06/09/2022 / Medical Advances
Genomic Technologies: Your personal guide to genomic education
Genomic technologies analyze data of human genome and genes to unmask the in-depth mystery and details of complex biological diseases to get new insights.
Introduction
Types of mutation in genetics, A basic in introduction to genomic technologies
Single cell genomics-Introduction to new age of human genome technology
Introduction to Genomic technologies in tumor DNA sequencing and analyses
What are Copy Number Variations and their importance in genomic technologies
Microbial single cell sequencing-Another innovation in genomics technology
Single cell transcriptomics- A future introduction to genomic technologies
A Basic Introduction to Genomic Technologies
Do you know what genomic technologies are?
Genomic technologies manipulate and analyze the genomic information. With introduction to genomic technologies, the scientist are studying DNA and gathering clues to mystery and biology of complex diseases.
The important areas of genomic technologies includes high throughput genome sequencing, CRISPR and single cell genomics.
What is a genome?
A genome is a set of nucleic acid coded as DNA within 23 chromosome pairs. It has all the information of the body. The genome is stored in chromosomes which are long molecules of DNA.
What is a gene?
The basic unit of inheritance is called a gene which is passed on to the offspring from the parent. Genes contains all the information that represents the physical and biological trait of an individual. Human have 20,000 protein coding genes. Genes are small sections of DNA.
All the cells and tissues in our body are made of proteins and these genes are the part of our genome that codes information to make those proteins. Due to introduction to genomic technologies, it is possible to study genetic make up of an individual and predict quality of unknown disease status.
What are genomic technologies?
The genomics technology is an advanced technology which is personalized. Human genome technology manipulates and analyze genomic information that solves biggest human problems when it comes to a genetic disease.
These genomic technologies can help in all dimensions of disease like:
Understanding
Diagnosis
Prevention
Treatment
Prognosis
Mutation in human genome technology
When there is a change in the sequence of DNA, we call it a mutation. They occur when cells divide and replicate.
Sometimes changes in the DNA do not create health problems, but sometimes some DNA mutations produce genetic conditions which adversely affect health. Genomic technology detect these changes.
Types of mutation in genetics, A basic in introduction to genomic technologies
There are two types of mutation:
Germline
Somatic
Germline mutations occur in parent’s reproductive cells like egg and sperms. This changes genetic composition in such a way that same is transferred from parent to the child and causes hereditary diseases.
Somatic mutations have no relation to egg and sperm. This DNA change occurs after conception and is not hereditary. It has no connection with family history nor it can be passed on to the future generation.
Why these mutations are challenging?
The somatic mutation occurs randomly. A cell formed from a mutated cell will contain mutated DNA. In this way, several copies of mutated cells are formed.
These genomic technologies identify the mutations at all levels like gene, chromosomes and proteins. Genomic technologies by genetic testing can warn the parents of having a child with a genetic condition associated with a positive medical history.
With the introduction of genomic technologies, continual advancement and software development, this genetic journey is been continuously loaded with quality research information and is improving life of many diseased individuals.
Diseases of mutation-Naming few with a point
Medical conditions of germline mutation:
Lobular breast cancer
Gastric cancer
Myelodysplastic syndrome/Acute leukemia
Syndromes associated with somatic mutation:
McCune Albright
Maffucci syndrome, a type of severe overgrowth syndrome
Creutzfeld-Jakob disease
It would be a very broad aspect to say that somatic mutations are related to neurological diseases.
CRISPR-The real power of genomics technology
CRISP stands for Clustered Regularly Interspaced Short Palindromic Repeats.
This genomics technology tool enables researcher to study the main biology behind the mutation. The scientists can correct mutations in the genome with a high level of precision with easy usage.
At first, CRISPR was studied in the mouse and human cells. But today its application has spread a lot to biological systems and disease areas. It has grabbed researcher attention and has opened new door of research in human genome technology.
System of CRISPR: The main backbone of genomics technology
This genomics technology is the most revolutionary in the field of genetic editing. This has given the power to change the DNA of the organism so that the genetic material can be added, subtracted or altered.
CRISPR Cas-9 system is adapted from natural immune defense of bacteria. It is the genomics technology which bacteria uses.
When a bacteria is infected with the virus, bacteria captures a small portion of viral DNA and insert it into its own DNA to remember the virus. This are known as CRISPR arrays. When the bacteria gets attacked by the virus again, CRISPR arrays produce RNA segments that attach to specific regions of viral DNA. Then Cas 9 enzyme is used by the bacterium to cut the DNA and disable the virus. Can you think how advanced bacterial genomics technology is?
This same concept is used in editing DNA in human genome technology. Cas9 cuts down the DNA and researchers use cells own DNA repairing machinery for the useful corrections.
Cpf1 enzyme can also be used. A lot of research is going on to determine the safety and effectiveness of CRISPR in human.
Applications of CRISPR in human genome technology
It is being researched in single gene disorders and complex diseases like:
Cystic fibrosis
Sickel cell anemia
Hemophilia
Cancer
Heart disease
HIV
Mental illness
A SMALL CRISPR MACHINERY
CRISPR needs two operables:
Enzyme like Cas9
A Programmable system
Single cell genomics-Introduction to new age of human genome technology
In this genomics technology, A single cell is studied like RNA, DNA and proteins to establish link between genotype and phenotype.
We always read and write about DNA but RNA also has something interesting. RNA is loaded with tonnes of information related to phenotype.
Indications and research applications of single cell genomics
The single cell genomics is very useful in following field of medicine:
Oncology: study of cancer
Prenatal diagnosis
Tissue mosaicism
Immunology
Organ formation or organogenesis
Embryogenesis
Neurobiology
Microbiology
Research applications includes:
Pathogenesis of disease initiation
Disease progression
Applicability of single cell genomics technology in treatment :
Predict response to treatment
Discover novel biomarkers
Prognosis
Residual disease after initial treatment
A TO Z About single cell genomics technology
Principle: To determine and link in genomics technology
The first step is to determine cellular heterogeneity. This means to detect the behavior of cells by observing either small groups of cells over longer time of time or by studying large number of cells in smaller time. This is the main step which establish molecular mechanism of disease.
The second step is to link cell heterogeneity with disease phenotype using computational analysis.
Statistical and computational method extract meaningful information from data which makes population level studies possible.
The Actual Concept Of Single Cell Genomics Technology:
Individual cell state is disturbed in a disease. These disturbances together produce changes at tissue level. When we take a drug or eat a diet, molecular changes are produced in cells to fix the aberrancy. Further changes are produced at higher level physiology to improve health status. This can be done with genetics and introduction to genomic technologies.
For example, like in atherosclerosis, cell types involved are fibrochondrocytes, macrophages, smooth muscle cells and lymphocytes. These cells form atheroscleromatic plaque. The goal of treatment here is to promote stability of the plaque. A model can be created to study how these cell types interact and relate to the stability of the plaque. No such model exists yet but there is a future hope that such a model would be prepared using single cell genomics technology.
Advantages of single cell genomics technology
To prepare model and see how cells interact and produce tissue level physiological alterations.
To study how cells interact with each other and with the distant cells. For example: Serum glucose level is regulated by cells of liver, pancreas and skeletal muscle.
Is there any limitation of single cell genomics technology?
Yes,there are limitations. They are
Cost
Tissue handling
Introduction to Genomic technologies in tumor DNA sequencing and analyses
The introduction of genomic technologies have led to the identification of possible mutations in a patients tumor. This is possible with high throughput tumor samples sequencing. This gives an accurate diagnosis on the basis of which most appropriate and selected therapy can be chosen. This selective therapy is the biggest advantage of genomics technology.
ISOWN software in human genome technology
The biggest challenge in diagnosing somatic mutations comes from its comparison with the normal tissue. Sometimes normal tissue is not available for comparison due to patient consent, retrospective studies, etc.
To overcome this challenge ISOWN software was introduced by Lincoln Stein. ISOWN stands for Identification of Somatic mutations Without matching Normal tissues.
This software collaborates with machine learning and external database to accurately diagnose somatic mutations.
What are Copy Number Variations and their importance in genomic technologies
Copy number Variations (CNV) identify the regions of the genome involved in the disease phenotype. This includes copy number, gene content, frequency, etc. They are risk factor in cancer. Gene amplification means copy number gain. Gene deletion means copy number loss.
It is important to diagnose these copy number variations as they are related to:
Growth of the cancer cell.
Cancer progression
Drug sensitivity
Drug resistance
Treatment plan
Repeat HMM software in human genome technology
Identification of genomic rearrangement is very challenging. It has two aspects:
Short read sequencing
Long read sequencing
Short read sequencing
It read DNA alterations of chromosomes and has suboptimal accuracy. But this reading is till 600 bases. This is expensive and labor intensive.
Examples includes
Illumina’s NovaSeq
HiSeq
NextSeq
Thermo Fisher’s Ion Torrent sequencers
A challenge with solution in human genome technology
Huntington’s disease can be identified only after reaching a threshold trinucleotide count and the disease severity is identified by the number of repeats.
Short read sequencing is only upto 600 bases, so do we not have this question in our mind that if a genetic disease does not fall in this range of counting then is it possible to identify it? This is overcome with long term sequencing in introduction to genomic technologies.
Long read sequencing: This can read up to excess of 10 kb with high level of accuracy, throughput and reduced cost.
Principles of long read sequencing in introduction to genomic technologies:
There are principles of long read sequencing
Structural variant calling. Conversion from raw data to nucleic acid sequence.
Error correction
Detection of base modifications
Transcriptomics
Procedure of long read sequencing
Steps in long read sequencing:
Assembly
Mapping
Identification of transcript isoform
Detection of structural variants.
Two dominating long read sequence includes:
Pacific Biosciences Single Molecule Real Time Sequencing.
Oxford Nanopore Technologies(ONT) or nanopore sequencing
Nanopore sequencers provide longest read length from 500 bp to 2.3 Mb with 10-30 Kb genomic library. They are quality oriented and does not depend upon the length of DNA.
Examples of nanopore sequencers are:
MinION
GridION
PromethION
svmSomatic in introduction to genomic technologies
This is the machine learning approach which performs the following in genetic testing:
Distinguish between germline and somatic mutations by a support vector machine algorithm.
Detects CNV with Next-Generation Sequencing (NGS) data from individual tumor samples.
Merging of long term sequencing (third generation sequencing ) with the bioinformatic tools is the greatest innovation in human genome technologies.
Repeat HMM Scan
This software and its application in Short Tandem Repeats (STR )are represented by Wang et al and Liu et al based on long read sequence performance.
These Short Tandem Repeats are abundant in human genome and are associated with diseases when count is abnormal. This is because they have a specific repeat expansion in diseases.
This Repeat HMM scan determines the normal repeat and pathologic repeats in this sequence. A whole scan of human genome is performed to identify disease. One such example is spinocerebellar Ataxia Type 3 diagnosed by Liu et al with 5 undiagnosed cases.
This scan determines the present and undiagnosed disease status.
Brain-coX in introduction to genomic technologies
Neuropsychiatric genomics is evolving.
Introduction of genomic technologies has made our understanding of mendelian diseases easy and treatment approachable.
When we identify a gene involved in the complex genetic disease, the whole outlook of understanding, diagnosis and treatment changes. To be specific, it becomes more precise and accurate.
Brain-coX as web application introduction to genomic technologies:
Melanie Bahlo has created a web application called brain-coX which gives priority to those genes and gene networks involved in neurological disorders. This made mapping of psychiatric diseases easy.
Microbial single cell sequencing-Another innovation in genomics technology
There is a link between microbiome and cancer. The example being colorectal cancer and high level of Fusobacterium nucleatum.
Ramnik Xavier and Andrew Tolonen discussed state-of-the-art-microbial single-cell-sequencing technology and highlighted how we can identify microbiome at cellular level and find out its role in immunity and disease.
These studies have wide applications in human diseases.
Disease pathogenesis.
The state of cell associated with the disease status.
Generate hypothesis.
To obtain tissue level information like stability of atherosclerotic plaque.
Improvement of tissue level measures
Data introduction to genomics technologies
The National Center for Biotechnology Information is developing database which can be used by the research community.
In NCBI dbGaP database, the genomic studies related to age related eye diseases and neurological diseases like Parkinson disease are available.
Due to the low cost of sequencing , many countries are adopting such data driven treatment in clinical research and healthcare. Many people are benefited out of this therapy.
Genome wide association studies
This technique detects genetic diseases with the help of disease markers. This is a study in which an entire set of DNA is scanned for markers in many people to find out if a disease is associated with genetic variation.
When this genetic variation is detected, research is done. This information is used by researchers to develop better strategies to diagnose, prevent and treat the disease. The genetic variations are related to many conditions like asthma, cancer, diabetes, mental illness and heart disease.
Importance of studies in human genome technology
Personalized medicine
People will be informed of their health and risk of developing diseases.
Selective treatment
Reduced adverse effects associated with the treatment.
Study conduction in human genome technologye
Researchers use two groups of participants. One with disease and the other group in which people do not have any disease.
DNA sample is obtained from blood or cotton swabbing from mouth to harvest the cells. The DNA is then purified and placed on chip for scanning on automated laboratory machines.
These laboratory machine scans selective markers of genetic variations called single nucleotide polymorphism.
Commercially available SNP chips
Affymetrix SNP Array 5.0
SNP Array 6.0
Illumina HumanHap300
HumanHap550
HumanHap650Y
Human1M
OmniExpress Chip
Two methods from Affymetrix and Illumina i.e, the Affymetrix GeneChip and Illumina BeadChip have provided 95 % accuracy in genotype.
Red-A new detective introduction to genomic technologies
Red stands for REpeat Detector.This is machine learning based genomic tool. Red is the first repeat detection tool which can label its data and train itself automatically on entire genome. It is much faster and has a low false positive results.
The most unique aspect of Red is it can process genome which has unusual nucleotide composition, bacterial genomes and unassembled genomes.
It is sensitive to both Transposable element (TE) and Tandem Repeats (TR).
Red is Fast and detect genome of:
Mycobacterium tuberculosis
Drosophila Melanogaster
Plasmodium falciparum
Dictyostelium discoideum
Zea Mays
Glycine Max
Few limitations of the software include library preparation, error and cost.
Other tools of human genome technology are
The other tools of genomics include:
RepeatScout
Recon
TumorNext
UNMASC
Proteogenomics in human genome technology-The future
This human genome technology identifies drug targets in cancer. This is the most important determining factor in therapeutic outcomes in a precise way.The database selection is important to get precision results in proteogenomics.
With introduction to genomic technologies like proteogenomics, those germline and somatic mutations can be identified which might have got missed during gene identification in genomics and transcriptomics. This potentially impacts cancer biology.
Single cell transcriptomics- A future introduction to genomic technologies
This future technique is so powerful that it can map all cells, tissue and organs at single-cell resolution. This is the atlas of human cell.
Genomics technology devise better therapy.
A meaningful interpretation
Molecular and genetic testing is gaining widespread research to improve the quality of human health and body. In future, Early Diagnosis For The Early Treatment is possible with genomics study.
Take-home points
Genomic technologies are expanding at a much faster rate. You must have heard or read from somewhere that science and technology is traveling more than the speed of light. You can imagine how fast we are moving towards a future where treatment of every complicated disease is possible. One of the biggest contributors to this success is Genomics.
You can keep yourself updated on Genomics by searching through various database available.
FAQ on genomics technology
Genomics is the study of complete set of DNA.
There are 4 branches, structural, functional, comparative and mutational.
Genome was introduced by Hans Winkler in 1920. He was a botanist.
Breast and ovarian cancer, colorectal cancer, cystic fibrosis, diabetes, heart disease, obesity, osteoporosis, etc.
Family history, diet, physical activity and environment.
Comments ( 0 )
No Comments
Leave a Comment
Health & Wellness Tips
Subscribe to our blog