Uncovering structural plasticity of Enterovirus A through deep insertional and deletional scanning

Insertions and deletions (InDels) are essential sources of novelty in protein evolution. In RNA viruses, InDels cause dramatic phenotypic changes that contribute to the emergence of viruses with altered immune profiles and host engagement. This work aims to comprehensively quantify the mutational tolerance of an RNA virus to insertion, deletion, and substitution. Using Enterovirus A71 (EV-A71) as a prototype for the Enterovirus A species (EV-A) of picornaviruses, we engineered approximately 45,000 insertions, 6,000 deletions, and 41,000 amino acid changes across the 2,193 coding positions of the EV-A71 proteome, quantifying their effects on viral fitness and comprehensively mapping evolutionary constraint across the viral proteome. In contrast with amino acid changes, the vast majority of InDels are lethal to virus growth. Most that are tolerated reside at a few hotspot regions. These tolerant sites highlight structurally flexible and mutationally plastic regions of EV-A71 proteins that..., These data were collected by sequencing the input and output libraries from deep mutational, insertional, and deletional scanning experiments. Data was processed by next-gen sequencing pipelines, in-house scripts, and published software to interpret the fitness effects of mutations engineered in the EV-A71 genome. Data was visualized using R packages, including ggplot2. , , # Uncovering structural plasticity of Enterovirus A through deep insertional and deletional scanning

[https://doi.org/10.5061/dryad.866t1g1xm](https://doi.org/10.5061/dryad.866t1g1xm)

## Description of the data and file structure

The files are organized in the following fashion: 

File directory tree:

```
.
├── 1_Molecular_Biology_Supp_Information
│   ├── SupplementalFile1_BB_Free_Assembly.fasta
│   ├── SupplementalFile2_Insertion_Capsid.fasta
│   ├── SupplementalFile3_Insertion_Replication.fasta
│   ├── SupplementalFile4_Deletion_Capsid.fasta
│   ├── SupplementalFile5_Deletion_Replication.fasta
│   ├── SupplementalFile6_DMS_Capsid.fasta
│   ├── SupplementalFile7_DMS_Replication.fasta
│   ├── SupplementalFile8_Chloramphenicol_Casette.fasta
│   └── SupplementalFile9_5AA_Oligopool.fasta
├── 2_Enrich2_Dataframes
│   ├── 5_AA_Insertion
│   │   ├── Capsid
│   │   │   ├── main_identifiers_scores_shared_full.tsv
│   │   │   └── main_identifiers_scores.tsv
│   │   └── Replication
│   │   ...