A Data-Driven Approach to Construct a Molecular Map of <i>Trypanosoma cruzi</i> to Identify Drugs and Vaccine Targets
Swarsat Kaushik Nath,
Preeti Pankajakshan,
Trapti Sharma,
Priya Kumari,
Sweety Shinde,
Nikita Garg,
Kartavya Mathur,
Nevidita Arambam,
Divyank Harjani,
Manpriya Raj,
Garwit Kwatra,
Sayantan Venkatesh,
Alakto Choudhoury,
Saima Bano,
Prashansa Tayal,
Mahek Sharan,
Ruchika Arora,
Ulrich Strych,
Peter J. Hotez,
Maria Elena Bottazzi,
Kamal Rawal
Affiliations
Swarsat Kaushik Nath
Centre for Computational Biology and Bioinformatics, Amity Institute of Biotechnology, Amity University, Noida 201303, Uttar Pradesh, India
Preeti Pankajakshan
Centre for Computational Biology and Bioinformatics, Amity Institute of Biotechnology, Amity University, Noida 201303, Uttar Pradesh, India
Trapti Sharma
Centre for Computational Biology and Bioinformatics, Amity Institute of Biotechnology, Amity University, Noida 201303, Uttar Pradesh, India
Priya Kumari
Centre for Computational Biology and Bioinformatics, Amity Institute of Biotechnology, Amity University, Noida 201303, Uttar Pradesh, India
Sweety Shinde
Centre for Computational Biology and Bioinformatics, Amity Institute of Biotechnology, Amity University, Noida 201303, Uttar Pradesh, India
Nikita Garg
Centre for Computational Biology and Bioinformatics, Amity Institute of Biotechnology, Amity University, Noida 201303, Uttar Pradesh, India
Kartavya Mathur
Centre for Computational Biology and Bioinformatics, Amity Institute of Biotechnology, Amity University, Noida 201303, Uttar Pradesh, India
Nevidita Arambam
Centre for Computational Biology and Bioinformatics, Amity Institute of Biotechnology, Amity University, Noida 201303, Uttar Pradesh, India
Divyank Harjani
Centre for Computational Biology and Bioinformatics, Amity Institute of Biotechnology, Amity University, Noida 201303, Uttar Pradesh, India
Manpriya Raj
Centre for Computational Biology and Bioinformatics, Amity Institute of Biotechnology, Amity University, Noida 201303, Uttar Pradesh, India
Garwit Kwatra
Centre for Computational Biology and Bioinformatics, Amity Institute of Biotechnology, Amity University, Noida 201303, Uttar Pradesh, India
Sayantan Venkatesh
Centre for Computational Biology and Bioinformatics, Amity Institute of Biotechnology, Amity University, Noida 201303, Uttar Pradesh, India
Alakto Choudhoury
Centre for Computational Biology and Bioinformatics, Amity Institute of Biotechnology, Amity University, Noida 201303, Uttar Pradesh, India
Saima Bano
Centre for Computational Biology and Bioinformatics, Amity Institute of Biotechnology, Amity University, Noida 201303, Uttar Pradesh, India
Prashansa Tayal
Centre for Computational Biology and Bioinformatics, Amity Institute of Biotechnology, Amity University, Noida 201303, Uttar Pradesh, India
Mahek Sharan
Centre for Computational Biology and Bioinformatics, Amity Institute of Biotechnology, Amity University, Noida 201303, Uttar Pradesh, India
Ruchika Arora
Centre for Computational Biology and Bioinformatics, Amity Institute of Biotechnology, Amity University, Noida 201303, Uttar Pradesh, India
Ulrich Strych
Texas Children’s Hospital Center for Vaccine Development, Departments of Pediatrics and Molecular Virology and Microbiology, Baylor College of Medicine, Houston, TX 77030, USA
Peter J. Hotez
Texas Children’s Hospital Center for Vaccine Development, Departments of Pediatrics and Molecular Virology and Microbiology, Baylor College of Medicine, Houston, TX 77030, USA
Maria Elena Bottazzi
Texas Children’s Hospital Center for Vaccine Development, Departments of Pediatrics and Molecular Virology and Microbiology, Baylor College of Medicine, Houston, TX 77030, USA
Kamal Rawal
Centre for Computational Biology and Bioinformatics, Amity Institute of Biotechnology, Amity University, Noida 201303, Uttar Pradesh, India
Chagas disease (CD) is endemic in large parts of Central and South America, as well as in Texas and the southern regions of the United States. Successful parasites, such as the causative agent of CD, Trypanosoma cruzi have adapted to specific hosts during their phylogenesis. In this work, we have assembled an interactive network of the complex relations that occur between molecules within T. cruzi. An expert curation strategy was combined with a text-mining approach to screen 10,234 full-length research articles and over 200,000 abstracts relevant to T. cruzi. We obtained a scale-free network consisting of 1055 nodes and 874 edges, and composed of 838 proteins, 43 genes, 20 complexes, 9 RNAs, 36 simple molecules, 81 phenotypes, and 37 known pharmaceuticals. Further, we deployed an automated docking pipeline to conduct large-scale docking studies involving several thousand drugs and potential targets to identify network-based binding propensities. These experiments have revealed that the existing FDA-approved drugs benznidazole (Bz) and nifurtimox (Nf) show comparatively high binding energies to the T. cruzi network proteins (e.g., PIF1 helicase-like protein, trans-sialidase), when compared with control datasets consisting of proteins from other pathogens. We envisage this work to be of value to those interested in finding new vaccines for CD, as well as drugs against the T. cruzi parasite.
