P091 Typeloader for windows: Automated full length submission of novel alleles

Abstract

Aim Many of the alleles submitted to the IPD-IMGT/HLA and IPD-KIR databases are restricted to the coding sequence or even, for HLA, to the exons encoding the antigen recognition domain. This impedes the establishment of long-read-based genotyping technologies. It is desirable that novel alleles are characterized and submitted in full length, and that known alleles are extended to cover the complete gene sequence. However, the manual annotation and submission of full-length sequences to the IPD-IMGT/HLA and ENA databases is a time-consuming and error-prone task. In 2016, we developed and published TypeLoader, a tool that takes the full-length sequence of a novel HLA allele in FASTA format as input, automatically annotates it, and creates all files necessary for submission. This reduced the manual effort for submission by over 95%. It was implemented as a web application to run on a Linux server and has been used at the DKMS Life Science Lab to successfully submit more than 1000 novel HLA alleles. Methods To enable a more widespread use of TypeLoader by other labs, we have adapted the tool to make it available as a Windows standalone application. We replaced the server-dependent web form with a convenient GUI (graphical user interface) using Python3 and PyQt5, which support most common operating systems. An internal SQLite database was added to store a wide range of metadata about each allele, which are accessible via the GUI. As a further improvement, TypeLoader now automatically detects null alleles generated by premature stop codons or frameshift mutations, and features enhanced integration with ENA’s automated submission API. TypeLoader also implements experimental support for annotation and submission of KIR alleles. Results The new TypeLoader can easily be used on standard PCs without dependencies on other software. With the added internal database, TypeLoader can be used as a lab’s central information platform on their full-length sequences meant for submission. Conclusions We hope that the increased convenience and scope of TypeLoader will foster the submission of more full-length sequences to the IPD-IMGT/HLA and IPD-KIR databases, ultimately promoting the widespread use of full-length sequencing for genotyping of both HLA and KIR.