{'fraction_non_alphanumeric': 0.031000469704086424, 'fraction_numerical': 0.02959135744480977, 'mean_word_length': 5.805111821086262, 'pattern_counts': {'":': 0, '<': 0, '<?xml version=': 0, '>': 0, 'https://': 0, 'lorem ipsum': 0, 'www.': 0, 'xml': 0}, 'pii_count': 0, 'substrings_counts': 0, 'word_list_counts': {'cursed_substrings.json': 0, 'profanity_word_list.json': 0, 'sexual_word_list.json': 0, 'zh_pornsignals.json': 0}}
The use of bioinformatics to identify potentially damaging BK channel and palmitoylation enzyme polymorphisms as novel research targets (1138.14)

Large conductance Ca2+ and voltage‐gated potassium (BK) channels, coded for by the KCNMA1 gene, are found ubiquitously in humans and couple excitation‐contraction and stimulus‐secretion. BK channel dysfunction leads to pathophysiology affecting multiple body systems and processes (2). The BK channel undergoes palmitoylation, a post‐translational modification (PTM) that alters the trafficking, targeting and function of the protein. Palmitoylation is undertaken by a group of 23 palmitoyl‐acyl‐tranferase (PAT) enzymes coded for by the zDHHC genes. BK channel palmitoylation via PAT enzymes is crucial for BK channel function and thus has also been investigated as a novel therapeutic target. This study uses a bioinformatics approach to screen the genomic and proteomic data available for human KCNMA1 and zDHHC23, to identify and prioritise isoforms for future laboratory and clinical investigation. NCBI, Ensembl and Uniprot databases were utilised to identify: (a) splice variant information; (b) the number of non‐synonymous single‐nucleotide polymorphisms (nsSNPs); (c) nsSNP co‐location with key PTM and functional sites; (d) the damaging probability of prioritized nsSNP. Screening of KCNMA1 and zDHHC23 gene canonical proteins produced 154 and 63 unique nsSNPs respectively, with prioritisation of 13 KCNMA1 and 3 zDHHC23 nsSNP as amino acid (AA) co‐ordinates matched those of PTM residues or functionally important sites. nsSNP within 3 AA of key sites were recorded, with 64 (KCNMA1) and 22 (zDHHC23) nsSNP identified. The damaging probability of each prioritised nsSNP was assessed using SIFT and PolyPhen predictive software, with COSM196758, rs202024249, COSM920646, COSM332559 producing the highest scores. Prioritised SNPs will be investigated for functional impact in laboratory based assays. nsSNPs found to alter BK channel or PAT function will then be examined with respect to their distribution and incidence within appropriate populations and disease groups.