Category: Genomics

Categories
CRISPR Genomics

Exploring the Potential of RNA Editing with CRISPR-Cas13 in Treating Genetic Diseases

Farbod Azaripour Masooleh—McMaster Life Sciences 2025

Gene Editing has been a frequently discussed topic with its increasing importance, as new technologies continue to improve it. CRISPR is one such gene editing technique that has revolutionized the field by making it more precise and easier. This has made scientists hopeful about the possibility of correcting disease-causing genes to prevent genetic disorders. The VI CRISPR-Cas effector, Cas13b, targets designated RNAs directly. The combination of Cas13b and ADAR2 adenosine deaminase domain with rational protein engineering has resulted in a more efficient enzyme. This has made efficient and specific RNA depletion of mammalian cells possible. This system is known as RNA Editing for Programmable A to I Replacement (REPAIR). This system can edit full-length transcripts carrying pathogenic mutations, not limited to specific sequences. To minimize the system and facilitate viral delivery, REPAIR is being modified to increase its specificity. This gives scientists a reliable RNA-editing platform with broad applicability for research studies, therapeutics, and biotechnology advancements. To test this system in humans, REPAIRv1 was developed to correct disease-causing G→A mutations in nucleotides.

Figure 1: measuring the flexibility of the sequences for editing RNA using REPAIRv1. SOURCE: Science

Substantial editing was achieved at 33 sites with an efficiency rate of 28%. The REPAIR system enables multiplex editing of multiple disease-causing variants. The dCas13b platform, designed for programmable RNA binding, can also be used for live transcript imaging, splicing modification, targeted localization of transcripts, RNA-binding protein pulldown, and epitranscriptomic modifications.

Figure 2: This image shows the use and effect of REPAIRv1 on repairing a G→A mutation. SOURCE: Science

The base conversions that scientists are able to achieve by using REPAIR are restricted to using adenosine in order to create inosine. But, combining dCas13 with other RNA editing domains, can help with editing cytidine to uridine. In addition, for relaxing the substrate preference so that cytidine can be targeted, mutagenesis of ADAR can be used. This grants more specificity from the duplexed RNA substrate requirement so that it can aid C to U editors.

In conclusion, as technology advances, the equipment used for scientific purposes gets more precise and accurate. CRISPR, as one such tool, holds great promise for curing genetic diseases and improving millions of lives in the near future.

References

Cox DB, Gootenberg JS, Abudayyeh OO, Franklin B, Kellner MJ, Joung J, et al. RNA editing    …..with CRISPR-CAS13. Science. 2017Nov24;358(6366):1019–27.

Categories
CRISPR Genomics Precision Medicine

The Future of Designer Babies and Genomic Editing

Kahono Hirasawa—McMaster Health Sciences 2026

You may have come across the term designer babies in recent years as the topic has started to rise in popularity. Although they may sound like babies who cruise around town in their Gucci baby stroller, snuggled up in their Louis Vuitton onesie, the reality is much more fascinating. Unfortunately, however, many still need to be made aware of the actual science, methods, and implications of the development of designer babies and how we may already be seeing the application of this technology all around us. 

The idea of designer babies was initially proposed to reduce or avoid heritable diseases coded by mutations in our DNA, creating healthy and happier babies (1). This process is done by editing the genome through methods such as preimplantation genetic diagnosis or genetic modification (1). 

SOURCE: inviTRA

Preimplantation genetic diagnosis (PGD) is the process of genetic testing of an embryo before it is implanted in the uterus and is used in conjunction with in vitro fertilization (IVF) (2). PGD identifies potential genetic abnormalities in embryos before embryo transfer (implanting a newly formed embryo into the woman’s uterus), commonly used to prevent single-gene conditions such as cystic fibrosis or sickle cell anemia (3). For example, in sickle cell anemia, a single allele point mutation can be targeted. However, more complex conditions such as autism involve the interaction of many genes and the environment and cannot be targeted or even understood as thoroughly. Despite this, PGD is available for all inherited conditions where the exact mutation is known and can be tested on the embryo (3). 

The possibilities with PGD are still in development, and although the technique still suffers from limitations, it is a practical and more sensible approach to reducing heritable diseases.

However, the idea of the designer baby in popular culture has taken a new meaning and often refers to the use of genomic editing technologies for purposes beyond simply reducing heritable disease (1). Unlike PGD, the topic of gene editing in humans is an ever-changing debate on the ethics, morality, and beliefs regarding this technology’s political and social implications. Nevertheless, individuals have already begun creating babies with edited genomes and engineered mutations (4).

Individuals may take advantage of this technology to create babies with certain facial features and physical characteristics such as coloured eyes, athletic builds, and taller bodies. However, using genomic editing to create babies with “ideal” features strongly reinforces stereotypes and prejudice against people with features that are not considered a high priority for gene editing. Thus, the use of this technology poses various questions regarding its safety, ethics, and social implications. Furthermore, as this technology is in the early stages of development, it is likely that access to this resource will come at a high cost and will not benefit individuals who lack the necessary finances to support such procedures, widening the gap between the socioeconomic classes seen throughout society.             A highly controversial use of genome editing is demonstrated when human genomes are altered using technologies such as CRISPR-Cas9 (6). CRISPR-Cas9 involves genome editing that may be used to make changes to genes in egg or sperm cells or to the genes of an embryo that could be passed to future generations. This application of genome editing raises the previously mentioned ethical concern of passing down enhanced human traits such as height or intelligence and the possible issues with the safety of such technique. In addition, it is possible that the use of CRISPR-Cas9 may produce “off-target” effects and can damage the genome in unpredictable ways.

SOURCE: The Scientist

Currently, genomic editing is conducted using genome editing tools to alter or destroy mutated mitochondrial DNA (1). In the embryo, thousands of copies of mitochondrial DNA (mtDNA) are present in the cell’s cytoplasm, which is highly prone to mutations (1). A high enough concentration of mutated mtDNA will lead to the development of mitochondrial diseases, which genomic editing hopes to reduce. This application of genome editing is widely accepted throughout the scientific community; however, it still comes with risks.      

Thus, the creation of designer babies remains in the early stages of development. Although there have been many significant advances in genetic editing and modification in recent decades, the topic still causes many to question if it should even exist and the ethical controversies it proposes (5). 

References

  1. Pang T.K. Ronald, Ho, P.C. Pang. Designer Babies [Internet]. 2016;26(2): 59-60. Obstetrics, Gynaecology & Reproductive Medicine. Available from: https://doi.org/10.1016/j.ogrm.2015.11.011
  2. Resnik Robert. Preimplantation Genetic Diagnosis: Molecular Genetic Technology. [Internet]. Creasy and Resnik’s Maternal-Fetal Medicine: Principles and Practice. 2019. Available from: https://www.sciencedirect.com/topics/medicine-and-dentistry/preimplantation-genetic-diagnosis
  3. UCSF Health. Pre-Implantation Genetic Diagnosis [Internet]. The Regents of The University of California. Available from: https://www.ucsfhealth.org/treatments/pre-implantation-genetic-diagnosis
  4. Cyranoski, David. The CRISPR-baby scandal: what’s next for human gene-editing [Internet]. Nature. 2019. Available from: https://www.nature.com/articles/d41586-019-00673-1
  5. Ly, Sarah. Ethic of Designer Babies [Internet]. The Embryo Project Encyclopedia; 2011. Available from: https://embryo.asu.edu/pages/ethics-designer-babies
  6. Medline Plus. What are genome editing and CRISPR-Cas9? [Internet]. National Library of Medicine. 2022. Available from: https://medlineplus.gov/genetics/understanding/genomicresearch/genomeediting/
Categories
AI Genomics Proteins

Unlocking the Secrets of Proteins with Alphafold2: A Breakthrough in Bioinformatics

Rubani Suri—McMaster Health Sciences 2026

The word “protein” has an ever-changing definition throughout our lives. As children, we often unknowingly consume protein in the form of nuggets or hamburgers. As we reach adolescence, proteins often appear on food guides and in our biology classes through the form of polypeptides and amino acids. However, not until the recent developments of AlphaFold2 Artificial Intelligence have proteins been defined as a complex three-dimensional network of amino acid residues.

To understand the significance of AlphaFold2, we must first understand the “protein folding problem.” Three-dimensional proteins are more than amino acid chains and are known for having multiple side chains on their structure. These side chains have the capacity of interacting with one another, creating configurational changes to the structure of the protein. As a result, it becomes nearly impossible to determine the structure of a three-dimensional protein due to side chain complexities (1).

That’s where AlphaFold2 comes in.

Using the power of Artificial Intelligence (AI), AlphaFold2 has mastered the technique of homology modeling: using evolutionary history to find proteins with known structure that are genetically similar to the “target protein,” and use them to deduce structural similarities with the target protein (2). Using comprehensive databases, AlphaFold2 uses AI to predict target protein structure through the following steps (3):

  1. The input sequence (genome of target protein) is inputted
  2. Multiple Sequence Alignments (MSAs), which are amino acid sequences that share evolutionary similarities with the target protein, are inputted into Alpha Fold machinery to create predictions for the structure based on evolutionary relatedness
  3. Protein database structures, which are similar in structure to the target, are also used as templates for target protein structures
  4. The input sequence is paired with itself in a matrix to produce an array of numbers that represents all the potential pairs of amino acid sequences in the target protein.
  5. The pair representations are put into “EvoFormer” technology, which collates all this data to analyze relationships between individual amino acids, to gain an understanding of the structures that specific amino acids would form when bonded to one another
  6. These predicted relationships are then put through a Structure Module technology, which builds a geometric protein model.
  7. This protein model is then analyzed, and the rotation and angle of each amino acid is calculated, creating a three-dimensional protein model.
  8. Side chains are predicted using a technology that detects ‘chi angles’ (angles between intersecting planes) on the three-dimensional residue structure.
  9. The bond lengths and angles are finalized by running the final structure through a relaxation step, which removes any inconsistencies within the protein structure.
  10. The final accuracy is then improved by running the predicted protein chain through the network three times more.
  11. Along with the predicted structure, the Alpha Fold technology creates two confidence matrices which provides a ‘confidence score’ for each angle between the residues by analyzing the predicted error in the predicted structure.

Figure 1. SOURCE: AlphaFold Protein Structure Database

Figure 1 depicts a structural prediction for a target protein once all the steps above are complete. The protein depicted in Figure 1 is hemoglobin, a globular transport protein found in erythrocytes.

Figure II. SOURCE: AlphaFold Protein Structure Database

Figure II depicts the confidence score of Hemoglobin, as determined in step 11 of the process shown above.

Although in its developmental stages, AlphaFold2 is a technological advancement that has the capacity to revolutionize both the pharmaceutical and biochemical world. This innovation has been groundbreaking, especially for pharmaceutical companies. This has been crucial as they are interested in the structure prediction of allosteric sites where small molecules can bind to produce cell responses such as inflammation, itching, and pain. Understanding the structure of these protein binding sites will allow drug developers to create specific inhibitors for these binding sites, preventing small molecules from binding and creating a painful response (4). The understanding of binding site structure will allow for the possibility of “structure-based drug design” (4), a technique that is estimated to accelerate the research and development of drugs from “years to months” (4).

In conclusion, the publicly accessible nature of AlphaFold2 protein structure data allows drug development companies to have readily available protein information at their fingertips, accelerating drug development and efficacy. Through its continued success, AlphaFold2 has the ability to revolutionize the pharmacological world, allowing for the accessibility of effective, fast-acting medications around the world.

References

  1. Singh J. The history of the protein folding problem: A seventy year symbiotic relationship between… [Internet]. Medium. Medium; 2020 [cited 2022Nov27]. Available from: https://medium.com/@jaguarsingh/the-history-of-the-protein-folding-problem-a-seventy-year-symbiotic-relationship-between
  2. Alessia David Person Envelope Suhail Islam Evgeny Tankhi levich Michael J.E.Sternberg, Highlights AlphaFold, et al. The alphafold database of protein structures: A biologist’s guide [Internet]. Journal of Molecular Biology. Academic Press; 2021 [cited 2022Nov27]. Available from: https://www.sciencedirect.com/science/article/pii/S0022283621005738
  3. Callaway E. What’s next for alphafold and the AI protein-folding revolution [Internet]. Nature News. Nature Publishing Group; 2022 [cited 2022Nov27]. Available from: https://www.nature.com/articles/d41586-022-00997-5#:~:text=AlphaFold%20deploys%20deep%2Dlearning%20neural,the%20PDB%20and%20other%20databases.
  4. Mullard A. What does alphafold mean for drug discovery? [Internet]. Nature News. Nature Publishing Group; 2021 [cited 2022Nov27]. Available from: https://www.nature.com/articles/d41573-021-00161-0
Categories
Genomics Precision Medicine

How Modern Genomics has Changed our Approach to Cancer Treatment

Alexia Di Martino—McMaster University Molecular Biology & Genetics 2023

Within our chromosomes, there are billions of nucleotides that are all a part of our genome, the entirety of our DNA. Genomics is the study of the genome. A nucleotide sequence, its precise location, and the gene-gene or gene-protein interactions of specific genes are just a few of the findings that can be discovered through genomics.1 The human body is amazing in its ability to use DNA as a blueprint to direct millions of processes in the body. Of course, our DNA also encodes for the billions of other vital cells – like those of the blood, skin, and brain among other organs – that make up our body on a whole. When cell division goes wrong, though, cells may continue to divide uncontrollably and develop growths that we know as cancer.2

There are two families of genes that influence cancer development. The tumour suppressor gene family has a positive effect on cancerous growth when inactivated or improperly functioning. On the other hand, proto-oncogenes cause cancerous growth when they are mutated and active.3

The Human Genome Project was an advancement in sequencing technology that allowed for a decreased cost of sequencing an organism’s entire genome, as well as improved accuracy of the nucleotides and genes that are sequenced.4 Artificial intelligence and computer algorithms are even further advanced technologies that give researchers the ability to automate pattern-recognition within these sequences. From this, links between a gene’s function in the DNA compared to the patient’s phenotypic presentation of a disease can be made.

Tens of thousands of sequenced genetic mutations have been archived through the amazing work of oncology researchers into genetic libraries. One of these libraries is The Cancer Genome Atlas (TCGA).5 Using a patient’s genome, doctors can refer to these mutated cancer-linked genes to screen patients for susceptibility to a specific cancer.

SOURCE: British Columbia Genome Sciences Centre6

With the knowledge of the patient’s cancerous tumour’s genome, clinicians can identify the exact mechanisms of the cancer cells that causes their proliferation. By comparing the genome of the same patient’s normally functioning ‘germline’ cells to their cancer, researchers can pinpoint the mutated or defective genes responsible for the cancer. They can then recommend better-informed treatments such as pharmaceutical drugs and antibodies targeting certain molecules or pathways of the tumour cells.7 Targeted treatments are much better overall than uninformed therapies. Radiation therapy or stem cell transplants may not be appropriate or as effective in all cases, and can be very expensive. Understanding the genomics of a patient’s cancer could spare them from unnecessarily high medical bills, and more importantly, could have less harmful effects on their body, leading them to being cancer-free more quickly.8

While genomics-driven cancer treatment has been in practice in this way, recent studies into novel gene-editing practices have shown to be promising for the future. In the CRISPR-Cas9 gene editing system, scientists specially design a guide RNA to target a specific DNA fragment. When this guide RNA binds the gene of interest, it associates with a Cas enzyme that cleaves the DNA at that location.9 Scientists may insert a new gene in that cleavage site or perform other modifications depending on their goal.

SOURCE: National Cancer Institute9

Since at least 2017, researchers have been working on using CRISPR-Cas9 on model organisms such as mice and zebrafish in vitro to remove or directly target genes linked to cancer. However, it still poses some challenges when attempting to deliver cancer treatment in vivo.10 These issues are already being studied to create functional and safe delivery of CRISPR-Cas9 gene editing in different tissues in order to accommodate the wide range of cancers seen in patients. As the cancer genome library continues to expand, the CRISPR-Cas9 method of treatment will experience many benefits as well.

The work of biologists in all fields have contributed to this progress – from improved genetic sequencing techniques, to experiments that identify cancer genes, to the assembly of genetic libraries, and everything in between. These advances give every human being a lifesaving advantage in cancer diagnoses. With further research on these gene libraries, scientists will be able to screen the genomes of patients and target cancer-causing genes to inhibit their mechanisms before cancerous cells even get the chance to cause damage.

References

  1. NIH Staff. A brief guide to genomics [Internet]. Genome.gov. 2020 [cited 2022Jan2]. Available from: https://www.genome.gov/about-genomics/fact-sheets/A-Brief-Guide-to-Genomics
  2. Williams GH, Stoeber K. The cell cycle and cancer. The Journal of Pathology. 2011Oct12;226(2):352–64.
  3. Lee EY, Muller WJ. Oncogenes and tumor suppressor genes. Cold Spring Harbor Perspectives in Biology. 2010;2(10).
  4. Hofstatter EW, Bale AE. The promise and pitfalls of Genomics-Driven Cancer Medicine. AMA Journal of Ethics. 2013;15(8):681–6.
  5. NCI Staff. The cancer genome atlas program [Internet]. National Cancer Institute. 2019 [cited 2022Jan2]. Available from: https://www.cancer.gov/about-nci/organization/ccg/research/structural-genomics/tcga/history
  6. BCGSC Staff. Genome sequencing helps prioritize cancer treatment options [Internet]. Genome Sciences Centre. 2020 [cited 2022Jan2]. Available from: https://www.bcgsc.ca/news/genome-sequencing-helps-prioritize-cancer-treatment-options
  7. Mattick JS, Dziadek MA, Terrill BN, Kaplan W, Spigelman AD, Bowling FG, et al. The impact of genomics on the future of Medicine and Health. Medical Journal of Australia. 2014Jul7;201(1):17–20.
  8. Welch JS. Use of whole-genome sequencing to diagnose a cryptic fusion oncogene. JAMA. 2011Apr20;305(15):1577–84.
  9. NCI Staff. How CRISPR is Changing Cancer Research and Treatment [Internet]. National Cancer Institute. 2020 [cited 2022Jan2]. Available from: https://www.cancer.gov/news-events/cancer-currents-blog/2020/crispr-cancer-research-treatment
  10. Zhang H, Qin C, An C, Zheng X, Wen S, Chen W, et al. Application of the CRISPR/cas9-based gene editing technique in basic research, diagnosis, and therapy of cancer. Molecular Cancer. 2021;20(1).
Categories
CRISPR Genomics Precision Medicine

The State of Gene Therapies

Nima Karimi — McMaster University Health Sciences 2023

As the quest of mankind for optimal health continues,  different avenues for achieving this goal have emerged. One area, in particular, is looking at the role of genes in the pathophysiology of diseases, and consequently, investigating therapeutics that target those genes. Genes are the basic functional unit of heredity (1); in other words, they determine your height, the color of your eye and hair, and many other biological traits. Importantly, alterations of the genes and genome have been consistently linked to many pathological conditions. Cystic fibrosis (CF), sickle-cell anemia, and Huntington’s disease are some of the more prominent examples of genetic disorders (2). As these conditions have led to increased mortality and reduced quality of life, the scientific community has searched for potential therapeutics; one, in particular, being gene therapy.

The first human studies on gene therapy were done in the early 1990s. One such experiment involved the transfer of genes coding for a specific enzyme, to patients with severe combined immunodeficiency, which showed promising results (3). Since then, research into gene therapy has grown considerably. More recently, some studies have used gene therapy to treat CF, a progressive genetic condition that leads to the loss of lung function with no current treatment (4). Interestingly, the use of gene therapy in CF patients have shown to improve lung capacity (3). With CF being one of the most prevalent genetic disorders, the use of gene therapy shows a promising future for the treatment of this condition.

Now you may be wondering to yourself, how is genetic therapy actually done? Generally speaking, gene therapy involves the identification of cell types and DNA sequences that are defective, and then introducing a new DNA sequence containing the functional genes to offset the effects of the disease-causing genetic alterations (5). There are two different approaches to gene therapy (figure 1), and these involve alterations of different types of cells (6). Somatic gene therapy involves the transfer of DNA to different cells in our body that do not produce sperm or eggs. Given that these changes are not in the germline, any DNA alteration cannot be passed on from parents to their children (6). In contrast, germline gene therapy involves the transfer of DNA to cells that produce eggs or sperms, meaning these changes can be inherited (6).

Additionally, various techniques are being used in gene therapy. One such technique is gene augmentation therapy (6). This technique can be used to treat genetic abnormalities  that stem from mutation, where the gene in question does not produce its functional products (6, 7). As shown in figure 2, this therapy adds the DNA containing a functional gene back into the cell that is defective and ultimately, can reverse the abnormality (8). Another technique involves gene inhibition (6). This technique can be used in pathologies in which the overexpression of certain genes is causing the disease. In this approach, the aim is to introduce a new gene that either inhibits the expression of another faulty gene, or interferes with the activity of the product produced by the faulty gene (9), as shown in figure 3.

Overall, it is clear that gene therapy presents a very promising future for the treatment and management of diseases that were once deemed incurable. Today, there are more than 600 genes and cellular therapies that are being researched (10). In the coming years, one could expect the emergence of many genetic therapies for common and rare conditions. This emergence could both provide treatments for patients that lack therapeutics today, and also improve their overall quality of life.

References

1.         Kitcher P. Genes. The British Journal for the Philosophy of Science. 1982;33(4):337-59.

2.         Conrad Stöppler M. Genetic Diseases (Disorder Definition, Types, and Examples): MedicineNet;  [Available from: https://www.medicinenet.com/genetic_disease/article.htm.

3.         Steffin DHM, Hsieh EM, Rouce RH. Gene Therapy: Current Applications and Future Possibilities. Advances in Pediatrics. 2019;66:37-54.

4.         Davis PB. Cystic Fibrosis Since 1938. American Journal of Respiratory and Critical Care Medicine. 2006;173(5):475-82.

5.         Verma IM, Naldini L, Kafri T, Miyoshi H, Takahashi M, Blömer U, et al., editors. Gene Therapy: Promises, Problems and Prospects. Genes and Resistance to Disease; 2000 2000//; Berlin, Heidelberg: Springer Berlin Heidelberg.

6.         What is gene therapy? 2021 [Available from: https://www.yourgenome.org/facts/what-is-gene-therapy.

7.         Frazier S. Embryo Gene Editing: Changing Life As We Know It 2019 [Available from: https://the-gist.org/2019/05/embryo-gene-editing-changing-life-as-we-know-it/.

8.         Nóbrega C, Mendonça L, Matos CA. Gene Therapy Strategies: Gene Augmentation. In: Nóbrega C, Mendonça L, Matos CA, editors. A Handbook of Gene and Cell Therapy. Cham: Springer International Publishing; 2020. p. 117-26.

9.         James W. Towards Gene-Inhibition Therapy: A Review of Progress and Prospects in the Field of Antiviral Antisense Nucleic Acids and Ribozymes. Antiviral Chemistry and Chemotherapy. 1991;2(4):191-214.

10.       Dorholt M. We’re on the Verge of a Breakthrough for Gene Therapies 2021 [Available from: https://www.evernorth.com/articles/the-history-and-future-of-gene-therapy.

Categories
Genomics

Unfolding the Code of Cancers Using the Next Generation Sequencing

Christie Siu—McMaster University Honours Life Sciences 2023

By accessing multiple genes in a single assay to identify causative  mutation, next-generation sequencing provides a more efficient and  deeper look into molecular underpinnings of patients’ tumors. 

Not so long ago, it seemed mapping and understanding the entire human genome  sequence was one of the most expensive and time-consuming studies to accomplish. The  Human Genome Project, initiated in 1990, took a total of 13 years and about $3 billion  USD to determine and study the complete human genome, by using the traditional DNA  sequencing technique—”Sanger sequencing.” Yet, the advent of next-generation  sequencing (NGS) has made a great impact on clinical and molecular biological  research, more specifically—cancer research, leading to the molecular age of cancer. 

Before the 1990s, DNA sequencing was accomplished in an “old fashioned” way by adding agarose gel  and targeted genomic bases manually. Later, the Sanger sequencing technique was introduced into the  biological market and allowed researchers to process long DNA fragments at one time. And the  researching technique evolved, Next-generation sequencing has altered the way that sequencing was  ever performed. Although the invention of the Sanger sequencing did allow researchers to map out the  entire human genome sequence, it is unexpectedly costly and time-consuming for diseases diagnosis  and implantation of treatments of patients, especially individuals that are aware or not aware that, they  themselves are suffering from cancers (1). 

Cancer is one of the most leading cause of death worldwide. According to the National Cancer Institute,  there are related deaths in 2018. In addition the the enormous number of cases that can be studies,  cancers are generically complex and requires high-accuracy targeting specific variants and activation  pathways. Undoubtedly, the success of the Human Genome Project, along with the increased  affordability of sequencing, has implanted the wide use of genomic data to assist in cancer diagnosis and  medicine precision. The development of Next-generation sequencing, once thought to be a novelty,  allows researchers to capture and process a massive amount of genomic information about a cancer in  the shortest time one can imagine- taking only about 4 hours to complete a run (2).

Global Cancer | HEAT: Health Evaluations + applied Therapeutics
SOURCE: GLOBOCAN 2018
Individuals in both the developed and developing countries experience cancers, while most patients  were concentrated in Europe and Asia (3). 

Next-generation Sequencing VS Sanger Sequencing  

In principle, the concepts behind the two DNA sequencing techniques are similar. Both of NGS and  Sanger sequencing requires addition of DNA polymerase to the fluorescent nucleotide according to a  growing DNA template strand, while each nucleotide is identified by their fluorescent tag. But in NGS,  DNA fragments are massively parallel, which allows tones of fragments to be sequencing in just a single  trial. Whereas sanger sequencing sanger sequencing only produces one forward and reverse read of a  single fragment, and in other words, researchers have to be determinant when deciding which DNA  fragment, they are interested in.

When Do I Use Sanger Sequencing vs NGS? - Behind the Bench
SOURCE: Natalie Gurson, ThermoFisher Scientific
The fundamental approach of identifying target DNA sequence in NGS and Sanger sequencing is  similar, but their sequencing volume are different. While only a single DNA fragment can be  sequenced at a time in Sanger sequencing, and alternatively, NGS is massively parallel, millions of  fragments can be translated into genes simultaneously in a single run. 

Compared to the traditional way of sequencing, NGS offers high accuracy, sensitivity, and speed in  genomic investigation (4), as it only requires as little as 5% of the DNA sequences from a tumor sample,  and it can reduce the need to preform multiple tests to examine causative mutation within a patient.

References

1. Vincenza Precone, Valentina Del Monaco, Maria Valeria Esposito, Fatima Domenica Elisa De Palma,  Anna Ruocco, Francesco Salvatore, Valeria D’Argenio. Cracking the Code of Human Diseases Using Next Generation Sequencing: Applications, Challenges, and Perspectives. *BioMed Research International*,  vol. 2015, Article ID 161648, 15 pages, 2015. Available from: https://www.hindawi.com/journals/bmri/2015/161648/.

2. Gurson N. When Do I Use Sanger Sequencing vs NGS? – Behind the Bench [Internet]. Behind the  Bench. 2021 [cited 11 March 2021]. Available from: https://www.thermofisher.com/blog/behindthebench/when-do-i-use-sanger-sequencing-vs-ngs-seq-it out-7/.

3. Bray F, Ferlay J, Soerjomataram I, Siegel RL, Torre LA, Jemal A. Global cancer statistics 2018:  GLOBOCAN estimates of incidence and mortality worldwide for 36 cancers in 185 countries. CA Cancer J  Clin. 2018;68(6):394–424. 

4. NGS vs. Sanger sequencing. (n.d.). Retrieved March 11, 2021, from https://www.illumina.com/science/technology/next-generation-sequencing/ngs-vs-sanger sequencing.html.