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Dr. Sekar is currently Principal Scientist at Genentech and directs a state-of-the-art DNA sequencing laboratory (both Sanger and Nextgen machines) at Genentech that serves all of Genentech Research.

Dr Sekar is a leading expert in the area of Cancer research, genomics and sequencing, having authored and co-authored over forty articles in peer-reviewed journal including Science and Nature. His laboratory has been at the forefront of understanding underlying genetic changes in cancer genomes through systematic identification of somatic mutations in large number of cancers types and subtypes using a number of techniques including next-generation sequencing. His laboratory is also involved in developing diagnostic and prognostic markers to enable personalized cancer therapy.

Dr. Samir Brahmachari received a PhD in Molecular Biophysics from the Indian Institute of Science, Bangalore in 1978. He has shown exemplary scientific leadership and has made contribution in the area of Functional Genomics with special emphasis on molecular genetics of neurological and psychiatric disorders and functional Genomics.

Prof. Brahmachari has demonstrated the structural flexibility of DNA and the role of repetitive sequences in DNA transactions much before the discovery of repeats association with genetic disorders. He has made major contributions in molecular analysis of genetic disorders associated with trinucleotide amplification and repetitive sequence instability. Using a combination of structural biology, computational genomics and population based polymorphism scanning he and his group have provided a novel structural frame work for understanding the etiology of several neurological disorders. He was first to establish a close clinical network to address genetics of complex disorders and demonstrated association of two genes to Schizophrenia and Bipolar Disorder (synaptogyrin 1 and MLC1 gene) and identified several SNPs and other markers associated to various neurological disorders.

Prof. Brahmachari and coworkers have carried out extensive computational analysis of the repetitive sequences in the genome and were one of the first to propose functional role of such sequence. He and his associates have developed novel and unique tools for genome annotation and identification of functional signature for hypothetical proteins in the genome through comparative genomics approach. A recent finding of Prof. Brahmachari and his associates are that the human miRNA can target critical genes in HIV, preventing HIV proliferation. This has received wide international recognition. (Petit-Zeeman, S. Nature Rev. Drug Discovery, 2006, 5.5).

Dr. George holds a Ph.D. in Biochemistry from the Indian Institute of Science, Bangalore. He did his postdoctoral research at the National Institutes of Health, Bethesda, MD, USA prior to returning to India as the head of the Molecular Biology Division at SPIC Science Foundation in Chennai.

Dr. George is a recipient of the National Science Talent Scholarship (NCERT) and Fogarty International Fellowships. Among his many notable achievements is a paper in Nature during his PhD from IISc where he published the organization and bidirectional transcription nature of H2A, H2B and H4 histone genes in rice embryos. Dr. George has also made extensive contribution in the plant biotechnology area including development of insect resistant rice and tobacco, engineering salt tolerance in crops and other technologies for genetic engineering of crop plants. Further Dr. George was instrumental in several successful grant applications during his academic tenure.

He is a member on several educational, technology and advisory boards.

Dr. VL Ramprasad joined SciGenom labs after 5 years of work at Spinco Biotech, India handling Affymetrix and Illumina technologies. Prior to this he has worked as a Senior Scientist at Vision Research Foundation, Sankara Nethralaya, Chennai. Here he worked on the genetics of inherited ophthalmic diseases.

He has a Masters degree and PhD from BITS, PILANI, India. He has 15 peer reviewed publications to his credit.

View publications:

• NCBI : www.ncbi.nlm.nih.gov/pubmed/?term=Vedam+Ramprasad

Dr. Mitali Mukerji, a senior scientist at the Institute of Genomics and Integrative Biology works in the broad area of Genomics and Molecular Medicine. Dr. Mitali discovered the role of DNA hairpin in regulation of cryptic operon in E.coli during her doctoral research at the Indian Institute of Science in Bangalore. At IGIB, she has been instrumental in the setting up the genomics initiative and has made important contributions in the area of population genomics, hereditary ataxias and role of repetitive sequence in genome organization and function. All of her projects primarily aim at identifying informative and predictive markers for disease predisposition. Her group has provided insights into the mechanism and origin of triplet repeat expansion in hereditary ataxias and identified founders for different ataxias like SCA1, SCA2, SCA3 and SCA12 in the Indian population. Her group has also carried out extensive genome wide informatics analysis of primate specific Alu repeats in human and have demonstrated how these elements could create novel regulatory networks in human. She has also demonstrated how this basal data can be used for dissecting disease genes, identifying signatures of selection, tracing mutational histories and also for pharmacogenomics studies. Presently, she has concerted her efforts at integrating genomics with principles of Ayurveda, an ancient system of predictive and personalized medicine and initiated a new field of Ayurgenomics. She heads a newly formed CSIR's Ayurgenomics Unit "TRISUTRA" at IGIB.

Zora Modrusan is a Senior Scientist in the department of Molecular Biology at Genentech. She joined Genentech in 2004 and throughout the years she managed a core laboratory that provides a full suite of genomic technologies, including microarrays and Next Generation Sequencing technology, in support of the company’s research effort towards drug discovery and development. Prior to Genentech, Zora worked for several years as a Scientist at Incyte Genomics, a company that provided an integrated platform of genomic technologies designed to help in the understanding of the molecular basis of disease. Before Incyte Genomics, Zora was a Group Leader at the start-up company ID Biomedical, Vancouver where she managed a product development team working on gene-based bacterial diagnostics. Zora also completed two years of an industrial postdoctoral fellowship at ID Biomedical. She holds a Ph.D. in plant molecular genetics from the University of British Columbia, Vancouver and a B.Sc. and M.Sc. in biology from the University of Zagreb, Croatia.

Dr. Ishwar Verma completed his medical undergraduate degree in Amritsar Medical College and went on receive training in pediatrics and genetics training in England. After becoming a member of the London College of Physicians, he joined the All India Institute of Medical Sciences in 1967 and became Professor of Pediatrics and Head of the Genetics Unit. Dr. Verma received his genetics training from various places, including the University of Zurich, Boston Massachusetts General Hospital, and National Institutes of Health in USA.

Dr. Verma currently heads the Department of Genetics Medicine at the Sri Ganga Ram Hospital, New Delhi. He is interested in topics such as fetal medicine, reproductive genetics, genetic counseling and prenatal diagnosis. He has worked on the health problems of Indian tribal communities and is the Editor-in-Chief of the Indian Journal of Pediatrics.

Profile, Coming Soon.

The major research interest of Dr. Thangaraj's group includes: origin of modern human; genetic basis of - male infertility, cardiovascular disease, sex determination, mitochondrial disorders, ayur genomics; and forensic genetics. Their finding about the origin of Andamanese is a major breakthrough in the field of origin of modern human (Current Biology, 2003; Science, 2005, Nature, 2009). Their Recent finding suggests that about 60 million people in South Asia, approximately 1% of the world populations, are at risk for sudden cardiac arrest (Nat. Genet. 2009). We have mapped a region on the X-chromosome responsible for male sex determination (J. Clin. Endocrinol. Metabol, 2006). Their extensive study on male infertility has provided the genetic basis of male infertility in Indian populations and also established the association of mitochondrial DNA variations with several disorders (J. Androl, 2003; Am.J. Med. Genet, 2006; Mitochondrion, 2010).

Dr. Andrew Peterson received a PhD in Genetics from Harvard University and was a post-doctoral fellow in the Department of Physiology at the University of California, San Francisco (UCSF). He became Assistant Professor of Genetics at the Duke University Medical Center and went on be Assistant Professor in Residence at the UCSF Department of Neurology before working at the Ernest Gallo Clinic and Research Center as a Principal Investigator. Currently, he is the Senior Director of Molecular Biology in Genentech.

About his research focus, Dr. Peterson says "We have primarily been using neural development as our biological paradigm for these investigations, but are beginning to branch out into metabolism. In addition to the largely postdoctoral based efforts of my own lab, I am very involved in a number of projects in Molecular Biology that are also based in murine genetics."

Dr. Sidhu received his PhD in Biochemistry from the Simon Fraser University, Burnaby, BC and did his post-doctoral work in Genentech Inc. USA. He is currently an Associate Professor at Banting and Best Department of Medical Research in the University of Toronto. The Sidhu Lab focuses on synthetic antibodies and Fab libraries, peptide-binding modules, and protein structure and function. His studies have helped develop better antibodies for unmet medical needs. Dr. Sidhu's recent publications include "T cell receptor-like recognition of tumor in vivo by synthetic antibody fragment" in PLoS One (2012) and "Conformational Control of the Ste5 Scaffold Protein Insulates Against MAP Kinase Misactivation" in Science (2012).

Sridhar Sivasubbu's laboratory is interested in exploiting the advantages of zebrafish to dissect molecular mechanisms of gene function, regulation and genome organization in vertebrates. Recent research activities include deciphering non-coding RNA mediated regulation of blood and blood vessel development, transposon-mediated gene trapping and development of zebrafish models for application in personalized and precision medicine in humans. His group is actively involved in mapping the genome and transcriptome of the wild zebrafish. His group was also responsible for the whole genome sequencing of human samples from India, Srilanka and Malaysia.

Sridhar did his PhD from M.S University, Tirunelveli, India and postdoctoral research at the Center for Cellular and Molecular Biology, India and the University of Minnesota, USA. He is a faculty at the CSIR-Institute of Genomics & Integrative Biology since 2006. He was also the scientific head of The Center for Genomic Application, a Public-Private partnership company established by IGIB for enabling research in the field of Genomics and Proteomics.

Profile, Coming Soon.

Mallika Singh completed her early schooling and her B.S. in Delhi, graduating from St. Stephen's college at the University of Delhi. She then moved to the US and received her Ph.D. in biochemistry from the University of Utah, where she worked on fundamental mechanisms of mutagenesis that drive genomic instability in yeast and cancer in mammals. She then went on to post-doctoral work at the University of California at San Francisco focused on complex cancer models, examining drivers of tumor angiogenesis and telomerase expression in genetically engineered mouse cancer models. Since then, she has held lab head positions at three Bay are biotechnology companies, including her current position as a research investigator at the Novartis Institutes for Biomedical Research working on preclinical mouse models of cancer with an emphasis on translational research and oncology drug development.

Dr. Samir Brahmachari received a PhD in Molecular Biophysics from the Indian Institute of Science, Bangalore in 1978. He has shown exemplary scientific leadership and has made contribution in the area of Functional Genomics with special emphasis on molecular genetics of neurological and psychiatric disorders and functional Genomics.

Prof. Brahmachari has demonstrated the structural flexibility of DNA and the role of repetitive sequences in DNA transactions much before the discovery of repeats association with genetic disorders. He has made major contributions in molecular analysis of genetic disorders associated with trinucleotide amplification and repetitive sequence instability. Using a combination of structural biology, computational genomics and population based polymorphism scanning he and his group have provided a novel structural frame work for understanding the etiology of several neurological disorders. He was first to establish a close clinical network to address genetics of complex disorders and demonstrated association of two genes to Schizophrenia and Bipolar Disorder (synaptogyrin 1 and MLC1 gene) and identified several SNPs and other markers associated to various neurological disorders.

Prof. Brahmachari and coworkers have carried out extensive computational analysis of the repetitive sequences in the genome and were one of the first to propose functional role of such sequence. He and his associates have developed novel and unique tools for genome annotation and identification of functional signature for hypothetical proteins in the genome through comparative genomics approach. A recent finding of Prof. Brahmachari and his associates are that the human miRNA can target critical genes in HIV, preventing HIV proliferation. This has received wide international recognition. (Petit-Zeeman, S. Nature Rev. Drug Discovery, 2006, 5.5).

Dr. Stephan Schuster graduated with a PhD in Biochemistry from the Max-Planck-Institute of Technology and did post-doctoral research at the Division of Biology at the California Institute of Technology. After a successful post-doctoral stint, he returned to assume several teaching and research positions at the Max-Planck-Institute of Biochemistry, Developmental Biology and Ludwig-Maximilians-University in Germany. He joined the Department of Biochemistry and Molecular Biology, Pennsylvania State University as Associate Professor and has been full Professor there for the last three years. He serves as member of the Center for Comparative Genomics and Bioinformatics, Institute of Molecular Evolutionary Genetics as well as Center for Infectious Disease Dynamics at Pennsylvania State University. He is also conjoint Professor of Faculty of Medicine at University of New South Wales, Australia. His research work focuses on a wide range of evolutionary topics to explore genetic diversity of natural populations. His group sequenced the whole nuclear genome of the extinct woolly mammoth and has subsequently unraveled sequences of several different organisms. His work has won several awards and accolades including Science magazine's Breakthrough of the Year in 2006 (runner up) and 2008 (top 10), Time Magazine's Top Ten Scientific Discoveries in 2008, and was among Time Magazine's top 100 most influential people of 2009 with W. Miller. His current area of research focuses on extinction genomics, human genomics, microbial genomics, metagenomics, and bioinformatics.

Dr. Stephen Turner founded Pacific Biosciences (formerly Nanofluidics) and secured its Series A funding in 2004. He was awarded a Ph.D. in Physics by Cornell University in 2000, where he worked with Prof. Harold Craighead to study the behavior of biomolecules in nano-fabricated structures. His work contributed to the establishment of the Nanotechnology Center at Cornell. He was a member of the project team at Cornell which developed the technology now employed by Pacific Biosciences and was co-author of the cover story in Science magazine (January 31, 2003) that introduced the technology to the scientific community. Dr. Turner's undergraduate work was at the University of Wisconsin, Madison, where he received a Bachelor of Science in Applied Mathematics, Electrical Engineering and Physics. He is the author of over 30 scientific papers in fields ranging from nanofluidics, genetics, cell attachment to chemically- and topographically- modified surfaces, x-ray lithography and process modeling. He is listed as the inventor on nine U.S. patents and more than 20 published patent applications. Dr. Turner was recipient of the MIT Technology Review "TR100" Award in 2003 and the University of Wisconsin Madison Distinguished Young Alumnus Award in 2008. He is a sitting member of the National Institutes of Health grant review study section on new technologies. He oversees the scientific and technical direction of Pacific Biosciences.

Dr. Rajesh Gokhale’s group is interested in understanding how metabolic networks are elaborately tuned in nature in three different model systems

Chemical Biology of Mycobacterium tuberculosis: His group is delineating metabolic pathways and mechanisms employed by Mycobacterium tuberculosis to generate molecular diversity that are crucial for its virulence and pathogenecity.

Dictyostelium discoideum Morphogenesis:Rajesh Gokhale’s group is investigating the role of polyketide synthases in understanding the complex differentiation process of Dictyostelium

Vitiligo: In this program, his group is investigating into the biochemical mechanisms underlying melanocyte-keratinocyte interactions in context of vitiligo.

Dr Boone's lab is focused on the development and application of functional genomics techniques to a number of biological problems.

Donnelly Centre, Banting and Best Department of Medical Research, Department of Molecular Genetics, University of Toronto, Toronto, Canada

Profile, Coming Soon.

Dr Ahmed graduated in Veterinary Medicine in 1995 (Nagpur) and obtained further degrees in Animal Biotechnology (MS) (NDRI, Karnal) and a PhD (Manipal University) in Molecular Infectious Diseases. He worked at CDFD in Hyderabad as Staff Scientist and Group Leader during 1998 -2008. In December 2008 Dr Ahmed joined the University of Hyderabad as Associate Professor of Biotechnology. Current research interests of his group include genomics, evolution and molecularpathogenesis of the two co-evolved human pathogens, namely, Mycobacterium tuberculosisand Helicobacter pylori, in the context of evolution of adaptation mechanisms, and acquisition and optimization of virulence during colonization/infection. Dr Ahmed also has interest in comparative genomics of bacterial pathogens obtained from different epidemics as well as single patients at different occasions and this approach nurtures the idea of 'chronological evolution' and 'replicative genomics' as tools to study host-microbe interaction over time. In 2009, Dr Ahmed initiated a new and vibrant group/laboratory at the University of Hyderabad which currently encompasses 16 full time PhD students and 2 post doctoral fellows and also supports an Indo-German International Research Training Group on Functional Molecular Infection Epidemiology

Dr N K Sing's group is working on different aspects of structural, functional and comparative genomics with special emphasis on rice, wheat, pigeonpea, tomato and Rhizobium. The group has successfully completed the sequencing rice chromosome 11, tomato chromosome 5 and complete genome of chickpea Rhizobium M. ciceri Ca181. Presently, working on finishing of tomato and M. ciceri genomes and production sequenincg of pigeonpea genome. This sequence information will be used for the identification of agriculturally important genes in tomato. They are now mapping genes for yield and quality traits in rice, wheat and pigeonpea by using SSR and SNP markers. Besides, also working on high resolution mapping of salinity tolerance genes in rice and molecular tagging and map-based cloning of genes for aroma and linear kernel elongation in Basmati rice and development of high density reference map in pigeonpea.

Profile, Coming Soon.

Dr. Ashoktaru Barat is the Director of The Directorate of Coldwater Fisheries Research, a premier research institute of Indian Council of Agricultural Research for the coldwater fisheries and aquaculture in the country is working towards the development of coldwater fisheries sector in India.

Dr. K VijayRaghavan is the Secretary of Department of Biotechnolgy (DBT), India. Prof. VijayRaghavan was formerly distinguished professor and Director of the National Centre for Biological Sciences (NCBS), Bangalore, which is a part of the Tata Institute of Fundamental Research. He was conferred the honour of the Padma Shri by the Govt. of India on 26th January, 2013. He is also a recipient of the Infosys Prize in the life sciences category in 2009. He is also a recipient of the prestigious Shanti Swarup Bhatnagar Award (1998).

He graduated with a Bachelor of Technology degree in Chemical Engineering from IIT Kanpur in 1975.He completed his doctoral work in 1983 in the field of Molecular Biology and holds a Ph.D from the Tata Institute of Fundamental Research. During his post-doctoral work, from 1984 to 1985, he was a Research Fellow and then, from 1986 to 1988, a Senior Research Fellow at the California Institute of Technology.

Ravi Gupta is working as Senior Bioinformatics Scientist at SciGenom Pvt. Ltd. heading the bioinformatics operation of the company. His current interests include several areas of computational genomics including whole genome and transcriptome analysis, plant genomics, clinical genome sequencing and high-performance computing.

He received his PhD in the area of bioinformatics from Computer Science & Engineering department of IIT Roorkee. He worked as faculty for short time at Anna University – KBC research center, Chennai. For his post-doctoral work, he moved to Wistar Institute, USA, Computational & Systems biology, where he work with Dr. Ramana Davuluri in the area of computation genomics. In less than three years he was promoted to staff scientist of the Wistar Institute. During his post-doctoral work he worked in wide area of computational and cancer genomics. He has developed several pipeline and frameworks for data analysis and integration of NGS wide-variety of data including ChIP-seq, RNA-seq, and small RNA-seq. He has also developed integrative program for mammalian promoter prediction and databases – MPromDb, MDevTrDb.

Emily Niemitz obtained her Ph.D. from the Human Genetics program at Johns Hopkins University under the supervision of Andy Feinberg, where she studied epigenetic and genetic alterations associated with the Beckwith-Wiedemann syndrome and related disorders. She joined theNature Genetics team in 2004.

Diane received her BS in Biochemistry from the University of Texas at Austin and her PhD in Biochemistry from Arizona State University. She has been with Illumina for almost 7 years and currently manages the global Miseq business.

Dr. Lakshmi Mahadevan obtained her Ph.D in Biotechnology from Rajiv Gandhi Centre for Biotechnology, Trivandrum. She has about 9 years experience in various areas of molecular biology, gene cloning, tissue culture and genetic engineering. Prior to joining SciGenom Labs, she has held academic positions in reputed institutions. She has been working as a Genomics Scientist in MedGenome, the molecular diagnostics division of SciGenom, for over 2 years wherein she has been involved in the MedGenome’s genetic testing process which includes Sanger sequencing, Realtime PCR analysis and Next Generation sequencing technologies. Apart from leading the lab team at MedGenome, she has been engaged in the development and optimization of new assays, validation of test results and generation of reports.

There are almost 4,000 known genetic diseases which affect 3-9% of children. Next generation sequencing has made possible, for the first time, genome-based differential diagnosis of all of these diseases in a single test. Over the past 3 years we have used these methods to test over 500 children with likely genetic diseases. I will discuss our methods, diagnostic yield and case reports.

Mithun (Bos frontalis) is a unique bovine species of North Eastern Hill Region of India. Mithun is basically a meat animal like beef cattle and is efficient to convert grass, forages, and various by-products, into highly nutritious and tasty meat which is a delicacy for the tribal population of NEH region.

Moreover, the mithun holds a unique place in evolution vis a vis with other bovines, and there has been limited data about its phylogenetic position. At present, there is very little genetic information for the mithun, which is an essential tool for detailed understanding of the biology of this unique species.

Recently, de novo draft assembly of few mammalian genomes including cattle (Liu et al., 2009), sheep (Archibald et al. 2010), horse (Bright et al. 2009) and giant panda (Li et al., 2010) was completed. The ability to generate and assemble a draft sequence for an entire mammalian genome using next-generation sequencing technology indicates that such technology can be used to generate many more mammalian genome draft sequences in a rapid and cost-effective manner.

Next-generation sequencing (NGS) technologies have been recently used for whole genome sequencing and for re-sequencing projects of different livestock species where the genomes of several specimens are sequenced to discover large numbers of single nucleotide polymorphisms (SNPs) for exploring within-species diversity, constructing haplotype maps and performing genome-wide association studies (GWAS).

Whole genome sequencing of mithun will be a very important research work in the field of livestock genomics where a very unique livestock species will be explored with whole genome studies with immense possibilities for the future and advanced research in many areas, including large scale re-sequencing, whole genome association studies (WGA), transcriptome sequencing, messenger RNA and microRNA expression profiling, and DNA methylation studies.

Mithun is the only species of livestock for which no draft genome sequence is available so far and there is enormous opportunity to explore the genome of this species to generate valuable information.

The present study was taken up to fill up this gap in this species and to generate and assemble a draft genome sequence for the mithun (Bos frontalis) through next generation sequencing platforms.

Next-generation sequencing (NGS) technologies provide a revolutionary tool with numerous applications. The power of NGS technologies to address diverse biological questions has already been demonstrated in many studies. Here, I illustrate the use of NGS technologies in generation of genomic resources for a non-model species taking example of crop plant chickpea. Chickpea is an important crop legume plant not only for its high nutritional value, but also for its ability to maintain soil fertility by fixing atmospheric nitrogen. The availability of limited genomic resources and very low levels of genetic diversity has been an important constraint in chickpea improvement. We sequenced the transcriptomes of cultivated (desi and kabuli) and wild chickpea using NGS technologies and generated optimized assemblies to reveal the gene space. The comprehensive functional annotation identified genes involved in various cellular processes and transcription factor encoding genes. We performed global gene expression a nalysis also to identify genes expressed in tissue-specific manner. In addition, several genetic variations (simple sequence repeats and single nucleotide polymorphisms) among the cultivated and wild chickpea have been identified. Many of these variations were found to be present in the tissue-specific and transcription factor encoding transcripts. We have sequenced and analyzed the chickpea genome sequence also to reveal gene space, gene expression and genetic variations. More recently, we analyzed the global transcriptome dynamics using RNA-seq to identify novel genes/pathways involved in chickpea flower development. Efforts have also been made to identify microRNAs from different tissues in chickpea via deep sequencing to gain insights into the regulatory aspects of various developmental processes. These genomic resources will surely facilitate research in various areas of functional and applied genomics in chickpea for crop improvement.

The MiSeq personal sequencing system enables researchers to go from sample to analyzed data with a simple end to end workflow and unmatched accuracy. MiSeq is the only next-generation sequencer that integrates amplification, sequencing, and data analysis in a single instrument. The MiSeq system leverages Illumina’s proven TruSeq® sequencing by synthesis chemistry, making it the ideal platform for any lab performing rapid and cost-effective genetic analysis. Researchers and organizations worldwide are adopting the MiSeq for a wide range of applications.

Aakrosh Ratan is a Research Associate in the Department of Biology of the Pennsylvania State University. He received his Ph. D. in Computer Science from Penn State in 2009, and held the Huck Institute Fellowship in Genomics at Penn State from 2010-2012. His primary research interest is in algorithms for comparative genomics to understand the genome variation and genetic diversity in various species. In particular, he is interested in studying DNA from threatened and extinct species to understand the biology of extinction, using a combination of next-generation sequencing and ancient DNA techniques.

Genome-wide assessments of genetic diversity provide a powerful analytical tool that informs of the similarities, differences, origins and the evolutionary history of a species. There are established pipelines and software to identify single-nucleotide variants in species such as humans, i.e. where we have a reference haploid genome of high quality. But, for a significant fraction of the species (and this is almost always true for threatened and extinct species), we lack a representative genome sequence. I will talk about methods to study diversity that can be used in such cases, and highlight some of our work in this area. An increased knowledge of the genomes of endangered species will be beneficial in population evaluation, to identify risk factors for genetic disorders, and provide insights into demographic management of small populations, both in the wild and in captivity.

The last year has seen rapid expansion of the application spaces in which Pacific Bioscience’s SMRT sequencing provides unparalleled performance in the field. As the readlength has doubled again in the last 9 months, users are moving beyond bacterial genomes into much larger genomes ranging from fungi to plants to human genomes. The last year has also seen widespread deployment of HGAP and Quiver, algorithms that can provide de novo assemblies with consensus accuracy 100 times better than any other new-generation sequencing system. Together, these advances have positioned SMRT sequencing to provide valuable insights unavailable to any other system in a range of applications, from analysis of disease outbreaks to genome structural variations in cancer. I’ll highlight five research areas where SMRT sequencing should be universally adopted and end with a few predictions of where we will be in the coming months.

Whole genome sequencing of Purple puttu, exhibiting purple/red colour in almost all visible plant organs except in nodes and pollen, was performed using the Illumina HiSeq platform with the objective of understanding the genetic compliment of the anthocyanin pathway leading to purple/red colour phenotype as well as other agronomically useful traits associated with stress responses. In all, a total of 215,201,508 short reads of 76bp paired-end (~43.5 Gb) were generated. The trimmed reads were mapped to the Nipponbare genome (MSU6 assembly) using BWA program with default settings. Overall, 90.6% of the total reads aligned to the Nipponbare genome and 84.27% of the total aligned reads were of good quality. 94.18% of the whole genome was covered with an average depth of 30X.

We found a total of 3,056,572 SNPs and 442,514 short InDels between Purple puttu (indica) and Nipponbare (japonica) genome, 83% of the SNPs are homozygous changes, whereas in the case of Indels, 90% are homozygous changes. The majority of the Indels detected were shorter than 5bp. Variant annotation was performed using VariMAT program based on gene annotations present at plant Ensembl database. Annotation was also performed against known QTL and SSR regions of the genome provided by Gramene database. Of the total variants identified, 34.2% of SNPs and 28.7% of InDels fall inside the gene region. Only 15% of the SNPs and 4.7% of the InDels identified overlap the coding region of the gene. Among the coding SNPs, 60% are of non-synonymous changes, which include 10,551 non-sense variants. A large number of variants were detected in retrotransposons, MYB genes, NB-ARC domain containing genes, NBS-LRR disease resistance genes. Variants falling in the anthocyanin pathway genes were studied in detail with the aim of understanding the molecular mechanisms underlying the regulation of the colour phenotype. We also analyzed variants overlapping with genes related to response to drought, salinity, cold and submergence. A detailed comparative genomics analysis of more than 60 different rice varieties, land races, and several wild varieties such as nivara, barthii, glaberrima, rufipogon was performed and the results will be discussed.

Tumor mutation panel sequencing using NGS technology is a targeted approach to sequence regions of interest in the tumor genome at high depth. This multi-gene, cost-effective analysis for tumor mutations will enable personalized treatment by matching the patient with the appropriate drug based on the mutational profile and thus aid in effective risk management and treatment procedures.

We used this method to test DNA isolated from FFPE tumor tissue for mutations in a set of 26 selected genes amplified as 175 amplicons (hotspots). The libraries were sequenced to >7,000X depth on Illumina Miseq platform. The sequence generated was analyzed to identify variants using Ilumina Miseq somatic variant caller as well as in-house developed alignment and variant calling/annotation tools. Clinically relevant and actionable mutations were annotated using published variants in literature and clinical databases. The annotation was also done using Medgenome’s proprietary somatic mutation database tool OncoMDTM. Selected variant calls were validated using orthogonal technology like Sanger sequencing or Realtime PCR.

Dr. K.VijayRaghavan Abstract, Coming Soon.

NGS has been shown to be a powerful technology for cancer genome studies because it reveals the entire landscape of the genomic aberrations underlying the complex cellular mechanisms that drive cancer development. We have built a high-throughput, state-of-the-art NGS lab that focuses on NGS applications for cancer genome profiling at the transcriptome, exome and whole genome level. To perform cancer genome NGS studies, we first developed and implemented an efficient laboratory process flow starting with the quality control of input samples and finishing with the quality control of generated data. In addition to using a variety of analytical instruments and Agilent’s Bravo workstation robotics for managing NGS library construction, we have put in place a supporting infrastructure for managing and analyzing NGS data from large genomic studies. Improved exome sequencing and RNA-seq workflows, as well as exceptional Illumina based sequencing capability, enabled the completion of multiple cancer genome studies, including profiling of colon cancer and small cell lung cancer (SCLC). Our analyses of colon and SCLC cancers led to the identification of a number of previously unreported genomic aberrations including single nucleotide variants, indels, gene amplifications and translocations. Some of the identified cancer-type specific lesions likely serve as driver genes and their functional significance has been further investigated. By advancing NGS applications and utilizing them for similar genomic studies, we hope to contribute towards better understanding of underlying causes and mechanisms of cancer.

The Genetic center at SGRH provides genetic counseling to over 4000 patients from all over India every year. A substantial proportion of these cases have intellectual disability, with or without brain or systemic malformations, seizures, and neurodegenerative disorders; while other cases have neuromuscular and other single gene disorders like deafness and retinitis pigmentosa. The patients seek precise diagnosis for ending their diagnostic odyssey, starting a therapeutic journey, to obtain information regarding prognosis and anticipatory guidance, and for determining the risk of recurrence, and prenatal diagnosis in future pregnancies.

For a substantial number of families we are able to make a precise diagnosis using conventional laboratory investigations of biochemistry, radiology, tandem mass spectrometry, and microarrays. However, a significant number of patients remain undiagnosed. In 40 such cases we evaluated the utility of NGS, either using targeted gene panels or exome sequencing to decipher the diagnosis. A precise diagnosis was achieved in 22 (55%) cases. This high success rate was achieved due to good clinical assessment which enabled the choice of the appropriate panel or technology.

Targeted gene sequencing (TGS) was used to identify the gene involved, in cases where the phenotype could result from mutations in many genes. For example, in three cases of AR Retinitis Pigmentosa TGS revealed the specific gene harboring the mutations in two cases, while in one case a mutation was identified in only one allele. In a case of xeroderma pigmentosum with developmental delay homozygous novel mutation was observed in the ERCCS gene. In two brothers with developmental delay, macrocephaly and raised lactate a hemizygous single base pair insertion in KDM5C was observed, confirming a diagnosis of Claes-Jensen syndrome. In a case of suspected Leigh's disease mutation was recognized in PLA2G6 gene, confirming a diagnosis of neuroaxonal dystrophy. TGS in two cases of hereditary spastic paraplegia from the same community revealed identical mutations, representing a possible founder mutation, while in one case of primary microcephaly, and two cases of Seckel syndrome mutations were identified in ASPM , MRE11A, and CENPJ genes respectively.

Exome sequencing revealed new genes in four cases – mutations in SCO2 gene in a familial case of malignant hyperthermia, in ELOV4 gene in a Sjogren Larsson-like syndrome, WNT1 mutations in a family with moderately severe recessive osteogenesis imperfecta, and in a case of leukoencephalopathy, hypomyelination with brain stem and spinal cord involvement mutations in DARS gene. In a couple having multiple babies with polydactyly and other malformations exome sequencing revealed two heterozygous mutations in LRP2 gene, thus extending the phenotype of Donnai Barrow syndrome, as polydactyly has never been described in this syndrome. In a undiagnosed case of muscle disease mutations were observed in GNE gene (inclusion body myopathy), with the possibility of therapy with sialic acid analogues.

Targeted gene sequencing and exome sequencing represent powerful tools to help a medical geneticist to find the causative gene. However, good clinical knowledge of the topic is required to choose the best panel of genes or technology, and to interpret the data obtained. These newer technologies will change the future practice of medical genetics and molecular diagnostics.

Next generation sequencing (NGS) has revolutionised the field of Human genetics. Whole genomes and complete exomes can be sequenced in as less as 7 days time, producing millions of different output reads which can then be pieced together and mapped to the genome. Targeted sequencing of PCR amplicons/regions of interest from specific genes produce millions of copies of the same output read. This attributes to the very high sensitivity of this technique and allows the detection of very low levels of point mutations amongst WT reads. The huge cost advantage and rapid TAT for sequencing the genomes has made the NGS technology creep into medical practice with specific reference to Oncology and pediatric care. It has ushered what we call as Personalized medicine.

Improved sequencing technologies demonstrated that NGS is a mature tool for clinical sequencing for identifying mutations. This presentation describes the oppurtunities and also various challenges that we face in clinical sequencing using NGS. The presentation gives snippets of a sequencing study done at MedGenome which proves that germline variants missed by traditional Sanger sequencing can be detected by NGS and gives new insights into the disease biology.

The talk will describe the use of Next Generation Sequencing to identify causative variants in Rare Disease instances where typically only a couple of affected individuals are available for sequencing. We will focus on the core challenge, i.e., that of starting with a large number of variants and distilling down to a very small number of candidates, very quickly. The talk will describe all the methods we have been developing at Strand towards this goal, and illustrate these methods in the context of real Clinical cases in India.

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Over the last decade, therapeutic monoclonal antibodies represent one of the major breakthroughs for the treatment of cancer and other diseases. To date, most therapeutic antibodies have been obtained by the humanization of rodent-derived antibodies, but in recent years, research in antibody engineering has given rise to a new wave of technologies that promise to transform the field. Phage-displayed libraries of “synthetic antibodies” use entirely man-made antigen-binding sites and thus circumvent the need for natural immune repertoires. Using in vitro selections, highly functional antibodies with fully human frameworks can be generated against virtually any antigen in a matter of weeks. We have developed simple synthetic antibodies that use a single human framework and limited chemical diversity in restricted regions of the antigen-binding site. Moreover, the use of synthetically designed libraries enables the use of alternative scaffolds for applications beyond the reach of the antibody framework. In particular, we have designed libraries of ubiquitin variants that can be used to inhibit or activiate virtually any of the hundreds of ligase and deubiquitinating enzymes in the ubiquitin system. These ubiquitin variants are adapted for intracelluar function, and thus, they can be introduced into cells to probe function in a living cellular context. In addition, we have developed small, optimized scaffolds that function like antibodies but are amenable to full chemical synthesis, thus enabling the incorporation of non-natural amino acids. The power of the technology has been demonstrated by the development of potent protein inhibitors composed entirely of D-amino acids. In sum, these advances in the design of synthetic binding proteins extend the applications for affinity reagents well beyond the range of natural antibodies and this should have a transformative effect on many areas of biological research.

Fish and humans are separated by a few million years of evolutionary time. Yet they have a remarkable similarity in the architecture and functioning of their genes and genomes. This remarkable evolutionary conservation has allowed one to use the zebrafish as a model to understand human biological processes. The ability to sequence human genome in relatively modest setups and costs is generating a deluge of data at the level of individual human/patients. The art and science of interpreting this information is the next major hurdle in the personalized and precision medicine space. Zebrafish with its arsenal of genomic tools has the potential for becoming a key model for accessing biological significance of genomic sequence variations and lesions. We will report our progress in the sequencing human and zebrafish genomes and our efforts towards building tools for annotating functionally relevant variations with the aim to develop a proof of concept for personalized medicine. We will also provide a framework f or integrating the human genetic information in zebrafish models for interpreting the genome information for optimal prevention and treatment in humans.

Improved efforts are necessary to define the functional product of cancer mutations currently being revealed through large-scale sequencing efforts. Using genome-scale pooled shRNA screening technology, we mapped negative genetic interactions across a set of isogenic cancer cell lines and confirmed hundreds of these interactions in orthogonal co-culture competition assays to generate a high-confidence genetic interaction network of differentially essential or DiE genes. The network uncovered examples of conserved genetic interactions, densely connected functional modules derived from comparative genomics with model systems data, functions for uncharacterized genes in the human genome, and targetable vulnerabilities. Finally, we demonstrate a general applicability of DiE gene signatures in determining genetic dependencies of other non-isogenic cancer cell lines. For example, the PTEN-/- DiE genes reveal a signature that can preferentially classify PTEN-dependent genotypes across a series of non-isogenic cell lines derived from breast, pancreas and ovarian cancers. Our reference network suggests that many cancer vulnerabilities remain to be discovered through systematic derivation of a network of differentially essential genes in an isogenic cancer cell model.

This talk will focus on preclinical modeling of response to targeted therapies in a variety of mouse models of human cancer, ranging from simple xenografts to sophisticated genetically engineered mice and patient-derived tumor models. Case studies will be presented to discuss the translatability of findings in these models to therapeutic response and resistance in the clinic.

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The bacterial genomic information has enhanced systems level understanding of bacterial physiology giving insights into perturbed metabolic interactions. The cross-talk between altered metabolic pathways and chemico-cellular changes in the cell leads to adaptive physiological functions. The challenge at this stage is to combine NGS analysis, both genomic and transcriptomic that can reveal biology of the organism. Our group has revealed mechanistic and regulatory interactions which culminate into biological outputs like community morphogenesis of Mycobacteria and its adaptation into novel intracellular niches to establish extra- pulmonary forms of infection. In this talk, I will provide perspective on the two aspects of chemico-cellular rewiring in Mycobacteria.

We are constructing a genome-scale genetic interaction map, examining all ~18 million gene-gene pairs for synthetic genetic interactions, which has generated quantitative genetic interaction profiles for ~75% of all genes in the budding yeast, Saccharomyces cerevisiae. A network based on these profiles reveals a functional map of the cell in which genes of similar biological processes cluster together in coherent subsets and highly correlated profiles delineate specific pathways to define gene function. Most recently, we’ve been focussing on the essential gene network, mapping genetic interactions for conditional temperature sensitive alleles of essential genes. The resultant global network identifies functional cross-connections between all bioprocesses, mapping a cellular wiring diagram of pleiotropy. Genetic interaction degree correlated with a number of different gene attributes, which may be informative about genetic network hubs in other organisms. Large-scale genetic interaction mapping in human cancer cells carrying defined mutations revealed networks resembling the yeast network and identifies potential drug targets for synthetic lethal cancer therapies.

DNA topoisomerases are among the most highly conserved proteins known. They have key functions in resolving superhelical strains caused to DNA during processes such as replication, recombination and chromosomal segregation. However, a role in gene regulation, especially in the context of cell-fate specification during development, remains poorly understood. We find that the expression of topo II isoforms, topoisomerase IIα (TOP2α) and topoisomerase IIβ (TOP2β), is the characteristic of dividing and postmitotic tissues, respectively. Topoisomerase IIα and IIβ preferentially bind to gene promoters in embryonic stem (ES) cells and postmitotic neurons respectively that are defined by an active chromatin state. Common targets of TOP2α and TOP2β are housekeeping genes, while unique targets are involved in proliferation/pluripotency and neurogenesis, respectively. TOP2α activity further confers a set of developmental genes an accessible chromatin state in ES cells, possibly as a prerequisite for their activation and occupancy by TOP2β upon differentiation. TOP2β is recruited to gene promoters at a time when cells exit cell cycle during neurogenesis and the target genes are activated. Absence of TOP2α activity affects pluripotency and differentiation potential of ES cells while TOP2β deficiency does not impair stem cell properties and early steps of neuronal differentiation but causes premature death of postmitotic neurons. These defects result primarily from misregulation in the expression of topo II target genes in the respective stage of differentiation. These findings reveal a distinct division of labor between the topo II isoforms during development and show how, by contributing to the gene regulatory program, TOP2α and TOP2β define the identity of proliferating, pluripotent and postmitotic, terminally differentiated cells, respectively.

With the advent of massively parallel, Next-Generation Sequencing (NGS) technologies, the scientific community is confronted by the challenge of data handling, management and heralding sustainable and testable ideas out of the genomic information. Bacterial genomes although small could provide larger insights into their adaptation and evolution within a human host or the niches thereof. We are involved with sequencing the genomes of pathogenic species and strains of Escherichia coli, Helicobacter pylori, Mycobacterium tuberculosis, Salmonella enterica, and Vibrio parahaemolyticus etc. for some time and these genomes are analyzed for dissecting various survival mechanisms based on mining and characterization of novel genes and functions. Extensive genome sequence analyses and comparative genomics enabled us delineate global diversity and genomic plasticity of the classical and chronic human pathogens such as H. pylori and M. tuberculosis. Moreover, these analyses helped us identify several putative virulence encoding genes in M. tuberculosis and H. pylori. Some of these virulence factors possibly play crucial roles relevant in chronic persistence of the bacteria and provide them with survival advantages. Further, we analyzed the signaling pathways pertaining to proapoptotic and or proinflammatory behavior of these virulence factors from H. pylori and pathogenic mycobacteria. In the former organism, many of the putative virulence factors are encoded by the ‘plasticity region cluster’ of the genome and we looked at functions of select proteins therein. In M. tuberculosis, we studied novel members of the dos-regulon that have regulatory and innate immune functions. Given these observations, it can be concluded that large scale genome sequence based insights could facilitate identification of new genes/functions and improved understanding of the vertices and boundaries of bacterial parasitism in health and in disease, in single hosts and in the communities.

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Successful marker-assisted backcross breeding in crops that needs introgression from ill-adapted lines to elite lines could be achieved in the following way: (1) region around the gene of interest should be saturated with markers that will help in identifying finer recombinants through background selection in the carrier chromosome(s), and (2) the foreground selection marker should preferably be from the candidate gene. Oilseed mustard (Brassica juncea) is one such crop which requires precise marker-assisted introgression of several quality traits (two genes for low erucic acid, 4 genes for low glucosinolates and two genes for yellow seed coat colour) from ill-adapted east European lines to Indian cultivars. Conventional backcross breeding or marker-assisted backcross breeding only through foreground selection for the introgression of these traits has been largely unsuccessful because of retention of large fragment of donor genome around the gene of interest leading to linkage drag in near-isogenic lines.

The new advancements in the areas of genomics particularly NGS technology and genome sequencing are going to offer unprecedented opportunities to fulfil some of the above impediments particularly saturating the target regions and identification of causal gene(s) underlying the trait even in the recalcitrant genome like B. juncea. We have earlier mapped genes controlling seed glucosinolates and erucic acid by candidate gene approach. The seed coat colour trait earlier mapped by anonymous SSR markers has now been mapped by candidate genes. Although these traits have been introgreessed from east European line to Indian variety by maker-assisted backcross breeding following foreground selection, all these near-isogenic lines are inferior to their wild type counterpart in yield and yield components due to retention of large areas of donor genomes around the genes of interest. Hence, it was realized that a saturated map of the target regions would be helpful to identify finer recombinants for further elimination of the linkage drag. To fulfil this objective, a SNP-based genome map and target region saturation maps by SNP markers were developed through the use of the RNA-seq data generated in the lab using Illumina paired-end sequencing technology. A saturated map thus developed will now be used for further reducing the linkage drag around the introgressed genes.

Now a day’s gene discovery through whole transcriptome profile has been adopted worldwide as it is less expensive and very easy to analysis. The gradual updating in fast sequencing and subsequently bioinformatics analysis made possible to go deep into the life processes and its evolution. Transcriptome profiles of several fish species are also being available now in different molecular databases including few Indian teleostean fishes. In the present study, we tried to obtain a set of immune related genes in snow trout, Schizothorax richardsonii; an endemic species of Himalayas. The population of the species is declining in nature due to both biotic and abiotic stress. Since the species is not widely used in culture system scanty information are available on its health management. Therefore, in an intention to get a basket of immune responsive genes we challenged the fish with Aeromonas hydrophilla, very commonly available fish pathogens in many water bodies. Initially, we have developed a reference data base of liver transcriptome of this non model organism using denovo analysis of paired end sequencing of cDNA library in Illumina Hiseq 2000. The GO annotation had shown highest similarities with the gene data bases of Danio rerio and other fish species. Few genes like interleukin-1β, interleukin 6, interleukin 17, interferon induced transmembrane protein 1, MHC class I antigen etc are observed to be highly over expressed ranging from 4.8 to 32 folds and few MHC class I, Cytochrome P450, immunoglobulin Z heavy chain etc are among low expressed (0.0 to 1.8 fold ) genes in comparison to control. This reference database will be useful for analysis in gene discoveries in several coldwater fish species in the region.

•   Complete NGS system covering complete process from primary sample preparation to biological interpretation of sequencing data
•   Flexibility to run flow cells whenever needed, combined with continuous load and total sample scalability
•   Best standardization with automation of workflow
•   Workflow directly linked with primary NGS data processing and biological interpretation of sequencing data

The QIAGEN GeneReader™ Sample to Insight workflow provides a streamlined and integrated approach to next-generation sequencing (NGS), from sample preparation to the biological interpretation of sequencing data.

The majority of the GeneReader Sample to Insight workflow is automated, ensuring greater standardization and more accurate results. Preanalytic sample preparation can be done with either the QIAcube® or QIAsymphony®, apart from the target enrichment step, which utilizes an easy to use and fast approach for amplification of tens to hundreds of genes of interest in a highly multiplexed PCR. A single molecule amplification process for clonal amplification, which is fully automated on a dedicated QIAcube NGS system, processes multiple, clonally-amplified libraries in a single workday before loading the libraries on flow cell of the GeneReader.

The QIAGEN GeneReader benchtop sequencer is at the core of the workflow, and offers unprecedented scalability and flexibility in an NGS instrument. Highly accurate and cost-effective, proven sequencing-by-synthesis chemistry, along with its unique ability to process up to 20 flow cells in parallel through an innovative turntable design, make the GeneReader a scalable NGS system that can grow with increasing throughput needs. Additionally, the continuous loading mode of the GeneReader allows researchers to add additional flow cells during an ongoing run, significantly decreasing the overall turnaround time for projects that require multiple flow cells.

Each GeneReader is supplied with a software suite for comprehensive data analysis. Following its acquisition of Ingenuity® Systems, QIAGEN is employing market-leading NGS data interpretation by integrating cloud-based Variant Analysis™ software into GeneRead enrichment panels to enable the rapid translation of raw sequencing data into actionable results.

Illumina has been at the forefront in introducing innovative tools for genomics researchers. Illumina’s technology has been increasingly used to identify, and select for, desirable traits that lead to more productive livestock and healthier animals. This talk will focus on the genomic solutions that Illumina offers- from cost-effective sequencing of whole genomes to screening for single nucleotide polymorphisms (SNPs). Some examples, taken from the literature, of the use of Illumina’s technology to breed disease resistant animals using array genotyping and the characterization of pathogens using whole genome sequencing will also be presented.