The accumulation of large-scale drug molecule profiling datasets has paved the way to a new field of science, called chemoinformatics. Developed in silico models can serve as an efficient and cost-effective augmentation to the experimental laboratory screening approaches.
The main aim of M.Tech. Balaguru Ravikumar’s thesis entitled "Computational frameworks to aid pharmacological studies: Tools, Databases and Prediction models” was to develop novel computational methods, databases and tools for interpreting drug screening data. His doctoral dissertation will be examined on Friday, 28 February, with the permission of the Faculty of Biological and Environmental Sciences of the University of Helsinki.
Balaguru Ravikumar graduated from Jawaharlal Nehru University in New Delhi in 2013, specialising in computational and systems biology. He received a highly competitive FIMM-EMBL PhD student position and started at the rotation programme the same year. After the rotation period, he decided to start his PhD project in the computational research group of FIMM-EMBL Group Leader Tero Aittokallio. The thesis has been done in close collaboration with the FIMM High Throughput Biomedicine Unit.
– I decided to join FIMM because I found the possibility to combine computational field with working with true patient data very attractive, Balaguru tells.
In his thesis, Balaguru concentrated on developing novel computational frameworks for data analysis to facilitate extracting meaningful information from the functional drug testing datasets. Importantly, most of the computational approached developed are designed and deployed with an accompanying web-based graphic user interface. This in turn aids in the translatability of the platforms for wider user community without prior expertise in data analysis and scripting languages.
My thesis was motivated towards identifying niches and current limitations, where an effective computational framework could be utilized to complement and expedite the conventional drug discovery process.
Balaguru’s thesis consists of five already published articles, one of which is a review. Among the most widely used open-data tools and platforms Balaguru developed are C-SPADE, a tool that facilitates interactive analysis and visualization of compound screening experiments, and Drug Target Commons (DTC), one-stop resource for drug discovery and in silico model development.
In addition to the tools and databases, he also designed and implemented diverse machine learning models primarily to predict potent compound-kinase interactions and to fill the current experimental gaps in large-scale activity profiling studies.
One of the developed computational frameworks was termed Virtual Kinome Profiler. As part of the thesis projects, the applicability of this tool for compound repositioning and lead identification studies was demonstrated by predicting and experimentally validating 19 novel kinase-compound interactions.
Overall, Balaguru’s thesis work provides novel contributions to computer-aided drug discovery frameworks.
I feel that my PhD project has been a very important opportunity for me to learn how to collaborate efficiently as part of a big team with members representing different disciplines.
– I am grateful for the funding provided by the doctoral school thas has made it possible for me to participate in international conferences. I think that developing web-tools is actually more straightforward than reaching potential users. Conferences have proven to be an extremely important way to spread the word.
Balaguru has already started working at Orion Diagnostica as a software-modeling engineer supporting pharmaceutical chemists by developing and implementing computational tools. He is excited about the opportunity to learn what’s it like to work outside academia.
The public examination of Balaguru Ravikumar’s doctoral dissertation will take place on 28 February at 12 o'clock noon in the Lecture hall 3 at Biomedicum Helsinki 1, Haartmaninkatu 8. The thesis has been supervised by FIMM-EMBL Group Leader, Professor Tero Aittokallio. Reader/Associate Professor Andreas Bender, University of Cambridge will serve as the opponent and Professor Kari P Keinänen as the custos.
The dissertation is also available in an electronic form