Informatics in Medicine Unlocked (Jan 2023)
In-silico evaluation of fungal and bacterial L-asparaginases allergenicity
Abstract
l-asparaginase (l-ASNase) is a vital therapeutic agent for acute lymphoblastic leukemia and is naturally produced by various organisms even though all the commercial L-ASNases are derived from bacteria that have allergic reactions mainly due to their prokaryotic origin. Since fungi are eukaryotes and their enzymes are expected to be similar to mammal proteins, the immune reactions against them are expected to be low. With this thought, this study aimed to provide insight that fungi are superior sources of l-ASNase for clinical use compared to bacteria. Aiming this, a total number of 120 sequences, 60 each from fungal and bacterial sources, were retrieved from the National Center for Biotechnology Information database. The datasets were grouped into three groups based on amino acid (aa) sequence length: 298–315, 340–355, and 375–390, each group consisting of 20 sequences. Subsequently, these sequences were analyzed using Bioinformatics tools. The comparative analysis of fungal and bacterial L-ASNases allergenicity using Algpred 2.0 showed that 32/60 (53.3 %) fungal L-ASNases and 56/60 (93.3 %) bacterial L-ASNases were predicted to be allergenic which was significantly different (p = 0.00). This was supported by AllerTOP 2.0 which predicted 23/60 fungal and 34/60 bacterial L-ASNases as allergenic. Surprisingly, the Allergome database has strengthened this result by indicating fungal L–ASNases are less allergenic (p = 0.003) compared to their bacterial counterparts which leads to conclude that l–ASNase allergenicity is correlated to its origin. Moreover, allergenicity of l-ASNase is also correlated with sequence length as predicted by Algpred 2.0, AllerTOP 2.0, and Allergome. In general, this study provided an outline of evidence that fungal L-ASNases have less allergenicity compared to their bacterial counterparts. Hence, fungi could be considered as potential sources of l-ASNase with reduced allergenicity.