Assaf A. Gilad

Adrian Ratwatte, Samitha Somathilaka, Sasitharan Balasubramaniam et al.

The Gene Regulatory Network (GRN) of biological cells governs a number of key functionalities that enables them to adapt and survive through different environmental conditions. Close observation of the GRN shows that the structure and operational principles resembles an Artificial Neural Network (ANN), which can pave the way for the development of Biological Artificial Intelligence. In particular, a gene's transcription and translation process resembles a sigmoidal-like property based on transcription factor inputs. In this paper, we develop a mathematical model of gene-perceptron using a dual-layered transcription-translation chemical reaction model, enabling us to transform a GRN into a Gene Regulatory Neural Network (GRNN). We perform stability analysis for each gene-perceptron within the fully-connected GRNN sub network to determine temporal as well as stable concentration outputs that will result in reliable computing performance. We focus on a non-linear classifier application for the GRNN, where we analyzed generic multi-layer GRNNs as well as E.Coli GRNN that is derived from trans-omic experimental data. Our analysis found that varying the parameters of the chemical reactions can allow us shift the boundaries of the classification region, laying the platform for programmable GRNNs that suit diverse application requirements.

Iliya Miralavy, Alexander Bricco, Assaf Gilad et al.

Protein engineers conventionally use tools such as Directed Evolution to find new proteins with better functionalities and traits. More recently, computational techniques and especially machine learning approaches have been recruited to assist Directed Evolution, showing promising results. In this paper, we propose POET, a computational Genetic Programming tool based on evolutionary computation methods to enhance screening and mutagenesis in Directed Evolution and help protein engineers to find proteins that have better functionality. As a proof-of-concept we use peptides that generate MRI contrast detected by the Chemical Exchange Saturation Transfer contrast mechanism. The evolutionary methods used in POET are described, and the performance of POET in different epochs of our experiments with Chemical Exchange Saturation Transfer contrast are studied. Our results indicate that a computational modelling tool like POET can help to find peptides with 400% better functionality than used before.