Sarath Chandra Janga, associate professor of bioinformatics and data science in the Department of BioHealth Informatics at the IU School of Informatics and Computing at IUPUI, was awarded a $299,698 NSF Early-Concept Grants for Exploratory Research (EAGER) grant. EAGER funding is used to support exploratory work in its early stages on untested, but potentially transformative, research ideas or approaches.
Janga’s project, “EAGER: Algorithmic frameworks and resources for mapping RNA modifications from single molecule direct RNA-sequencing data,” will enable discovery of all the messenger RNA molecules expressed from the genes of an organism and the code that allow RNA and related proteins to operate in real time at a single-molecule resolution. Little is known about the molecular players that are involved in the numerous steps that govern expression patterns, including localization, splicing, stability, and folded structure of the RNA.
Ribonucleic acid, or RNA, is one of the three major biological macromolecules essential for all known forms of life. A central tenet of molecular biology states that the flow of genetic information in a cell is from DNA through RNA to proteins: “DNA makes RNA makes protein”.
Janga and his lab propose to detect, identify, and quantify RNA modifications using the Oxford Nanopore platform, and results will be analyzed for robustness in precision and accuracy. Experiments will utilize synthetic calibration as well as newly-developed algorithms.
Janga is also Co-PI on a Software Hardware Foundation (SHF) grant awarded in tandem by the National Science Foundation, titled “Automated Algorithm/Hardware Co-design for Accelerating Nanopore Base-calling,” with Principal Investigator Lei Jiang, assistant professor in the IUB department of Intelligent Systems Engineering.
Significantly, nanopore genome sequencing is becoming the cornerstone to enabling personalized medicine, global food security, and wildlife conservation, says Janga. “Base-calling,” the process of assigning bases to signal peaks generated by the gene sequencer, is time consuming. Although current approaches reduce computing overhead, they increase systematic errors, which results in lower accuracy in base-calling. Jiang and Janga propose to develop a novel algorithm and hardware co-design methodology to make base-calling more power efficient, scalable, and accessible.
Janga says that improvements to nanopore base-calling at both at the DNA and RNA levels, supported by these two grants from the NSF, “could offer on-demand rapid genome and transcriptome sequencing solutions, thus making real-time, in-home diagnostic tool kits for several infectious and complex diseases a reality.” He believes that overcoming base-calling limitations of the current computational frameworks — coupled with developments in nanopore sequencing — would pave the path for day-to-day use of sequencing technology to realize the dream of in-home clinical care in the 21st century.
This material is based upon work supported by the National Science Foundation under Grant No. 1940422 and Grant No. 1908992. Any opinions, findings, and conclusions or recommendations expressed in this material are those of the author(s) and do not necessarily reflect the views of NSF.