Computational comparative analysis of human and swine leukocyte antigens (HLA/SLA) and its implications in xenotransplantation

• Grant number: 20/08726-4
• Support Opportunities: Scholarships in Brazil - Post-Doctoral
• Start date: September 01, 2020
• End date: August 31, 2022
• Field of knowledge: Physical Sciences and Mathematics - Computer Science
• Principal Investigator: Jorge Elias Kalil Filho
• Grantee: Deibs Barbosa
• Host Institution: Faculdade de Medicina (FM). Universidade de São Paulo (USP). São Paulo , SP, Brazil
• Company: Universidade de São Paulo (USP). Faculdade de Medicina (FM)
• CNAE: Atividades de atenção à saúde humana não especificadas anteriormente
• CNAE: Atividades de atenção à saúde humana não especificadas anteriormente
• Associated research grant: 18/14275-5 - National production of genetically modified pigs for organ xenotransplantation in humans, AP.PITE

Abstract

Brazil has an extensive system for solid organs transplantation, occupyingthe second place in absolute number of procedures. However, there is an increasingdemand for transplantation. In this context, xenotransplantation (transplantation carried outbetween different species) arises as an alternative. Among potential animal donors areswine (Sus scrofa). Objective: the project proposes to analyze repertoires of HLA/SLA leukocyte antigen alleles through a computational approach, evaluating their diversity and clarifying the possible implications for the success of xenotransplantation. Methods: reads from the leukocyte antigen genes amplicons will be pre-processed, trimming and discarding low quality sequences. The selected reads will be aligned to the human or porcine reference genome, haplotypes will be identified from this mapping and compared with genes deposited in the IPD-IMGT/HLA database. A phylogenetic reconstruction will be performed from the multiple alignment of the DNA sequences for each gene. The aminoacid sequences of the alleles belonging to the same group will be used to search for shared epitopic regions, including the polymorphic residues. Expected results: at the completion of the project, it is expected an accurate and highly reproducible pipeline for genotyping HLA/SLA genes by NGS sequencing and a list of HLA/SLA alleles with sharedepitopes. (AU)