Data integration to identify biological markers of neurodevelopmental disorders

• Grant number: 18/18560-6
• Support Opportunities: Research Projects - Thematic Grants
• Start date: October 01, 2019
• End date: September 30, 2025
• Field of knowledge: Health Sciences - Medicine - Psychiatry
• Principal Investigator: Helena Paula Brentani
• Grantee: Helena Paula Brentani
• Host Institution: Faculdade de Medicina (FM). Universidade de São Paulo (USP). São Paulo , SP, Brazil
• City of the host institution: São Paulo
• Principal investigators: Carlos Alberto de Bragança Pereira ; David Corrêa Martins Junior
• Associated researchers: Alexandra Valéria Maria Brentani ; ALOISIO SOUZA FELIPE DA SILVA ; Eurípedes Constantino Miguel Filho ; Gisele Rodrigues Gouveia ; Guilherme Vanoni Polanczyk ; Ricardo Zorzetto Nicoliello Vêncio ; Rossana Pulcineli Vieira Francisco ; Sandra Josefina Ferraz Ellero Grisi ; Sérgio Nery Simões
• Associated scholarship(s): 21/00485-0 - Predicting neurodevelopment by stressors exposures through statistical models: an integrative approach, BP.DD; 21/00607-9 - Em estudo piloto usando uma amostra de 100 crianças da coorte (ROC), buscamos componentes principais (PC) a partir de diferentes medidas de exposição materna ao estresse gestacional, BP.PD; 20/16376-3 - Determination of polygenic risk to characterize exposure to gestational stress, BP.DD; + associated scholarships 20/15590-1 - Polygenic risk scores and epigenetic risk markers data integration for neurodevelopment prediction from children in psychosocial vulnerability situations, BP.PD; 21/00230-2 - Evaluation of placental exosomes of pregnants from a randomized clinical trial to test an intensive home visit program effectiveness, BP.IC; 20/15382-0 - Telomere length evaluation of pregnant women from a randomized clinical trial to test the effectiveness of an intensive home visit program, BP.IC; 20/14360-2 - Evaluation of the OGT protein expression level in placenta tissues in relation to the embryo sex, BP.IC; 20/10217-0 - Biological sample collection, processing, storage and transport for Modules I and II subprojects of the Thematic Project, BP.TT; 20/02766-4 - Biological sample collection, processing, storage and transport for modules I and II subprojects of the thematic project, BP.TT - associated scholarships

Abstract

Neurodevelopmental disorders are polygenic and multifactorial. Besides the genetic component, evidences from animal and human studies indicate that environmental adversities and / or psychosocial stresses experienced early in life can trigger epigenetic changes that may influence brain plasticity, neural circuit connectivity and functioning. These changes may affect the adequate development of cognitive functions, emotional reactivity and sociability, increasing the risk for presenting neurodevelopmental disorders. The crucial role of the epigenetic machinery in the biological incorporation of exposure to stress in early life has been demonstrated in several animal models. These were exposed to different prenatal and / or postnatal stresses such as nutrition, drugs, inadequate maternal care, separation of the mother-child binomial and social enrichment / isolation, suggesting epigenetic molecular markers of risk. However, most of these studies are performed with exposure to specific environmental factors, such as nicotine use during pregnancy. That is, these studies disregard that an individual is normally exposed to several environmental stressors and that each individual responds individually to them. Another important point is that the sexes respond differently to stress exposure, thus adding an additional level of variability to the possible neurodevelopmental trajectories. Polygenic risk scores (PRSs) have contributed to a better understanding of these disorders, but these only consider the effect of genetic variations. It is necessary to search for methods to integrate PRSs with epigenetic risk markers, sex of the concept and the temporal effect of exposure to different types of stress to identify susceptibility markers associated with risk phenotypes for neurodevelopmental disorders. This project proposes a multidisciplinary approach using Systemic Biology tools and machine learning to integrate complex data, that is, of different natures. Specifically, we aim to achieve the following objectives: 1) to integrate environmental exposure data, and show that a multivariate stress construct approach is associated with individual biomarkers of stress reactivity by improving the prediction of phenotypes associated with neurodevelopmental trajectories; 2) to integrate data of gene expression, epigenetics, sex of the concept and environmental exposure to develop a biological model to explain differences in susceptibility between sexes for neurodevelopmental disorders; 3) to integrate polygenic risk scores data with environmental exposure and epigenetic molecular markers of risk to characterize genomic areas, that could be evaluated improving the prediction of phenotypes associated with neurodevelopmental trajectories. The completion of these objectives will provide new methodologies for complex data integration, molecular targeting and identification of potential preventive measures related to the development of neurodevelopmental disorders. (AU)

Scientific publications

(17)

(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)

SIQUEIRA, RODRIGO A. DE O.; STEFANES, MARCO A.; ROZANTE, LUIZ C. S.; MARTINS-JR, DAVID C.; DE SOUZA, JORGE E. S.; ARAUJO, ELOI; GERVASI, O; MURGANTE, B; MISRA, S; GARAU, C; et al. Multi-GPU Approach for Large-Scale Multiple Sequence Alignment. COMPUTATIONAL SCIENCE AND ITS APPLICATIONS, ICCSA 2021, PT I, v. 12949, p. 16-pg., 2021-01-01. (18/21934-5, 18/18560-6)

TOVAR, CARLOS R. P.; MARTINS-, DAVID C., JR.; ROZANTE, LUIZ C. S.; ARAUJO, ELOI; IEEE COMP SOC. A Method for Computing Attractor Fields in Coupled Boolean Networks. 2022 IEEE 22ND INTERNATIONAL CONFERENCE ON BIOINFORMATICS AND BIOENGINEERING (BIBE 2022), v. N/A, p. 6-pg., 2022-01-01. (18/18560-6, 18/21934-5)

DUARTE, RODRIGO R. R.; BRENTANI, HELENA; POWELL, TIMOTHY R.. Ditching candidate gene association studies: lessons from psychiatric genetics. Revista Brasileira de Psiquiatria, v. 43, n. 3, p. 342-344, MAY-JUN 2021. (18/18560-6)

SANTOS, MARCUS VINICIUS C.; FELTRIN, ARTHUR S. S.; COSTA-AMARAL, ISABELE C. C.; TEIXEIRA, LILIANE R. R.; PERINI, JAMILA A. A.; MARTINS JR, DAVID C. C.; LARENTIS, ARIANE L. L.. Network Analysis of Biomarkers Associated with Occupational Exposure to Benzene and Malathion. INTERNATIONAL JOURNAL OF MOLECULAR SCIENCES, v. 24, n. 11, p. 18-pg., 2023-05-28. (18/18560-6, 18/21934-5)

EUCLYDES, VERONICA; BRAGA, CAIO I. S.; GOUVEIA, GISELE; MARTINEZ, RAQUEL C. R.; CAMILO, CAROLINE; SIMOES, SERGIO N.; MARTINS-JR, DAVID C.; FRACOLLI, LISLAINE; ARGEU, ADRIANA; FERRARO, ALEXANDRE; et al. Maternal immune response during pregnancy and neurodevelopmental outcomes: A longitudinal approach. BRAIN, BEHAVIOR, & IMMUNITY - HEALTH, v. 40, p. 11-pg., 2024-08-05. (18/18560-6, 20/16376-3, 23/01343-0, 16/22455-8, 18/21934-5, 20/15590-1, 21/00485-0)

BONINI, RODRIGO CESAR; MARTINS-, DAVID CORREA, JR.. Gene Networks Inference by Reinforcement Learning. ADVANCES IN BIOINFORMATICS AND COMPUTATIONAL BIOLOGY, BSB 2023, v. 13954, p. 12-pg., 2023-01-01. (18/21934-5, 18/18560-6)

GOMES, CATARINA S.; EUCLYDES, VERONICA; CAMILO, CAROLINE; GOUVEIA, GISELE; BRENTANI, HELENA. Multi-polygenic risk score approach to neurodevelopment-associated trait prediction in a high risk admixed cohort. European Journal of Human Genetics, v. 32, p. 2-pg., 2024-12-01. (18/18560-6)

CAMILO, CAROLINE; VIEIRA, LUANA MARTOS; GOUVEIA, GISELE RODRIGUES; TORREZAN, ARLETI CARAMORI; PEIXOTO, ANDREA; EUCLYDES, VERONICA; FRANCISCO, ROSSANA PULCINELI VIEIRA; BRENTANI, ALEXANDRA; FELIPE-SILVA, ALOISIO; BRENTANI, HELENA. Innovative approach for the qualitative-quantitative assessment of neurodevelopment biomarkers research in placenta tissue using immunohistochemistry digital image analysis. BIOLOGY METHODS & PROTOCOLS, v. 10, n. 1, p. 12-pg., 2025-01-01. (21/00607-9, 18/18560-6)

BARREIRO, RODRIGO A. S.; DE ALMEIDA, TATIANA F.; GOMES, CATARINA; MONFARDINI, FREDERICO; DE FARIAS, ALLYSSON A.; TUNES, GABRIELA C.; DE SOUZA, GABRIEL M.; DUIM, ETIENNE; DE SA CORREIA, JAQUELINE; COELHO, ANTONIO V. CAMPOS; et al. Assessing the Risk Stratification of Breast Cancer Polygenic Risk Scores in a Brazilian Cohort. JOURNAL OF MOLECULAR DIAGNOSTICS, v. 26, n. 9, p. 7-pg., 2024-08-23. (18/18560-6, 14/50931-3, 13/08028-1, 20/16376-3, 14/50649-6)

WILEY, KYLE S.; CAMILO, CAROLINE; GOUVEIA, GISELE; EUCLYDES, VERONICA; PANTER-BRICK, CATHERINE; MATIJASEVICH, ALICIA; FERRARO, ALEXANDRE ARCHANJO; FRACOLLI, LISLAINE APARECIDA; CHIESA, ANNA MARIA; MIGUEL, EURIPEDES CONSTANTINO; et al. Maternal distress, DNA methylation, and fetal programing of stress physiology in Brazilian mother-infant pairs. DEVELOPMENTAL PSYCHOBIOLOGY, v. 65, n. 1, p. 16-pg., 2023-01-01. (16/22455-8, 18/18560-6)

FEITOSA, RAYSSA M. M. W.; PRIETO-OLIVEIRA, PAULA; BRENTANI, HELENA; MACHADO-LIMA, ARIANE. MicroRNA target prediction tools for animals: Where we are at and where we are going to-A systematic review. COMPUTATIONAL BIOLOGY AND CHEMISTRY, v. 100, p. 14-pg., 2022-07-31. (18/18560-6, 20/01992-0)

ROZANTE, LUIZ C. S.; TOVAR, CARLOS R. P.; MARTINS-, DAVID C., JR.; DE CAMARGO, RAPHAEL Y.; ARANTES, LUCIANA; SENS, PIERRE. Efficient Computation of Attractor Fields in Coupled Boolean Networks. COMPUTATIONAL SCIENCE AND ITS APPLICATIONS-ICCSA 2025, PT I, v. 15648, p. 19-pg., 2025-01-01. (18/18560-6, 18/21934-5)

EUCLYDES, VERONICA; GOMES, CATARINA; GOUVEIA, GISELE; GASTALDI, VINICIUS DAGUANO; FELTRIN, ARTHUR SANT'ANNA; CAMILO, CAROLINE; VIEIRA, ROSSANA PULCINELI; FELIPE-SILVA, ALOISIO; GRISI, SANDRA; FINK, GUNTHER; et al. Gestational age acceleration is associated with epigenetic biomarkers of prenatal physiologic stress exposure. CLINICAL EPIGENETICS, v. 14, n. 1, p. 10-pg., 2022-12-01. (18/18560-6)

EUCLYDES, VERONICA L. V.; GASTALDI, VINICIUS D.; FELTRIN, ARTHUR S.; HOFFMAN, DANIEL J.; GOUVEIA, GISELE; COGO, HUGO; FELIPE-SILVA, ALOISIO; VIEIRA, ROSSANA P.; MIGUEL, EURIPEDES C.; POLANCZYK, GUILHERME, V; et al. DNA methylation mediates a randomized controlled trial home-visiting intervention during pregnancy and the Bayley infant's cognitive scores at 12 months of age. JOURNAL OF DEVELOPMENTAL ORIGINS OF HEALTH AND DISEASE, v. 13, n. 5, p. 10-pg., 2022-03-08. (18/18560-6)

KESWANI, DISHA; MARSZALEK, MIKOLAJ; WICIK, ZOFIA; EYILETEN, CEREN; NOWAK, ANNA; SIMOES, SERGIO; MARTINS, DAVID; KLOS, KRZYSZTOF; WLODARCZYK, WOJCIECH; ASSINGER, ALICE; et al. Changes of ACE-2 related-miR-200b-3p expression over time are a predictive factor of long hospitalization for COVID-19: in silico, machine learning and validation analysis. Journal of Pharmacology and Experimental Therapeutics, v. 385, p. 2-pg., 2023-06-01. (18/18560-6, 18/21934-5)

EYILETEN, CEREN; WICIK, ZOFIA; SIMOES, SERGIO N.; MARTINS-JR, DAVID C.; KLOS, KRZYSZTOF; WLODARCZYK, WOJCIECH; ASSINGER, ALICE; SOLDACKI, DARIUSZ; CHCIALOWSKI, ANDRZEJ; SILLER-MATULA, JOLANTA M.; et al. Thrombosis-related circulating miR-16-5p is associated with disease severity in patients hospitalised for COVID-19. RNA BIOLOGY, v. 19, n. 1, p. 17-pg., 2022-12-31. (18/18560-6, 18/21934-5)

TIETZE, ETHAN; BARBOSA, ANDRE ROCHA; ARAUJO, BRUNO; EUCLYDES, VERONICA; SPIEGELBERG, BAILEY; CHO, HYEON JIN; LEE, YONG KYU; WANG, YANHONG; MCCORD, ALEJANDRA; LORENZETTI, ALAN; et al. Human archetypal pluripotent stem cells differentiate into trophoblast stem cells via endogenous BMP5/7 induction without transitioning through naive state. SCIENTIFIC REPORTS, v. 14, n. 1, p. 15-pg., 2024-02-08. (18/18560-6)