Novel DNA sequencing techniques that researchers currently use for sequencing the whole genome, exploring genome diversity, epigenetics, metagenomics, discovery of complex and non-coding RNA structures, protein binding sites, and the gene-expression profiling by RNA sequencing is known as “next generation” sequencing (NGS). NGS finds its applications in genetics, virology, microbiology, and pathology.
Today, NGS is being used for whole genome sequencing of viruses, determination of genome variability of viruses, the evolution of viral pathogens within their respective hosts. It has shed new light on the genome of the influenza virus, host interaction of the human immunodeficiency virus (HIV), and human hepatitis C viruses. It has opened new avenues for the discovery of novel disease-causing viruses, including oncoviruses. It has provided a standard healthy human virome for direct comparison with the diseased viromes. Apart from human diseases, NGS plays a key role in the understanding of mutations, their importance in evolution and unfurling the mysteries of human adaptation since ancient times. It has the power to answer the mysteries of ancient human migration and the spatiotemporal courses taken by the human genetic variants.
How does NGS help in the discovery of mutations?
NGS has made whole genome sequencing of humans entirely feasible and cost-efficient. Whether it is the determination of a sporadic mutation, a single nucleotide polymorphism (SNP) or an INDEL (insertion and deletion) mutation in the sample genome, it is easy to determine the precise nature and location of the same.
The Human Genome Project has made the entire human DNA sequence available on the web for any user. NCBI stores the gene sequences in the GenBank complete with the sequences of known genes and their proteins. As of November 2002, the HGP has successfully identified over 3 million variations in the human genome known as the SNPs, and it has generated full-length complementary DNAs.
NGS data analysis software has not only helped researches locate genetic variants within the human genome, but it has made the comparative study of the genomic variation between two different species entirely possible.
How does NGS help in the study of mutations and cancer?
Not all mutations that occur in the human genome are lethal or pathogenic. Sadly, some of them pose a high threat of causing cancer in the later years, like the mutations in BRCA1 and BRCA2 genes that increase the risk of breast cancer and ovarian cancer in women.
Certain familial cancer types like Familial Adenomatous Polyposis (FAP), Lynch Syndrome, Cowden Syndrome, and Li-Fraumeni Syndrome can be passed down from one generation to the next. While a history of cancer in the family is not enough for the oncologist to diagnose someone with cancer, some types of cancers like the ones mentioned above are hardly the results of de novo mutations.
The presence of NGS data analysis software allows the oncologists or diagnosticians to run detailed comparative sequencing of a person’s genes of interest (the genes specifically identified in tumorigenesis and oncogenesis). NGS can also locate one or multiple mutations in the germline cells that can pass onto the next generation. NGS has made it possible for doctors to predict certain familial cancers in patients even before they occur, and it facilitates the early detection of cancers that improve patient prognosis.
How has NGS made the real-time pathogen surveillance system a possibility?
The Zika and Ebola epidemics in certain areas around the globe have established the necessity of almost real-time diagnosis, continuous surveillance, and uninterrupted tracking of the disease progression. Pathogen surveillance is only complete when the complete genome sequencing of the pathogen is available. The inclusion of NGS in the genomic diagnostics and epidemiology of the disease has made the rise of an open, global, and digital surveillance system a possibility in the near future.
In most of the areas affected by such endemic diseases, the presence of a laboratory capacity is rare. In such cases, the presence of a wholesome genomics-based approach can improve public health. NGS can strengthen the overall health of a community by powering the One Health approach, which considers the health of humans, animals, and the environment to be connected. NGS can function as the glue for the multi-sectoral trans-disciplinary approach to health and pathogen surveillance system.
How can NGS demystify evolution and adaptation processes in multiple species?
In the last couple of decades, the data on the human genome as grown expansively. With a majority of the information available for public use, the research on human genetics has grown tremendously as well. The genomic data of more than 1100 archaic hominin and ancient human species now available, the studies on ancient human evolution has gained a new impetus.
Researchers can now use the data sets from the DNA and genetic samples collected from numerous ancient humans. It will offer them new perspectives to the evolution and adaptation mechanisms of the ancient hominin and humans to changing the environment, lifestyle, and pathogen-host interactions. The analyses of discovered genetic material from the archaic hominin can provide the researchers with new information about the early pathogens and their co-evolution with the host species.
Similar whole genome sequencing for the contemporary plant and domesticated animal species can give them new insights to their early adaptation to a domesticated life at the hands of the early humans. It can shed new light on human evolution and the consequences of the same on human behavior. The use of NGS data analysis software not only expedites the entire process, but it increases the accuracy and precision as well.
NGS is no longer an isolated process that can only sequence the whole genome from human and other samples. It is a high throughput technique that can produce huge volumes of DNA and genomic data for further comparative analyses. It is the integrated tool that several fields leverage to make the best use of the genetic information, genomic data, DNA specimen, and archeological samples the researchers have recovered. It has made the studies on virology, oncogenes, mutations, evolution and evolutionary consequences deeper, and more informative than ever before.