Bioinformatics

COMPUTATIONAL PALAEOPROTEOMICS

Identification of amino acid substitutions not present in modern sequence variability, as expected in extinct organisms, can prove to be particularly challenging. In these cases, reliable options for homology searching, identification of sequence variants and amino acid substitutions, or de novo sequencing, integrated within the main search-engine would improve a lot the identification of cryptic substitutions. Finally, native integration of algorithms for blind identification of spontaneous post-translational modifications (PTMs) into the main peptide-spectrum matching (PSM) tools will allow a streamlined identification of amino acid substitutions of phylogenetic relevance. We will implement dedicated computational palaeoproteomics solutions as extensions to the established MaxQuant and Andromeda platforms. The Andromeda search engine will be further optimized to enable confident identification in such a situation. Alternatively, pre-existing de novo sequencing techniques will be further developed to be able to identify peptides and proteins independently of a sequence database. This includes clustering of single spectral de novo identifications in order to be able to confidently identify regions or domains of proteins that have sufficient MS/MS sequence coverage, and to map out their modification content. Algorithm for the search engine-driven and for the unrestricted, i.e. blind, identification of amino acid modifications will be developed for the specific challenges of ancient samples. A deep learning system will be developed and trained to be able to automatically apply domain-specific rules for the interpretation of product ion spectra. This includes special rules for the proper treatment of deamidation and other modifications in order to aid distinguishing clear cases of ancient sample-specific processes from sample preparation by-products. An expert system-informed localization score will apply this knowledge to calculate reliable localization properties for PTMs and amino acid substitutions.