will provide access to a diverse collection of big data that, together with the experiments proposed here, will be used to validate a platform integrating digital resources in multiple layers. This approach introduces a rational hardware management and flexible implementation of software on-demand that should create a new line of research that will benefit the research structure of the Faculdade de Ciências Farmacêuticas de Ribeirão Preto (FCFRP-USP). (AU)

Scientific publications

(12)

(References retrieved automatically from Web of Science and SciELO through information on FAPESP grants and their corresponding numbers as mentioned in the publications by the authors)

FAEDO, RAQUEL ROMAN; DA SILVA, GABRIEL; DA SILVA, RODRIGO MOREIRA; USHIDA, TATIANE RESENDE; DA SILVA, RICARDO ROBERTO; LACCHINI, RICCARDO; MATOS, LEANDRO LUONGO; KOWALSKI, LUIZ PAULO; LOPES, NOBERTO PEPORINE; LEOPOLDINO, ANDREIA MACHADO. Sphingolipids signature in plasma and tissue as diagnostic and prognostic tools in oral squamous cell carcinoma. BIOCHIMICA ET BIOPHYSICA ACTA-MOLECULAR AND CELL BIOLOGY OF LIPIDS, v. 1867, n. 1, JAN 2022. (17/18922-2, 18/17480-9, 16/19103-2, 19/05026-4, 18/03278-3)

KONG, YA-SHUAI; REN, HONG-YU; LIU, RUI; DA SILVA, RICARDO R.; AKSENOV, ALEXANDER A.; V. MELNIK, ALEXEY; ZHAO, MING; LE, MIAO-MIAO; REN, ZHI-WEI; XU, FENG-QING; et al. Microbial and Nonvolatile Chemical Diversities of Chinese Dark Teas Are Differed by Latitude and Pile Fermentation. Journal of Agricultural and Food Chemistry, v. 70, n. 18, p. 14-pg., 2022-05-11. (19/05026-4, 17/18922-2)

TAMASCO, GUSTAVO; KUMAR, MANISH; ZENGLER, KARSTEN; SILVA-ROCHA, RAFAEL; DA SILVA, RICARDO ROBERTO. ChiMera: an easy to use pipeline for bacterial genome based metabolic network reconstruction, evaluation and visualization. BMC Bioinformatics, v. 23, n. 1, p. 13-pg., 2022-11-30. (17/18922-2, 19/05026-4, 19/15675-0)

DOS SANTOS, ANCELY F.; INAGUE, ALEX; ARINI, GABRIEL S.; TERRA, LETICIA F.; WAILEMANN, ROSANGELA A. M.; PIMENTEL, ANDRE C.; YOSHINAGA, MARCOS Y.; SILVA, RICARDO R.; SEVERINO, DIVINOMAR; DE ALMEIDA, DARIA RAQUEL Q.; et al. Distinct photo-oxidation-induced cell death pathways lead to selective killing of human breast cancer cells. CELL DEATH & DISEASE, v. 11, n. 12, DEC 14 2020. (19/09517-2, 17/13804-1, 19/05026-4, 16/04676-7, 17/23914-9, 17/18922-2, 17/03618-6, 15/02654-3, 13/07937-8)

DE ALMEIDA, DARIA R. Q.; DOS SANTOS, ANCELY F.; WAILEMANN, ROSANGELA A. M.; TERRA, LETICIA F.; GOMES, VINICIUS M.; ARINI, GABRIEL S.; BERTOLDI, ESTER R. M.; REIS, EDUARDO M.; BAPTISTA, MAURICIO S.; LABRIOLA, LETICIA. Necroptosis activation is associated with greater methylene blue-photodynamic therapy-induced cytotoxicity in human pancreatic ductal adenocarcinoma cells. PHOTOCHEMICAL & PHOTOBIOLOGICAL SCIENCES, v. N/A, p. 16-pg., 2022-12-10. (17/18922-2, 17/13804-1, 19/05026-4, 15/02654-3, 16/04676-7, 17/03618-6, 19/09517-2, 13/07937-8)

DA COSTA, BRUNO RUIZ BRANDAO; DA SILVA, RICARDO ROBERTO; BIGAO, VITOR LUIZ CALEFFO PIVA; PERIA, FERNANDA MARIS; DE MARTINIS, BRUNO SPINOSA. Hybrid volatilomics in cancer diagnosis by HS-GC-FID fingerprinting. JOURNAL OF BREATH RESEARCH, v. 17, n. 2, p. 15-pg., 2023-04-01. (19/05026-4, 20/02207-5, 17/18922-2)

BIN KANG, KYO; WOO, SUNMIN; ERNST, MADELEINE; VAN DER HOOFT, JUSTIN J. J.; NOTHIAS, LOUIS-FELIX; DA SILVA, RICARDO R.; DORRESTEIN, PIETER C.; SUNG, SANG HYUN; LEE, MINA. Assessing specialized metabolite diversity of Alnus species by a digitized LC-MS/MS data analysis workflow. Phytochemistry, v. 173, MAY 2020. (17/18922-2, 19/05026-4)

KAZANDJIAN, T. D.; PETRAS, D.; ROBINSON, S. D.; VAN THIEL, J.; GREENE, H. W.; ARBUCKLE, K.; BARLOW, A.; CARTER, D. A.; WOUTERS, R. M.; WHITELEY, G.; et al. Convergent evolution of pain-inducing defensive venom components in spitting cobras. Science, v. 371, n. 6527, p. 386+, JAN 22 2021. (19/05026-4, 17/18922-2)

MCAVOY, ANDREW C.; JAIYESIMI, OLAKUNLE; THREATT, PAXTON H.; SELADI, TYLER; GOLDBERG, JOANNA B.; DA SILVA, RICARDO R.; GARG, NEHA. Differences in Cystic Fibrosis-Associated Burkholderia spp. Bacteria Metabolomes after Exposure to the Antibiotic Trimethoprim. ACS INFECTIOUS DISEASES, v. 6, n. 5, p. 1154-1168, MAY 8 2020. (17/18922-2, 19/05026-4)

CARABALLO-RODRIGUEZ, ANDRES MAURICIO; PUCKETT, SARA P.; KYLE, KATHLEEN E.; PETRAS, DANIEL; DA SILVA, RICARDO; NOTHIAS, LOUIS-FELIX; ERNST, MADELEINE; VAN DER HOOFT, JUSTIN J. J.; TRIPATHI, ANUPRIYA; WANG, MINGXUN; et al. Chemical Gradients of Plant Substrates in an Atta texana Fungus Garden. MSYSTEMS, v. 6, n. 4, AUG 2021. (17/18922-2, 19/05026-4)

LEO, TIAGO F.; WANG, MINGXUN; DA SILVA, RICARDO; GUREVICH, ALEXEY; BAUERMEISTER, ANELIZE; GOMES, PAULO WENDER P.; BREJNROD, ASKER; GLUKHOV, EVGENIA; ARON, ALLEGRA T.; LOUWEN, JORIS J. R.; et al. NPOmix: A machine learning classifier to connect mass spectrometry fragmentation data to biosynthetic gene clusters. PNAS NEXUS, v. 1, n. 5, p. 15-pg., 2022-11-01. (17/18922-2, 19/05026-4)

BORELLI, TIAGO CABRAL; ARINI, GABRIEL SANTOS; FEITOSA, LUIS G. P.; DORRESTEIN, PIETER C.; LOPES, NORBERTO PEPORINE; DA SILVA, RICARDO R.. Improving annotation propagation on molecular networks through random walks: introducing ChemWalker. Bioinformatics, v. 39, n. 3, p. 2-pg., 2023-03-01. (21/08235-3, 20/02207-5, 17/18922-2, 19/05026-4, 21/10401-9)