Kaist Researchers Develop Universal Technology To Restore Altered Gene Networks

Previously, investigation connected controlling cistron networks has been carried retired based connected a azygous stimulus-response of cells. More recently, studies person been projected to precisely analyse analyzable cistron networks to place power targets. A KAIST investigation squad has succeeded successful processing a cosmopolitan exertion that identifies cistron power targets successful altered cellular cistron networks and restores them. This accomplishment is expected to beryllium wide applied to caller anticancer therapies specified arsenic crab reversibility, supplier development, precision medicine, and reprogramming for compartment therapy.

KAIST (President Kwang Hyung Lee) announced connected nan 28th of August that Professor Kwang-Hyun Cho's investigation squad from nan Department of Bio and Brain Engineering has developed a exertion to systematically place cistron power targets that tin reconstruct nan altered stimulus-response patterns of cells to normal by utilizing an algebraic approach. The algebraic attack expresses cistron networks arsenic mathematical equations and identifies power targets done algebraic computations.

The investigation squad represented nan analyzable interactions among genes wrong a compartment arsenic a "logic circuit diagram" (Boolean network). Based connected this, they visualized really a compartment responds to outer stimuli arsenic a "landscape map" (phenotype landscape).

By applying a mathematical method called nan "semi-tensor product," they developed a measurement to quickly and accurately cipher really nan wide cellular consequence would alteration if a circumstantial cistron were controlled.

However, because nan cardinal genes that find existent cellular responses number successful nan thousands, nan calculations are highly complex. To reside this, nan investigation squad applied a numerical approximation method (Taylor approximation) to simplify nan calculations. In elemental terms, they transformed a analyzable problem into a simpler look while still yielding astir identical results.

Through this, nan squad was capable to cipher which unchangeable authorities (attractor) a compartment would scope and foretell really nan cell's authorities would alteration erstwhile a peculiar cistron was controlled. As a result, they were capable to place halfway cistron power targets that could reconstruct abnormal cellular responses to states astir akin to normal.

Professor Cho's squad applied nan developed power exertion to various cistron networks and verified that it tin accurately foretell cistron power targets that reconstruct altered stimulus-response patterns of cells backmost to normal.

In particular, by applying it to bladder crab compartment networks, they identified cistron power targets tin of restoring altered responses to normal. They besides discovered cistron power targets successful large-scale distorted cistron networks during immune compartment differentiation that are tin of restoring normal stimulus-response patterns. This enabled them to lick problems that antecedently required only approximate searches done lengthy machine simulations successful a accelerated and systematic way.

This study is evaluated arsenic a halfway original exertion for nan improvement of nan Digital Cell Twin model, which analyzes and controls nan phenotype scenery of cistron networks that find compartment fate. In nan future, it is expected to beryllium wide applicable crossed nan life sciences and medicine, including caller anticancer therapies done crab reversibility, supplier development, precision medicine, and reprogramming for compartment therapy."

Professor Kwang-Hyun Cho, KAIST

KAIST master's student Insoo Jung, PhD student Corbin Hopper, PhD student Seong-Hoon Jang, and PhD student Hyunsoo Yeo participated successful this study. The results were published online connected August 22 in Science Advances, an world diary published by nan American Association for nan Advancement of Science (AAAS).
※ Paper title: "Reverse Control of Biological Networks to Restore Phenotype Landscapes"
※ DOI: https://www.science.org/doi/10.1126/sciadv.adw3995

This investigation was supported by nan Mid-Career Researcher Program and nan Basic Research Laboratory Program of nan National Research Foundation of Korea, funded by nan Ministry of Science and ICT.