Page 32 - Annual report 2021-22

Annual Report 2021-22 |

Sridhar Sivasubbu

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Sridhar Sivasubbu works on functional genomics to understand the genetics and biological
mechanisms of rare genetic diseases.

In collaboration with Vinod Scaria, he developed the IndiGen app as part of the GenomeApp project.
The IndiGenome Card (GenomeApp) is a unique ID and barcode on a card which can be used to access
the genomic data interpretation on a cloud service over a mobile/web application. The system enables
relevance of interpretation of genetic variants and an easy method to access specific genetic findings
on clinical request. These could be for the primary indications (indications for the diagnosis of the
disease or genetic variants) or secondary indications (secondary indications could be for modifier loci,
pharmacogenomic variants, incidental findings etc.) which can provide insights into the prognosis of
the disease. The GenomeApp was developed, and pilot tested in Indian samples.
Over 1200 samples were collected through the clinical network. These included cases of undiagnosed
familial diseases. Samples pertaining to the following disease cohorts were sequenced and analyzed -
dystonia, Wilson's Disease, sickle cell disease, Gaucher disease, mitochondrial disorders,
genodermatoses, primary immunodeficiency disorders, cardiac arrhythmia, epilepsy, treatable
intellectual disabilities, cerebrotendinous xanthomatosis, autoinflammatory diseases and other
undiagnosed genetic diseases. Following the genomic sequencing and analysis, genetic screening
assays for several genetic disorders were developed. These included NGS and capillary sequencing
based genetic screening assays. The goal was to couple the NGS genetic screening assays and the
GenomeCard for communicating the genomic evidence. The IndiGen App is available on Google play
store and has more than 1000+ downloads. The data on pharmacogenetic variants have been widely
accessed by the users of the app.
Under the INGEN-COV2 (Integrative Genomics of COVID-19), a collaborative project between IGIB and
CCMB, Sridhar Sivasubbu’s lab was continuously engaged in providing RT-PCR based COVID screening
to various Delhi hospitals as assigned from time to time. Testing of 4900 nasopharyngeal swabs in
VTM samples was performed for samples from various parts of the country, mainly Delhi and Ladakh
region. 510 genomes of SARS-CoV2 were sequenced and 319 were deposited in GISAID. Longitudinal
sampling from 79 COVID-19 positive mothers and infants born were enrolled in the study. During this
period, India also witnessed the challenging 2nd wave which was primarily over-represented by the
Delta variant. With increased ability of transmission, Delta variant also was dominating the vaccination
breakthroughs. Thus, during this period, SARS-CoV-2 genome sequencing was performed to
understand these aspects.

CSIR Megalab for COVID19 genomic surveillance was set up in major metro cities for keeping the
economic and commercial hubs open for business during this pandemic. The Megalab platform is
capable of undertaking detection of over 3000 COVID19 samples every 24 hours using genome
sequencing based detection. As proof-of-concept, the Megalab protocol was tested using 1504 patient
samples. The assay was successful in detection of SARS nCoV2 in over 1350 samples. The Megalab SoP
has over 98% sensitivity. Further the assay yielded an additional diagnostic yield of 8 to 10%. Using