India’s first XE variant case misclassified? Bengaluru labs disagree

The Bengaluru-based companies that are part of the Indian SARS-CoV-2 Genomics Consortium (INSACOG) are surprised that the central government has branded the first XE variant case as a misclassification due to an analysis error by the software.

When Mumbai reported what it said was India’s first case of the XE variant of the Covid-causing virus, the Centre responded thus: “The automated software for variant annotation presently misclassifies any Omicron with specific Delta variants as XE. This could be a sequencing or analysis error. The only way to verify is manually checking from raw data.”

A scientist from the Bengaluru-based MedGenome Labs said, “A standard laboratory with capabilities should be able to identify it. Since enough cases of this variant have come up in the UK and we know its annotations, I don’t think premier national labs will make sequencing or analysis errors. The variant’s genome data is constantly getting updated by institutes globally.”

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He continued, “If there are new variations which are not updated in international databases at all, then it becomes tricky to identify. But XE’s data is now publicly available. So unless a particular lab has not updated its pipeline, only then can they miss it.” He spoke on the condition of anonymity.

At least four private labs in Bengaluru are part of the INSACOG network.

Dr Geetha Nagaraj, co-principal investigator, Central Research Laboratory, Kempegowda Institute of Medical Sciences, said: “Now, there are 473 sequences in GISAID with the XE variant. But people think it is a sequencing artifact (error) in India that has led to it (the first case identified here). There is also an XF variant. It is more divergent than Ba.1 and Ba.2. C14599T is the unique mutation of this lineage. It has both mutations from Ba.1 and Ba.2.”

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Dr Raja Mugasimangalam, CEO and founder of Genotypic Technology, said he didn’t think it was a software glitch.

“The mutations in a sample should be mapped to all known variants and then one should choose. Low sequence coverage and not updating the database can result in misclassification. Two labs of the National Institute of Virology are using our Commander software which updates every day. Commander is the software we made for Covid analysis and is widely used in India.”

Nextclade is a tool that identifies differences between sequences and a reference sequence used by Nextstrain and then uses these differences to assign sequences to clades. The pangolin web app is maintained by the Centre for Genomic Pathogen Surveillance. It helps assign SARS-CoV-2 genome sequences to global lineages.

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A senior scientist from Strand Life Sciences said: “We use Pangolin or Nextclade to identify variants and mutations. Others may be using the Dragen pipeline from Illumina. There are several pipelines, free and paid. Each company might have a preferred pipeline for their analysis.”

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