**3. Next generation sequencing for drug discovery**

Next generation sequencing (NGS) is the term used for massive parallel sequencing experiments that can be conducted using DNA, RNA, or miRNA. NGS has revolutionized clinical and research studies by enabling sequencing of whole human genomes within a single day.

This powerful NGS can be used in several different areas. For example, NGS can be used in clinical settings for identifying genetic variants with high specificity and sensibility, thus allowing for detection of mosaic mutations that could not be previously identified by Sanger sequencing [162]. In the field of microbiology, NGS can be used for identifying and characterizing pathogens, including novel strains or mutants, thereby allowing for linking a pathogen or a new pathogenic strain to an outbreak in a specific region or to a particular individual(s) [163]. The role of NGS in the field of oncology is quite significant, as this technology can be used for pursuing personalized medicine, in particular for developing targeted therapies for specific cancers correlated with individual genetic profiles of patients. Moreover, NGS is highly useful for diagnosis, and for classification of different types of cancer in both adults and children [162, 164, 165].

Furthermore, NGS is highly versatile, primarily for the diversity of analysis that can be undertaken, as well as to numbers and types of biological samples that can be analyzed. A listing of major types of analyses that can be undertaken, as well as of types of biological samples used in NGS are presented in **Table 2**.


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**Figure 4.**

*Microarrays and NGS for Drug Discovery DOI: http://dx.doi.org/10.5772/intechopen.96657*

**3.1 Target identification**

could be of particular use are presented in **Figure 4**.

in turn could be used for target identification [169].

targets for specialized treatments/therapies [172, 173].

*Various steps involved in drug discovery whereby NGS can be of particular benefit.*

biomarker discovery, identification of biopharmaceuticals, drug resistance, and vaccine discovery [166–168]. Those steps involved in drug discovery where NGS

In recent years, NGS has been valuable in the identification of different genetic alterations of a pathogen/pathology that can be useful for targeted treatment. The versatility of NGS allows for evaluating genomic regions using genomic analysis, transcriptomics, RNAseq, and miRNA seq in order to identify gene(s) and their regulation(s)/functionality(ies) in response to different disease conditions, which

Analysis of genetic variant(s) is yet another important approach for identifying mutations in rare diseases, as these could then be used for treatment of such target(s) [170, 171]. Epigenetic studies, such as methylation analysis or CHIP-seq analysis, known to be altered in different pathologies, could also aid in identifying

NGS has been widely used for gene to target identification for treatment of cancer. As it is well known, the National Comprehensive Cancer Network (NCCN) has several guidelines for NGS target identification used for treatment of various types of cancer. These include targeting genes for lung cancer (*EGFR, ALK, ROS1, BRAF*, and *PDL1*) [174], colorectal cancer (*NRAS/HRAS/KRAS, BRAF*, *HER2*, *MLH1, MSH2, MSH6,* and *PMS2*) [175], breast and ovarian cancers (*BRCA1/2, TP53, STK11, PTEN, CDH1, PALB2*, among others) [176]. By identifying mutations in each of these genes, clinicians are able to treat patients with specific targeted treatments. In Waldenström's macroglobulinemia, NGS has been employed in evaluating genomic variations that could better inform treatment of patients, and that would ultimately lead to better outcomes. It is observed that patients with recurrent somatic mutations in genes of myeloid differentiation factor 88 (*MYD88*) and chemokine receptor type 4 (*CXCR4*) demonstrate different responses to the same treatment, and thus these genes serve as clinical determinants of clinical

As for drug discovery, NGS has been successfully used in various areas of drug discovery, beginning with target identification, compound screening,

#### **Table 2.**

*Types of NGS analysis, purpose(s), and biological samples used.*

biomarker discovery, identification of biopharmaceuticals, drug resistance, and vaccine discovery [166–168]. Those steps involved in drug discovery where NGS could be of particular use are presented in **Figure 4**.
