Create the delivery report

[LilyAnderssonLee]

Reports for molecular biologist

Mutation table: List all the mutations

Sample_name	Gene_name	Mutations	Mutations_type	Mutations_comments	isInsertion	isDeletion	isApobecMutation	isApobecDRM	isUnusual	isSDRM	hasStop	Mutation_AF	Coverage	indel (>5%)	Notes

Notes:

• Mutations: Stored at the field text under the primaryType
• Mutations_type: PR gene: res/accessory/other; RT gene: NRTI/NNRTI/other; IN gene: This value stored at the field primaryType, see the example:

          {
            "consensus": "D",
            "position": 232,
            "AAs": "N",
            "isInsertion": false,
            "isDeletion": false,
            "isApobecMutation": false,
            "isApobecDRM": true,
            "isUnusual": false,
            "isSDRM": false,
            "hasStop": false,
            "primaryType": "Accessory",
            "text": "D232N"
          }

• Mutations_comments: Stored in the field text

{
                "mutations": [
                  {
                    "text": "L210W",
                    "primaryType": "NRTI",
                    "comments": [
                      {
                        "type": "NRTI",
                        "text": "L210W is a TAM that usually occurs in combination with M41L and T215Y. The combination of M41, L210W and T215Y causes high-level resistance to AZT and intermediate resistance to ABC and TDF."
                      }
                    ]
                  }
                ],
                "score": 5.0
              }

• Mutation_AF: stored vcf or output from ivar variants
• Mutation_coverage: if viralrecon doesn't generate one, then add a method to calculate it.

WWLAB

Mutation table: report mutations containing the Mutations_comment

Sample_name	Gene_name	Mutations	Mutations_type	Mutations_comments

drug_report

Sample_name	Drug_class	Drugs	Total_score	Res_status

          {
            "drugClass": {
              "name": "NNRTI"
            },
            "drug": {
              "name": "DPV",
              "displayAbbr": "DPV"
            },
            "score": 0,
            "level": 1,
            "partialScores": [],
            "text": "Susceptible"
          }

• Res_status:High-Level Resistance; intermediate; low-level resistance; susceptible; Potential Low-Level Resistance.

[LilyAnderssonLee]

See the example output from Sierra-local :
https://github.com/genomic-medicine-sweden/hiv-typing-proj/blob/main/24BG107164_HIVDB9.8.json

[LilyAnderssonLee]

Refer to how codfreq generate the codfreq table to extract the allele frequency and coverage.

[LilyAnderssonLee]

@svarona I am not sure if we need to include insertions or deletions when extracting mutation_coverage and mutation_AF from codfreq, since we ignored that in our previous research study. I need to set up a meeting with our clinicians to discuss about that.

[LilyAnderssonLee]

Besides generation of above csv files, create a html report combining all those csv tables in the html report. Then put the warning message at the top the html report.

Create separate csv files for each sample.

[LilyAnderssonLee]

WWLab system can define which columns should be uploaded. So it's fine with unused columns in csv file.
Add a column Notes to indicates the warning message of missing regions.

[LilyAnderssonLee]

Mutation AF: test and comparing with two different settings.

• Consider insertions/deletions
• ignore insertions/deletions

[LilyAnderssonLee]

Add a extra column indel > 5% as a warning to indicate if it caused by artefacts, dead viruses or low viral load.

[LilyAnderssonLee]

• Create separate csv files for each samples.

• Add a button in the html report to switch between samples.

• Generate genetic distance table for a batch, and add an extra column pass if 70% or 50% bases of pol gene are sequenced

[svarona]

Differences in resistance/mutations between HIVdb and sierra-local

• Sierra-local is testing or giving results for ALL the drugs listed in the XML file while HIVdb is not
• regarding comment section:
  • sierra-local is only giving comments under the "drugScores" section, so only comments for mutations that are related to a drug would be included in the reports
  • HIVdb includes all the comments in the XML file for all mutation types.
• Regarding the mutations shown:
  • sierra-local processes the consensus, which as we stablished in the settings includes upt to 80% of AF mutations on it
  • HIVdb taking the reads has mutations with 82% (+16%) AF mutations, that's why we are missing some of them in sierra-local (thresholds tunning matter)

[LilyAnderssonLee]

Sierra-local doesn't report comments for other type of mutations.If needed,

• update the algorithms in sierra-local to report all comments like what HIVdb reports.
• or pull all comments of others from the HIVdb and report this list

[LilyAnderssonLee]

To do list (not so soon)

• enable to run viralrecon with the consensus as a input instead of FASTQ files
• discussion with Emma Hodcroft about subtype generated by nextclade. How does nextclade handle the unusual combinations?
• Can you chose the fragments in nextclade instead of the whole genome?
• Check the drug resistance status for missing codons - update the sierra-local algorithm
• Update sierra-local to detect the mutations and drugs in gag gene.

Nucleotide diversity

• Add nucleotide diversity estimation feature to nf-core/viralrecon
• Re-compute the theta for historic data and compare if we get the same results
• Analyze Biomarkers generated after 2022.
• The final goal is to estimate the pct of andiagnostic patients

[svarona]

The python to create the comment table, the comments .json file and the comments CSV files are included in this PR:
nf-core/viralrecon#559

You can acces the table in this link in the PR until it is merged in viralrecon/assents

[svarona]

Delivery report created in this PR:
nf-core/viralrecon#559