Page 37 - Annual report 2021-22

Annual Report 2021-22 |

Anurag Agrawal

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Anurag Agrawal’s lab works at the intersection of lung physiology and big data analytics.

Anurag has had a long-standing interest in lung health. Vital Capacity (VC), i.e. capacity for life, for the
amount of air we can exhale after a maximal inspiration (FVC for forceful exhalation). More than a
hundred years later, Hutchinson's original premise was finally vindicated in the Framingham Study,
where low FVC was one of the best predictors of cardiopulmonary disease, cardiac failure and
premature death; better than blood cholesterol. Apparently healthy Indians have the lowest FVC
amongst all major ethnic groups, about a third lower than white Americans or Europeans; putting us
in the danger category based on western studies but treated as a statistical normal for our ethnic
group. In a project aiming to decipher the physiological underpinnings of low lung-function in
apparently healthy Indians, his group undertook a study to measure parameters of lung function and
inflammation across a cross-sectional sample of 3500 subjects. From about 3500 spirometric studies
across India (9-50 years subjects, adjusted for age, gender, height, and weight and expressed as a z
score against global reference values), this study confirmed that FVC was significantly lower in Indians,
at every site except at higher altitudes, and deteriorated further with advancing age. Poor lung
function in Indians was also associated with other markers of health. Though ethnicity-based lung
function differences were observed in Indian geo-ethnic groups, these associations of vital capacity
with health parameters remained significant even after adjusting for ethnicity. These results support
the primary hypothesis of low lung function in apparently healthy Indians being in an abnormal state,
which would challenge the current method of defining population norms from a statistical cut-off. In
these adolescent children low lung function was associated with elevated levels of pro-inflammatory
cytokines (i.e., TNF-alpha, IL-8, IFN-gamma, IL-17). Using Latent profile analysis, a cluster of very thin
children with higher inflammation, comprising about 35% of the population, had the poorest lung
function. Poor growth during childhood, associated with chronic systemic inflammation, and
subsequent early decline lead to widely prevalent pathophysiological low lung function with
characteristics of small airway dysfunction.

Through his interests in lung physiology and data analytics Anurag has provided leadership in the
understanding of various aspects associated with the COVID19 pandemic. Partnering with Intel, IIT
Hyderabad and several research teams across CSIR, Anurag provided leadership in faster testing and
sequencing of SARS-CoV2. RT-PCR based testing of individuals suspected of SARS-CoV-2 infection,
asymptomatic or symptomatic, was done across length and breadth of India. This included
collaborators from CSIR-IIP, CSIR-CLRI and CSIR-IMTECH. Early use of the portable, cheaper, and faster
RT-PCR based system from MolBio (https://www.molbiodiagnostics.com/) complemented the
traditional RT-PCR systems. The data ingestion pathway was set up to transfer the data from the
gateway to the central Data exchange at IGIB. RT-PCR tests for more than 20,000 individuals. The RT-
PCR positive RNA sample from the CSIR labs as well as other clinical partners was sourced to CSIR-IGIB
for Integrative genomics of the SARS-CoV-2. The integrative genomics approach towards SARS-CoV-2
required development of orthogonal sequencing methods inclusive of amplicon-based, probe-based
enrichment and de novo shotgun sequencing. It was also incumbent to optimise the choice of
sequencing platforms based on dual objective of data output and research question. The team