Project Title: Error Correction for the Code of Life in A New Era of Genome Editing

Partnering Institutions and Investigators: Wichita State University, Ali Eslami (PI)

Funding Agency: Flossie E. West Memorial Foundation

Total Funded Amount: $25,000

Project Duration: May 1, 2016 - April 30, 2017

Abstract: All cancers are caused by errors (mutations) in the DNA sequence that cannot be detected or corrected by the body's repair mechanisms. A similar problem is faced in telecommunications when sequences of information are transmitted over a noisy channel, introducing multiple random errors. To overcome this problem, redundant bits are added to each sequence before transmission which will help correct the errors later in the receiver. This is called “Error Correction Coding” (ECC), a well-established area in communications which started in 1948 and has been perfected over time. There are immense functional similarities between the body cell's error correction mechanisms and the error correction techniques used in telecommunications. This research exploits these similarities and combines statistical methods with the powerful toolbox of algebraic error control coding to understand and then improve the body's repair mechanisms which hold the key to treating cancer and other genetic diseases. The three components of algebraic error correction are the encoder, channel, and decoder. Similarly, genetic encoder, channel, and decoder are defined in this proposal. A probabilistic model is first derived for the genetic channel through applying statistical inference to the available data of DNA mutations across the spectrum of human cancer types. Then the genetic decoder which is in charge of correcting the DNA errors is analyzed. In this approach, the decoder is divided into two components: “DNA repair mechanisms” and the “gene interactions network” which activates such mechanisms. Two very effective analytical tools are borrowed from coding theory, namely message passing and density evolution, and applied to study the global and local error correction mechanisms in the cells. The two tasks above provide the fundamental knowledge of how error correction is carried out in the cells. Given this knowledge, a systematic approach is proposed to use genome editing techniques more effectively. Particularly, target genes are identified in cancer cells to be knocked out of the DNA for the purpose of making the cells vulnerable to a particular drug.