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Deep2Full: Computational Model for Predicting Large Complementary Fraction of Deep Mutational Scan Outcomes

21 Pages Posted: 26 Oct 2018 Sneak Peek Status: Under Review

See all articles by C. K. Sruthi

C. K. Sruthi

Jawaharlal Nehru Centre for Advanced Scientific Research - Theoretical Sciences Unit

Meher Prakash

Jawaharlal Nehru Centre for Advanced Scientific Research - Theoretical Sciences Unit

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Abstract

Performing deep mutational scan with site-directed mutations of all the amino acid residues in a protein may not be practical, and may not even be required, especially if predictive computational models can be developed. Computational models are however naive to cellular response in the myriads of assay-conditions. We develop a realistic paradigm of assay context-aware predictive hybrid models. Combining minimal deep mutational studies with structure, sequence information and computational models, we predict the phenotypic outcomes quantitatively. It was demonstrated with predictions on the fitness outcomes for a few proteins. Phenotypic fitness data from as few as 15% of the mutations was sufficient for reliable prediction. Interestingly, the predictive capabilities are better with a random set of mutations rather than with a systematic substitution of all amino acids to alanine, asparagine and histidine (ANH). The model can potentially be extended for predicting the phenotypic outcomes at other concentrations of the stressor, such as in dose studies.

Keywords: Deep mutational scan, Mutational landscape, Fitness, Co-evolution, Neural networks, Computational models

Suggested Citation

Sruthi, C. K. and Prakash, Meher, Deep2Full: Computational Model for Predicting Large Complementary Fraction of Deep Mutational Scan Outcomes (October 26, 2018). Available at SSRN: https://ssrn.com/abstract=3273391 or http://dx.doi.org/10.2139/ssrn.3273391
This is a paper under consideration at Cell Press and has not been peer-reviewed.

C. K. Sruthi

Jawaharlal Nehru Centre for Advanced Scientific Research - Theoretical Sciences Unit

Bangalore-560064
India

Meher Prakash (Contact Author)

Jawaharlal Nehru Centre for Advanced Scientific Research - Theoretical Sciences Unit ( email )

Bangalore-560064
India

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