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Pango Lineages

WGS - Angie Hinrichs - Feb. 3, 2022

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Overview

Pango nomenclature
How lineages are designated
How lineages are assigned
Example: Omicron lineages

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Pango nomenclature

“a rational and dynamic virus nomenclature that uses a phylogenetic framework to identify those lineages that contribute most to active spread… focusing on active virus lineages and those spreading to new locations”

Letters, dots, numbers
Initially proposed in bioRxiv April 2020; published Nat. Microb. Nov. 2020

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Pango nomenclature

ancestor

B

A

Wuhan/WHO4

8782T, 28144C

Wuhan/Hu-1

8782C, 28144T

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Pango nomenclature

ancestor

B

A

A.1

A.2

B.1

…

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Pango nomenclature

…

ancestor

B

A

A.1

A.2

A.2.1

B.1

B.1.1

B.1.617

…

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Pango nomenclature

…

ancestor

B

A

A.1

A.2

A.2.1

B.1

B.1.1.1

B.1.1

B.1.617

B.1.1.529

B.1.1.7

B.1.617.2

…

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Pango nomenclature

…

ancestor

BA.1

C.1

B

BA.2

BA.3

A

A.1

A.2

A.2.1

B.1

B.1.1.1

B.1.1

B.1.617

B.1.1.529

B.1.1.7

C.2

B.1.617.2

AY….

Q….

…

New letters!

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Where do lineages come from?

Pango nomenclature proposal authors

Before March 2021: mostly Áine O’Toole, U. Edinburgh
March 2021: team “Pangothon”
After March 2021: mostly Chris Ruis, U. Cambridge (“Deltathons”)

Community requests

https://github.com/cov-lineages/pango-designation/issues

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How are community requests evaluated?

Formal rules:

Monophyletic (i.e. a complete branch in the phylogenetic tree)
At least one defining mutation
At least 5 high-quality genome sequences
At least one internal node showing onward transmission
Epidemiological significance

New country or region
New wave / evidence of faster growth than other lineages
Observed or predicted change in transmissibility, immunogenicity, or pathogenicity
…

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How are community requests evaluated?

Is it monophyletic?

Early days: construct a phylogenetic tree with selected sequences
Since ~mid-2021: UCSC’s UShER tree and UShER web interface

Initially the Pango team’s idea was that people proposing new lineages would build their own phylogenetic trees out of the proposed sequences and a few hundred or thousand other sequences. However, when tens of thousands of sequences were available, and then hundreds of thousands, that approach would mean ignoring most available data.

Meanwhile, at UCSC, we had UShER, which rapidly places new sequences on trees with millions of sequences, and we’ve been running daily updates of our global SARS-CoV-2 tree since early 2021. We also provide a web interface that makes it easy to upload new sequences, have them placed on the global tree, and get local subtrees that can be viewed on Nextstrain. If sequences are already in our tree then it’s possible to just paste in the sequence names or IDs and get subtrees.

So in March 2021 I started pasting lists of sequences that people proposed as new lineages into our web interface and commenting on proposals with subtree views from UCSC’s big tree showing whether the sequences were monophyletic or not. It caught on – many lineage proposals now include screenshots of subtree views from our web interface.

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What defines a Pango lineage?

Not a set of mutations!

lineages.csv in the pango-designation github repository (>1M lines):

...

India/GJ-ICMR-NIV-INSACOG-GSEQ-3045/2021,B.1.617.2

India/PY-SEQ_294_S22_R1_001/2021,B.1.617.2

Malaysia/IMR_682164/2021,B.1.617.2

Japan/IC-1175/2021,B.1.617.2

USA/TX-CDC-ASC210037740/2021,B.1.617.2

England/WSFT-25C6539/2021,B.1.1.7

USA/MI-UM-10039543606/2021,AY.3

USA/KS-KHEL-1922/2021,AY.3

USA/KS-KHEL-1923/2021,AY.3

USA/MO-MSPHL-002099/2021,AY.3

USA/MO-MSPHL-002132/2021,AY.3

...

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How to assign a lineage to a genome sequence

pangolin

https://github.com/cov-lineages/pangolin

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A brief history of pangolin

v1.0 (April 29, 2020)

phylogenetic model (iqtree… not fast enough)

v2.0 (July 22, 2020)

pangoLEARN model (fast! sensitive to noise)

v3.0 (May 27, 2021)

pangoLEARN + scorpio/constellations + --usher option

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pangolin method: pangoLEARN vs. UShER

Decision tree model

1

0

Align to reference, mask

Binary vectors

Assigned lineage

lineageTree.pb

Align to reference, mask

Assigned lineage

User SARS-CoV-2 sequences

pangoLEARN

UShER

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Use UShER!

https://virological.org/t/sars-cov-2-lineage-assignment-is-more-stable-with-usher/781

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Use UShER!

Some incongruous changes with UShER

Many incongruous changes with pangoLEARN

When new lineages are added…

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Coming soon: pangolin v4.0

UShER default, pangoLEARN optional
scorpio/constellations can still override UShER or pangoLEARN
Optional cached assignments for speed

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Omicron lineages

Nov. 23rd 2021: First complete genomes from Botswana released on GISAID

Tom Peacock (ICL) noticed, filed an issue in pango-designation:

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Omicron lineages: first B.1.1.529

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Omicron lineages: split → BA.1, BA.2

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Omicron lineages: split → BA.1, BA.2

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Omicron lineages: and then there was BA.3

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Omicron lineages: BA.1.1

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Omicron in pangolin: mostly scorpio/const.

Omicron

AY.4

pangolin v3.0

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Pango links

cov-lineages.org
Pango.network

pango-designation github repository