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Biology subjects

Gollub, M. G.

Publications and source records attributed to Gollub, M. G..

3 recordsLinked to original sources

Manufacturing-Aware Generative Model Architectures Enable Biological Sequence Design and Synthesis at Petascale

We introduce a method to reduce the cost of synthesizing proteins and other biological sequences designed by a generative model by as much as a trillion-fold. In particular, we make our generative models manufacturing-aware, such that model-designed sequences can be efficiently synthesized in the real world with extreme parallelism. We demonstrate by training and synthesizing samples from generative models of antibodies, T cell antigens and DNA polymerases. For example, we train a manufacturing-aware generative model on 300 million observed human antibodies and synthesize[~] 1017 generated designs from the model, achieving a sample quality comparable to a state-of-the-art protein language model, at a cost of 103 dollars. Using previous methods, synthesis of a library of the same accuracy and size would cost roughly a quadrillion (1015) dollars.

bioengineering↗

ENKIE: A package for predicting enzyme kinetic parameter values and their uncertainties

Relating metabolite and enzyme abundances to metabolic fluxes requires reaction kinetics, core elements of dynamic and enzyme cost models. However, kinetic parameters have been measured only for a fraction of all known enzymes, and the reliability of the available values is unknown. The ENzyme KInetics Estimator (ENKIE) uses Bayesian Multilevel Models to predict value and uncertainty of KM and kcat parameters. Our models use five categorical predictors and achieve prediction performances comparable to deep learning approaches that use sequence and structure information. They provide accurate uncertainty predictions and interpretable insights into the main sources of uncertainty. We expect our tool to simplify the construction of priors for Bayesian kinetic models of metabolism.

systems biology↗

Probabilistic Thermodynamic Analysis of Metabolic Networks

Random sampling of metabolic fluxes can provide an unbiased description of the capabilities of a metabolic network. However, current sampling approaches do not model thermodynamics explicitly, leading to inaccurate predictions of an organisms potential or actual metabolic operations. We present a probabilistic framework combining thermodynamic quantities with steady-state flux constraints to analyze the properties of a metabolic network. It includes methods for probabilistic metabolic optimization and for joint sampling of thermodynamic and flux spaces. Applied to a model of E. coli, we use the methods to reveal known and novel mechanisms of substrate channeling, and to accurately predict reaction directions and metabolite concentrations. Interestingly, predicted flux distributions are multimodal, leading to discrete hypotheses on E. coli s metabolic capabilities. C++ source code with MATLAB interface available at https://gitlab.com/csb.ethz/pta.

systems biology↗