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राष्ट्रीय पशु जैव प्रौद्योगिकी संस्थान
National Institute of Animal Biotechnology
An Autonomous Institute of the Department of Biotechnology,
Ministry of Science and Technology, Government of India
राष्ट्रीय पशु जैव प्रौद्योगिकी संस्थान
National Institute of Animal Biotechnology
An Autonomous Institute of the Department of Biotechnology,
Ministry of Science and Technology, Government of India
Education:
Sarwar Azam completed M Tech degree in Computational and Systems Biology from Jawaharlal Nehru University in 2009. After working for a short period at National Institute of Plant Genome Research (NIPGR), he joined International Crop Research Center for the Semi-Arid Tropic (ICRISAT) in 2010 as Visiting Scientist (Bioinformatics). Later he continued as a Special Project Scientist at ICRISAT in the field of computational genomics. He joined NIAB in November 2013.
Selected awards, honors and fellowships:
1. Certificate of Appreciation for the outstanding contribution in the area of Functional Genomics and Bioinformatics as part of Bioclues Innovation, Research and Development (BIRD) award, 2011
2. Exceptional Scientific Article in a High Impact Journal Award, ICRISAT, 2011
3. CSIR – UGC NET examination in Life sciences held in June 2008, December 2008 & June 2009
4. DBT fellowship 2007-2009 for M.Tech. course
5. BCIL Fellowship for BITP from DBT, Govt. of India, 2006
Sarwar’s research experience spans genetics, genomics and computational biology. His major contribution has been in the field of genome sequencing where he generated reference sequences for animal and plant genomes i.e., Bos Indicus (Cattle), Cicer arietinum (chickpea) and Cajanus cajan (pigeonpea) and bacterial genomes i.e., Sphingopyxis wildii and Sphingobium fuliginis. He has also contributed in finding quantitative trait loci (QTLs) for different traits in chickpea and identified candidate genes for various traits by analysing RNAseq data in different species. He also developed pipeline to analyse NGS data for SNPs identification (ISMU), synteny visualisation (GCT) and few other databases. Currently, his research interest includes genome sequencing, transcriptomics and genome-wide association studies (GWAS) to improve the genetic and productive efficiency of livestock. He is also keen to develop fundamental knowledge and bioinformatics tools to facilitate genomic studies in animals.
The lab’s recent focus has been on the following scientific work:
1. Genomics for conservation of indigenous cattle breeds and for enhancing milk yield, Phase-I
This project was sanctioned with the aim to use cutting-edge technologies, such as Next Generation Sequencing (NGS) and array-based genotyping, to decipher the genetic makeup of indigenous cattle. The proposed plan was to sequence 20 individuals (preferably males) from each of the five well-known indigenous breeds (Gir, Sahiwal, Red Sindhi, Tharparkar, Kankrej) for their milk production, and two individuals from each of the remaining 38 breeds. This sequencing data would be analyzed to extract Single Nucleotide Polymorphisms (SNPs) in different breeds. SNPs would be prioritized from this NGS data to develop a High Density (HD) SNP chip, which would be used to genotype 50 individuals from each of the 43 indigenous breeds found in India at that time. The genotyped data would then be used to estimate various genetic parameters, such as LD flow across breeds, population genetic structure and admixture, runs of homozygosity, intra-breed distance, inter-breed distance, and inbreeding. Variants that are private to each breed, shared by two or more breeds, and allele frequencies within and across breeds would also be quantified. The project would reveal the genetic architecture and genetic relationship across all 43 indigenous breeds in terms of SNPs.
Development of a High Density SNP chip: IndiGau
Figure: Summary of analyses for the development of IndiGau SNPchip
IndiGau
2. Development of a haplotype resolved reference genome assemblies for indigenous cattle (Bos indicus)
Indigenous cattle are known for their resilience to various diseases and abiotic stress, such as drought and heat, have unique traits when compared to their western/exotic counterparts. The aim of this work is to generate a high quality reference genome for indigenous cattle. The reference genome will provide valuable information that can be used to accurately identify genes and variations that are responsible for the unique characteristics of indigenous Cattle. Using the trio-binning approach, in collaboration with USDA-ARS, we assembled two genomes, Sahiwal and Tharparkar, by sequencing the parents (Sahiwal sire and Tharparkar dam) and their daughter using long and short-read sequencing. These genome assemblies will serve as the definitive REFERENCE GENOMES for all future research related to Indigenous cattle. Both genomes have been submitted to the National Centre for Biotechnology Information (NCBI) and dedicated to the nation and global community of cattle researchers.
Figure: Workflow to generate reference grade genome assemblies using trio-binning approach. Statistics of the resultant assemblies are mentioned in the table.
3. Validation of DBT-NIAB SNP chip for breed identification and preliminary genome-wide association studies of milk yield
In this project “Genomics for conservation of indigenous cattle breeds and for enhancing milk yield”, a high density SNPchip (DBT-NIAB-HDchip) was developed that is predicted to truly represent our indigenous breeds. To establish the proof of principle, this chip needs to be validated on our phenotypically purebred herds. In this venture, NIAB will be collaborating with National Dairy Development Board (NDDB); National Dairy Research Institute (NDRI), Karnal; GADVASU, Ludhiana; Lam farm, AP ; etc. NDDB approximately has 1000 animals each of Kankrej and Gir ; and 600 animals of Sahiwal, recorded for milk production. About 400 more Sahiwal, and 500 each of Tharparkar and Ongole will be obtained from the herds available at NDRI, GADVASU, Lam farm etc. Parallelly, genetic potential of indigenous breeds vis – a – vis milk yield will be taken up on a preliminary basis. The genotypes obtained from the chip can be used along with phenotype records available at different centers in different breeds to conduct Genome wide association studies (GWAS) and as well be used for imputation by NDDB.
Figure: A graphical representation of the research activities in the project. The activities highlighted in red will be ones in which I will actively participate and contribute.
4. Developing de novo genome assemblies of milch breeds of cattle i.e. Kankrej, Tharparkar, Red Sindhi, Sahiwal and Gir
The goal of this project is to characterise the genomes of indigenous milch breeds. Thus, a low-cost de-novo assembly using artificial long reads generated using linked-reads technology is proposed in the study. Linked-read libraries will be constructed using the 10X chromium platform, which will be used for NGS data generation. The data will be assembled using the Supernova assembler, which will produce phased, whole genome de-novo assemblies. Genome assemblies of five milch breeds, i.e. Gir, Sahiwal, Kankrej, Tharparkar and Red Sindhi will be constructed. Each draft de novo genome will be further assembled using a reference assembly for comparative analysis and annotation. The ultimate aim of the study is to detect small and large structural variations (SVs) and extract genotypic variations that generally cannot be captured by SNPs, such as large-scale chromosomal rearrangements.
Figure: Workflow to develop de-novo genome assemblies of indigenous cattle breeds.
5. Advancing the Indian Cattle Pangenome: Characterizing Non-Reference Sequences in Bos indicus
India, with the world’s largest cattle population having more than 50 registered breeds of Bos indicus, stands as a vital reservoir of genetic diversity with a select few designated as dairy breeds. However, the abundant diversity among Indian cattle breeds highlights the inadequacy of relying on the single reference sequence to represent the entire genomic content of desi cattle. We recognize the need to capture the genomic differences within the Bos indicus population as a whole, and specifically within the dairy cattle subset by identifying non-reference sequences and constructing pangenome.
Figure: Identification and characterization of Non-reference Unique Insertions (NUIs) in Bos Indicus.The flowchart illustrates the systematic process for identifying the NUIs. The diagram outlines the sequential steps involved in the selection and refinement of NUIs.
6. Identification of key molecular factors involved in resistance/susceptibility to paratuberculosis infection in indigenous breeds of cows
Mycobacterium avium subspecies paratuberculosis (MAP), the cause of Johne’s disease (JD), is endemic in domestic livestock (cows, buffaloes, goats, sheep etc.). JD is chronic, insidious and incurable in nature, results in granulomatous enteritis, leading to diarrhea, progressive weight loss and wasting, emaciation and death. It leads to high morbidity leading to huge economic losses due to reduced productivity, premature culling, increased veterinary costs, increased susceptibility etc. Early detection of infection and removal by culling,segregation and vaccination of infected animals are some of the technologies used to control the disease. However, cows cannot be culled in India for religious reasons.To unravel the host cell factors responsible for imparting resistance/ susceptibility to MAP infection, genome wide profiling of host genes using RNAseq and SNPs analysis will help to identify cows with potentially higher resistance for retention and multiplication for breeding purposes.
Figure: Comprehensive Overview of the Study, presenting objectives and methodologies to delineate the molecular landscape of MAP infection in indigenous cattle
7. Exploring Leptospira genomes for phylogenetic analysis and vaccine candidate
Leptospirosis is an emerging zoonotic and neglected disease across the world, causing huge loss of life and economic hardship. In nature, Leptospira species can be classified as pathogenic, intermediate, or saprophytic. This study proposes to perform comparative genomics on completely sequenced, publicly available Leptospira genomes in order to characterize all of its lineages and their virulence profiles. Differentiating strains of Leptospira species and providing insight into the taxonomic and evolutionary positions of genomes that need to be modified or reclassified are all part of phylogenomic characterisation. The extensive analysis focuses on core genome, pan genome, mobilome associated genes, and the entire virulome annotation. Finally, the study will provide a virulence profile of Leptospira for each species. The study also attempts to group clade-specific genes. Clade-specific and virulent genes can be used as markers in novel Leptospira isolates to define clade and related virulence levels. Wet-lab validation of virulent genes will aid in correctly targeting Leptospira pathogenic pathways and reducing leptospirosis. The project also intends to use reverse vaccinology approaches to find suitable vaccine candidates. The candidates will be chosen based on their immunological characteristics. These candidates will be employed in the development of a Multi-Epitope Vaccine (MEV). MEV design, In Silico characterization, and optimization will be the precursor to wet lab validation. A successful MEV will be a future vaccine and will help in controlling leptospirosis.
Figure: Graphical Abstract of phylogenomic analyses, genomic characterizations and virulence factor profiling of Leptospira.
Top Selected Publications:
1. Azam, S., Parthasarathy, S., Singh, C., Kumar, S. and Siddavattam, D., 2019. Genome organization and adaptive potential of archetypal organophosphate degrading Sphingobium fuliginis ATCC 27551. Genome biology and evolution, 11(9), pp.2557-2562.
2. Parthasarathy S, Azam S, Lakshman Sagar A, Narasimha Rao, et. al. 2017. Genome-guided insights reveal organophosphate-degrading Brevundimonas diminuta as Sphingopyxis wildii and define its versatile metabolic capabilities and environmental adaptations. Genome Biology and Evolution 9(1):77-81.
3. Faisal SM, Varma VP, Subathra M, Azam S, et. al. 2016. Leptospira surface adhesin (Lsa21) induces Toll like receptor 2 and 4 mediated inflammatory responses in macrophages. Scientific Reports 6:39530.
4. Azam S., Rao SB, Jakka P, Narasimha Rao V, Bhargavi B, Gupta VK, Radhakrishnan G. 2016. Genetic characterization and comparative genome analysis of Brucella melitensis isolates from India. International Journal of Genomics 2016:3034756.
5. Angela WH, Sharma M, Thatcher LF, Azam S, Hane JK., et al. 2016. Comparative genomics and prediction of conditionally dispensable sequences in legume–infecting Fusarium oxysporum formae speciales facilitates identification of candidate effectors. BMC Genomics 17:191.
6. Sinha P, Pazhamala LT, Singh VK, Saxena RK, Krishnamurthy L, Azam S., et al. 2015. Identification and validation of selected universal stress protein domain containing drought-responsive genes in pigeonpea (Cajanus cajan L.). Frontiers in Plant Science 6:1065.
7. Jaganathan D, Thudi M, Kale S, Azam S, et al. 2014. Genotyping-by-sequencing based intra-specific genetic map refines a ‘‘QTL-hotspot” region for drought tolerance in chickpea. Molecular Genetics and Genomics 290(2):559-71.
8. Kudapa H, Azam S, Sharpe AG, et al. 2014. Comprehensive transcriptome assembly of chickpea (Cicer arietinum) using Sanger and Next Generation Sequencing platforms: Development and applications. PLoS One 9(1):86039.
9. Azam S, Rathore A, Shah T, et al. 2013. ISMU: Integrated SNP mining and utilization pipeline for accelerated breeding. PLoS One 9(7):e101754.
10. Varshney RK, Song C, Saxena RK, Azam S, et al. 2013. Draft genome sequence of chickpea (Cicer arietinum) provides a resource for trait improvement. Nature Biotechnology 13(3):240-6.
11. Varshney RK, Chen W, Li Y, Bharti AK, Saxena RK, Schlueter, JA, Gonoghue MTA, Azam S, et al. 2012. Draft genome sequence of pigeonpea (Cajanus cajan), an orphan legume crop of resource-poor farmers. Nature Biotechnology 30:83–9.
Current Members:
Mr. Abhisek Sahu
Project associate-I
Research Interests: Genome assembly, WGS analysis, Comparative genomics, pan genomics, Transcriptome analysis
Alumni:
Ms. Sumaiya Khatun
Ms. Krutideepa Rout
Mr. Ashish Pratim Mahanta
Ms. Rutvi Rajpara
Mr. Lokesh Kumar
Mr. Naveen Kumar Pandey
Ms. Lakshmi S Prasad
1. Role of Investigator: Co-I
Title of the Project: Genomics for conservation of indigenous cattle breeds and for enhancing milk yield, Phase-I
Funding Agency: DBT
Period/Duration: 2017-2020
2. Role of Investigator: PI
Title of the Project: Identification of key molecular factors involved in resistance/susceptibility to paratuberculosis infection in indigenous breeds of cows
Funding Agency: DBT
Period/Duration: 2020-2023
3. Role of Investigator: Co-PI
Title of the Project: Validation of DBT-NIAB SNP chip for breed identification and preliminary genome-wide association studies of milk yield
Funding Agency: DBT
Period/Duration: 2021-2024
Genomics and Computational Biology Laboratory, NIAB
National Institute of Animal Biotechnology
Survey No. 37, Opp. Journalist Colony
Extended Q City Road, Near Gowlidoddy
Gachibowli, Hyderabad
Telangana – 500032
Email: sarwar[at]niab[dot]org[dot]in
Tel: +91-(0)40-2312-0134
1. Development of largest cattle HD SNP chip INDIGAU
2. Haplotype resolved Bos indicus Genome assembly
Tharparkar: https://www.ncbi.nlm.nih.gov/datasets/genome/GCA_029378745.1
Sahiwal: https://www.ncbi.nlm.nih.gov/datasets/genome/GCA_029378735.1
3. Google scholar profile:
https://scholar.google.com/citations?user=Lxi0CHAAAAAJ&hl=en
Positions will be advertised on the NIAB website (www.niab.res.in). Please refer to the website for updates on available positions.
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