Evolutionary Failure Mode Calculator

Computing & Wireless : Computing Methods

Available for licensing

Inventors

  • Jeffrey Barrick, Ph.D. , Molecular Biosciences
  • Benjamin Jack, B.S. , Institute for Cellular and Molecular Biology
  • Sean Leonard, B.S. , Institute for Cellular and Molecular Biology

Background/unmet need

Synthetic biology (including metabolic engineering and genome engineering) requires designing DNA sequences that are deployed in living organisms. These DNA sequences are subject to mutations that can cause them to rapidly malfunction. Certain DNA sequences are more stable than others. The Evolutionary Failure Mode (EFM) calculator predicts the overall genetic stability of an engineered DNA sequence and identifies hyper-mutable sites that contribute most to instability. Thus, it can be used as negative design tool for eliminating hyper-mutable sequences to make synthetic biology designs operate more predictably and reliably. 

Invention Description

The Evolutionary Failure Mode (EFM) Calculator takes a DNA sequence as input and predicts hyper-mutable sites that would lead to it being genetically unstable when constructed. The EFM Calculator predicts multiple types of unstable sites, including two major sources of potential genetic instability: deletions mediated by homologous recombination and indels caused by replication slippage on simple sequence repeats. Furthermore, it has different mutation rate models for different host organisms that are trained from a meta-analysis of the literature.

Benefits/Advantages

  • Uses distinct rate models for mutations on varying host organisms
  • Able to predict multiple types of unstable sequences

Features

  • Predicts stability of engineered DNA sequence
  • Increases reliability of synthetic biology designs

Market potential/applications

DNA sequence design, metabolic engineering, genetic engineering, computer-aided design (CAD)

Development Stage

Beta product/commercial prototype