publications

2023

1. Advances in generative modeling methods and datasets to design novel enzymes for renewable chemicals and fuels

   Rana A Barghout ,  Zhiqing Xu ,  Siddharth Betala , and 1 more author

   Current Opinion in Biotechnology, Dec 2023

   Abs

   Biotechnology has revolutionized the development of sustainable energy sources by harnessing biomass as a feedstock for energy production. However, challenges such as recalcitrant feedstocks and inefficient metabolic pathways hinder the large-scale integration of renewable energy systems. Enzyme engineering has emerged as a powerful tool to address these challenges by enhancing enzyme activity, specificity, and stability. Generative machine learning (ML) models have shown great promise in accelerating protein design, allowing for the generation of novel protein sequences with desired properties by navigating vast spaces. This review paper aims to summarize the state of the art in generative models for protein design and how they can be applied to bioenergy applications, including the underlying architectures and training strategies. Additionally, it highlights the importance of high-quality datasets for training and evaluating generative models, organizes available datasets for generative protein design, and discusses the potential of applying generative models to strain design for bioenergy production.

2022

1. KinMod database: a tool for investigating metabolic regulation

   Kiandokht Haddadi ,  Rana Ahmed Barghout ,  and  Radhakrishnan Mahadevan

   Database, Jan 2022

   Abs

   The ability of current kinetic models to simulate the phenotypic behaviour of cells is limited since cell metabolism is regulated at different levels including enzyme regulation. The small molecule regulation network (SMRN) enables cells to respond rapidly to environmental fluctuations by controlling the activity of enzymes in metabolic pathways. However, SMRN is not as well studied relative to metabolic networks. The main contributor to the lack of knowledge on this regulatory system is the sparsity of experimental data and the absence of a standard framework for representing available information. In this paper, we introduce the KinMod database that encompasses more than 2 million data points on the metabolism and metabolic regulation network of 9814 organisms KinMod database employs a hierarchical data structure to: (i) signify relationships between kinetic information obtained through in-vitro experiments and proteins, with an emphasis on SMRN, (ii) provide a thorough insight into available kinetic parameters and missing experimental measurements of this regulatory network and (iii) facilitate machine learning approaches for parameter estimation and accurate kinetic model construction by providing a homogeneous list of linked omics data. The hierarchical ontology of the KinMod database allows flexible exploration of data attributes and investigation of metabolic relationships within- and cross-species. Identifying missing experimental values suggests additional experiments required for kinetic parameter estimation. Linking multi-omics data and providing data on SMRN encourages the development of novel machine learning techniques for predicting missing kinetic parameters and promotes accurate kinetic model construction of cells metabolism by providing a comprehensive list of available kinetic measurements. To illustrate the value of KinMod data, we develop six analyses to visualize associations between data classes belonging to separate sections of the metabolism. Through these analyses, we demonstrate that the KinMod database provides a unique framework for biologists and engineers to retrieve, evaluate and compare the functional metabolism of species, including the regulatory network, and discover the extent of available and missing experimental values of the metabolic regulation.Database URL: https://lmse.utoronto.ca/kinmod/KINMOD.sql.gz

2020

1. Foundations of Chemical and Biological Engineering I

   Jonathan Verret ,  Rosie Qiao ,  and  Rana A. Barghout

   Aug 2020