mutscan - a flexible R package for efficient end-to-end analysis of multiplexed assays of variant effect data

Abstract

Multiplexed assays of variant effect (MAVE) experimentally measure the fitness of large numbers of sequence variants by selective enrichment of sequences with desirable properties followed by quantification by sequencing. mutscan is an R package for flexible analysis of such experiments, covering the entire workflow from raw reads up to statistical analysis and visualization. Core components are implemented in C++ for efficiency. Various experimental designs are supported, including single or paired reads with optional unique molecular identifiers. To find variants with changed relative abundance, mutscan employs established statistical models provided in the edgeR and limma packages. mutscan is available from https://github.com/fmicompbio/mutscan.

MoCHI: neural networks to fit interpretable models and quantify energies, energetic couplings, epistasis and allostery from deep mutational scanning data

“…The only configuration information strictly required to run MoCHI is a plain text model design file that defines the neural network architecture, and which additionally includes a path to the pre-processed DMS data for each observed phenotype (table rows) as provided by tools such as Enrich2 33 , DiMSum 34 , mutscan 35 or Rosace 36 (see Methods). MoCHI conveniently handles all low-level data manipulation tasks required for model fitting including the definition of training-test-validation data splits and 1-hot encoding of sequence features from AA sequences.…”

“…MoCHI performs model inference accounting for empirical noise (σ n ) in observed phenotype estimates ( y n ) as supplied by the user and provided by tools such as Enrich2 33 , DiMSum 34 , mutscan 35 or Rosace 36 . MoCHI can be configured to train the parameters of genotype-phenotype models assuming a Gaussian noise model: where is the predicted phenotype score of variant n .…”

Optimization of a deep mutational scanning workflow to improve quantification of mutation effects on protein-protein interactions

“…Raw read counts were processed and transformed into count tables using the mutscan R package [25]. Samples with an average Phred score below 20 and incorrect amplicon structure were discarded at this step.…”

Dynamics and plasticity of stem cells in the regenerating human colonic epithelium

“…Mature organoids were trypsinized and seeded as described for the maintenance cultures into 6-well culture plates. At 24,48,72,96,120,144,168,192 and 240 h after seeding, organoids were collected using ice-cold DMEM+++ and singularized as described above. Dissociated cells were filtered through a 40 µm filter (Falcon) and sorted/counted on a BD FACSAria III with a 100 µm nozzle into a 1.5 ml tube.…”