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A machine learning toolkit for genetic engineering attribution to facilitate biosecurity.

ABSTRACT: The promise of biotechnology is tempered by its potential for accidental or deliberate misuse. Reliably identifying telltale signatures characteristic to different genetic designers, termed 'genetic engineering attribution', would deter misuse, yet is still considered unsolved. Here, we show that recurrent neural networks trained on DNA motifs and basic phenotype data can reach 70% attribution accuracy in distinguishing between over 1,300 labs. To make these models usable in practice, we introduce a framework for weighing predictions against other investigative evidence using calibration, and bring our model to within 1.6% of perfect calibration. Additionally, we demonstrate that simple models can accurately predict both the nation-state-of-origin and ancestor labs, forming the foundation of an integrated attribution toolkit which should promote responsible innovation and international security alike.

SUBMITTER: Alley EC

PROVIDER: S-EPMC7722865 | biostudies-literature | 2020 Dec

REPOSITORIES: biostudies-literature

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A machine learning toolkit for genetic engineering attribution to facilitate biosecurity.

Alley Ethan C EC Turpin Miles M Liu Andrew Bo AB Kulp-McDowall Taylor T Swett Jacob J Edison Rey R Von Stetina Stephen E SE Church George M GM Esvelt Kevin M KM

Nature communications 20201208 1

The promise of biotechnology is tempered by its potential for accidental or deliberate misuse. Reliably identifying telltale signatures characteristic to different genetic designers, termed 'genetic engineering attribution', would deter misuse, yet is still considered unsolved. Here, we show that recurrent neural networks trained on DNA motifs and basic phenotype data can reach 70% attribution accuracy in distinguishing between over 1,300 labs. To make these models usable in practice, we introdu ...[more]

PMID: 33293535

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Project description:BACKGROUND: Altering a protein's function by changing its sequence allows natural proteins to be converted into useful molecular tools. Current protein engineering methods are limited by a lack of high throughput physical or computational tests that can accurately predict protein activity under conditions relevant to its final application. Here we describe a new synthetic biology approach to protein engineering that avoids these limitations by combining high throughput gene synthesis with machine learning-based design algorithms. RESULTS: We selected 24 amino acid substitutions to make in proteinase K from alignments of homologous sequences. We then designed and synthesized 59 specific proteinase K variants containing different combinations of the selected substitutions. The 59 variants were tested for their ability to hydrolyze a tetrapeptide substrate after the enzyme was first heated to 68 degrees C for 5 minutes. Sequence and activity data was analyzed using machine learning algorithms. This analysis was used to design a new set of variants predicted to have increased activity over the training set, that were then synthesized and tested. By performing two cycles of machine learning analysis and variant design we obtained 20-fold improved proteinase K variants while only testing a total of 95 variant enzymes. CONCLUSION: The number of protein variants that must be tested to obtain significant functional improvements determines the type of tests that can be performed. Protein engineers wishing to modify the property of a protein to shrink tumours or catalyze chemical reactions under industrial conditions have until now been forced to accept high throughput surrogate screens to measure protein properties that they hope will correlate with the functionalities that they intend to modify. By reducing the number of variants that must be tested to fewer than 100, machine learning algorithms make it possible to use more complex and expensive tests so that only protein properties that are directly relevant to the desired application need to be measured. Protein design algorithms that only require the testing of a small number of variants represent a significant step towards a generic, resource-optimized protein engineering process.

Dataset Information

A machine learning toolkit for genetic engineering attribution to facilitate biosecurity.

Publications

A machine learning toolkit for genetic engineering attribution to facilitate biosecurity.

Similar Datasets

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