Network approach to mutagenesis sheds insight on phage resistance in mycobacteria
| العنوان: | Network approach to mutagenesis sheds insight on phage resistance in mycobacteria |
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| المؤلفون: | Saptarshi Sinha, Sourabh Samaddar, Soumen Roy, Sujoy K. Das Gupta |
| المصدر: | Bioinformatics. 37:213-220 |
| بيانات النشر: | Oxford University Press (OUP), 2021. |
| سنة النشر: | 2021 |
| مصطلحات موضوعية: | Statistics and Probability, 0303 health sciences, 030306 microbiology, Computer science, Node (networking), Mutant, Mutagenesis (molecular biology technique), Network science, Computational biology, Biochemistry, Measure (mathematics), Graph, Computer Science Applications, 03 medical and health sciences, Computational Mathematics, Computational Theory and Mathematics, Interaction network, Shortest path problem, Molecular Biology, 030304 developmental biology |
| الوصف: | Motivation A rigorous yet general mathematical approach to mutagenesis, especially one capable of delivering systems-level perspectives would be invaluable. Such systems-level understanding of phage resistance is also highly desirable for phage–bacteria interactions and phage therapy research. Independently, the ability to distinguish between two graphs with a set of common or identical nodes and identify the implications thereof, is important in network science. Results Herein, we propose a measure called shortest path alteration fraction (SPAF) to compare any two networks by shortest paths, using sets. When SPAF is one, it can identify node pairs connected by at least one shortest path, which are present in either network but not both. Similarly, SPAF equalling zero identifies identical shortest paths, which are simultaneously present between a node pair in both networks. We study the utility of our measure theoretically in five diverse microbial species, to capture reported effects of well-studied mutations and predict new ones. We also scrutinize the effectiveness of our procedure through theoretical and experimental tests on Mycobacterium smegmatis mc2155 and by generating a mutant of mc2155, which is resistant to mycobacteriophage D29. This mutant of mc2155, which is resistant to D29 exhibits significant phenotypic alterations. Whole-genome sequencing identifies mutations, which cannot readily explain the observed phenotypes. Exhaustive analyses of protein–protein interaction network of the mutant and wild-type, using the machinery of topological metrics and differential networks does not yield a clear picture. However, SPAF coherently identifies pairs of proteins at the end of a subset of shortest paths, from amongst hundreds of thousands of viable shortest paths in the networks. The altered functions associated with the protein pairs are strongly correlated with the observed phenotypes. Supplementary information Supplementary data are available at Bioinformatics online. |
| تدمد: | 1367-4811 1367-4803 |
| URL الوصول: | https://explore.openaire.eu/search/publication?articleId=doi_dedup___::f48f6ff23db03653a22e313c11cf8ec0 https://doi.org/10.1093/bioinformatics/btaa1103 |
| حقوق: | OPEN |
| رقم الأكسشن: | edsair.doi.dedup.....f48f6ff23db03653a22e313c11cf8ec0 |
| قاعدة البيانات: | OpenAIRE |
| تدمد: | 13674811 13674803 |
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