Enrich: software for analysis of protein function by enrichment and depletion of variants

By Douglas M. Fowler, Carlos L. Araya, Wayne Gerard, Stanley Fields. 2011

130 citations recorded by the source corpus.

Summary: Measuring the consequences of mutation in proteins is critical to understanding their function. These measurements are essential in such applications as protein engineering, drug development, protein design and genome sequence analysis. Recently, high-throughput sequencing has been coupled to assays of protein activity, enabling the analysis of large numbers of mutations in parallel. We present Enrich, a tool for analyzing such deep mutational scanning data. Enrich identifies all unique variants (mutants) of a protein in high-throughput sequencing datasets and can correct for sequencing errors using overlapping paired-end reads. Enrich uses the frequency of each variant before and after selection to calculate an enrichment ratio, which is used to estimate fitness. Enrich provides an interactive interface to guide users. It generates user-accessible output for downstream analyses as well as several visualizations of the effects of mutation on function, thereby allowing the user to rapidly quantify and comprehend sequence–function relationships. Availability and Implementation: Enrich is implemented in Python and is available under a FreeBSD license at http://depts.washington.edu/sfields/software/enrich/. Enrich includes detailed documentation as well as a small example dataset. Contact: dfowler@uw.edu; fields@uw.edu Supplementary Information: Supplementary data is available at Bioinformatics online.

Subfields: Genetics, Molecular Biology

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Citations in the corpus

Deep mutational scanning of an RRM domain of the Saccharomyces cerevisiae poly(A)-binding protein (2013, methodology): “Scoring the performance of library variants We used the Enrich software package (Fowler et al. 2011) to remove low-quality reads (discarding reads with base Q score <20); to determine the location and identity of mutations, while filtering out variants with insertions or deletions; to calculate the…”
Massively Parallel Functional Analysis of BRCA1 RING Domain Variants (2015, methodology): “The matched barcodes were converted to the sequence of the full length BRCA1(2–304) assembly and the Enrich software package (Fowler et al. 2011) was used to determine locations and identity of substitutions and to tally the number of times each variant appeared in each population (Table S2).”
Sampling and energy evaluation challenges in ligand binding protein design (2017, unknown): “Paired-end sequences were aligned by PEAR(30) and analyzed with scripts adapted from Enrich.(31)”
Measuring the activity of protein variants on a large scale using deep mutational scanning (2014, methodology): “Enrich, a software package written for this purpose, transforms raw sequencing data into variant functional scores 32 ( Fig.”
Computational design of environmental sensors for the potent opioid fentanyl (2017, methodology): “This resulted in 3,992,873 full length DNA reads (Supplementary file 5) that were translated to their corresponding protein sequence and mutation frequencies were determined using the Enrich software package (Fowler et al., 2011).”
A fundamental protein property, thermodynamic stability, revealed solely from large-scale measurements of protein function (2012, methodology): “The data were analyzed using the Enrich software package (36).”
High-throughput Analysis of in vivo Protein Stability* (2013, methodology): “Analysis of Sequence Data—The identity of each mutation and its frequency in the input and selected libraries were determined by the Enrich software package (14).”
Computational design of a protein-based enzyme inhibitor. (2013, unknown): “Enrichment ratios are plotted in Fig.”
Activity-enhancing mutations in an E3 ubiquitin ligase identified by high-throughput mutagenesis (2013, methodology): “The Enrich software package (26) was used to determine the locations and identity of mutations in the assemblies, as well as the frequency at which”