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ivan-aksamentov committed Dec 4, 2024
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## Unreleased

Updated private mutation QC metrics such that the typical value is the median value and the cutoff is the 97.5th percentile of private mutation counts assigned to unique GISAID sequences.

## 2024-11-19T14:18:53Z

Updated tree.json to add mutation calling relative to A/American_wigeon/North_Carolina/AH0182517/2022

## 2024-05-08T11:39:52Z

Initial release for Nextclade v3!

Read more about Nextclade datasets in the documentation: https://docs.nextstrain.org/projects/nextclade/en/stable/user/datasets.html
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# H5Nx clade `2.3.4.4` dataset with A/Astrakhan/3212/2020 reference

| attribute | value |
| -------------------- | ---------------------------------------- |
| authors |[Jordan Ort](https://lmoncla.github.io/monclalab/team/JordanOrt/), [Louise Moncla](https://lmoncla.github.io/monclalab/team/LouiseMoncla/)|
| dataset name | H5Nx clade `2.3.4.4` (provisional) |
| reference strain | A/Astrakhan/3212/2020(H5N8) |
| reference accession | EPI1846961 |


## Authors and contacts

Maintained by: [Jordan Ort](https://lmoncla.github.io/monclalab/team/JordanOrt/)

With the help from: [Louise Moncla](https://lmoncla.github.io/monclalab/team/LouiseMoncla/), Todd Davis, Tommy Lam, Samuel Shephard, Richard Neher

## Scope of this dataset
This dataset uses a current H5 candidate vaccine virus (CVV) from clade `2.3.4.4` (A/Astrakhan/3212/2020) as a reference and is suitable for the analysis of H5 sequences belonging to clade `2.3.4.4` and its sub-clades `2.3.4.4a` through `2.3.4.4h`. Sequences belonging to other clades cannot be annotated by this dataset and will be left `unassigned`.

## Features
This dataset supports

* Assignment to clades and subclades based on the provisional nomenclature defined by the WHO/FAO/WOAH H5 Nomenclature Working Group
* Sequence quality control (QC)
* Phylogenetic placement
* Annotations for glycosylation sties, HA cleavage site sequence, and presence/absence of a polybasic cleavage site


## Clades of H5Nx avian influenza viruses

The WHO/FAO/WOAH H5 Nomenclature Working Group define "clades" using HA gene seguences, and define clades as genetically distinct, monophyletic groups of viruses. Viruses falling into a given clade share a common ancestor with significant bootstrap support and have low levels of within-clade diversity. [Past nomenclature updates](https://onlinelibrary.wiley.com/doi/10.1111/irv.12324) have required viruses in the same clade to be monophyletic with bootstrap suppor of at least 60%, with within-clade pairwise distances of less than 1.5%. These requirements are sometimes relaxed, and clades are periodically updated to account for expanding viral diversity.

Since 2006, clade `2.3.4.4` viruses have circulated continuously and diversified extensively into multiple sub-clades. To account for this expansion, clade `2.3.4.4` is being split into eight additional sub-clades, named `2.3.4.4a` through `2.3.4.4h` due to high circulating diversity within the clade.

This Nextclade dataset incorporates these provisional `2.3.4.4` sub-clades.

## Alternative, and complementary approaches for H5 clade assignment
Two additional tools exist for assigning clades to H5 viruses that accommodate the recent `2.3.4.4` clade splits.

1. [LABEL](https://wonder.cdc.gov/amd/flu/label/): this command-line tool is built and maintained by Sam Shepard, and performs clade assignment for all current `2.3.4.4` and `2.3.2.1` clade splits.
2. [BVBRC Subspecies Classification Tool](https://www.bv-brc.org/app/SubspeciesClassification): this is a drag and drop tool that classifies a variety of viruses, including influenza A H1N1, H3N2, and H5N1.

The clade assignments in this Nextclade dataset were validated against LABEL assignments and shown to be generally well-matched across subclades. The figure below shows a direct comparison of assignments for 1883 HA sequences from GISAID, performed using LABEL and this NextClade dataset for clade `2.3.4.4` and its subclades.

![Figure 1: Comparison between LABEL and Nextclade for 2.3.2.1 assignments](https://raw.githubusercontent.com/moncla-lab/h5nx-Clades/main/jordan-h5-clades/testing-nextclade-datasets/2344/files/20240430_2344.png)

## What is Nextclade dataset

Read more about Nextclade datasets in Nextclade documentation: https://docs.nextstrain.org/projects/nextclade/en/stable/user/datasets.html
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