Interpretation of the features of a linear regression model for predicting the survival time of the amyotrophic lateral sclerosis patients with mutated SOD1
Nikolay Alemasov1, Alexandr Shcherbakov2, Vladimir Timofeev3, Vladimir Ivanisenko4
1The Federal Research Center Institute of Cytology and Genetics, The Siberian Branch of the Russian Academy of Sciences, 630090, Prospekt Lavrentyeva 10, Novosibirsk, Russia, alemasov@bionet.nsc.ru
2Novosibirsk State Technical University, pr. Karla Marksa 20, Novosibirsk, 630073, Russia, aleksandr.serbakov@yandex.ru
3Novosibirsk State Technical University, pr. Karla Marksa 20, Novosibirsk, 630073, Russia, v.timofeev@corp.nstu.ru
4The Federal Research Center Institute of Cytology and Genetics, The Siberian Branch of the Russian Academy of Sciences, 630090, Prospekt Lavrentyeva 10, Novosibirsk, Russia, salix@bionet.nsc.ru
Amyotrophic lateral sclerosis (ALS) is an incurable neurodegenerative disease characterised by the inevitable degeneration of central and peripheral motor neurons. Aggregation of mutant SOD1 is one of the molecular mechanisms underlying the onset of the disease. There are a number of regression models designed to predict the survival of patients based on an analysis of experimental data on thermostability, heterodimerization energy, and changes in the hydrophobicity of SOD1 mutants. Previously, we proposed regression models linking the change in the stability of hydrogen bonds in mutant SOD1 calculated using molecular dynamics with patients’ survival time. In this work, we developed an approach to the interpretation of features of linear regression models with the aim of a deeper understanding of the structural effects of mutations in the SOD1 protein. The approach suggested was based on the principal component analysis and over-representation of features including the sequence position of amino acid residues forming the hydrogen bonds detected within a range of the structural elements of the SOD1. This study can help one to deduce important structural regions in the protein which could be further targeted by small chemical compounds.