Introduction to genomics, proteomics, transcriptomics,

metabolomics 
 NGS: Next-generation sequence 
 This technology hep to determine the order of the nucleotides and the targeted
region of DNA or RNA
 They can also find the origins of the mutations and potential variants that can
create cancer or some diseases. They can detect the genetic variants such as
the single nucleotide variants (insertions/deletion) 
 They can apply to any species such as livestock, plants, or microorganisms 
 The application of the Next Generation Sequence is 
 Rapidly sequence the whole genome
 Deeply sequence the targeted regions 
 Use the sequence of RNA to find the RNA variants and quantify the
number of mRNAs when the gene expressions
 Sequence the cancer cell to study some variants, tumor subclones
(các biến thể soma), and more 
 Identify the novel pathogens  
 The process of the next-generation sequence 
 Fragmentation: Make DNA become smaller (fragments)
 Ligation with certain oligonucleotides (2 types) 
 Binding to the chips: Each fragment has different chips to bind 
 DNA amplification: With the polymerase chain reaction they will form the
complementary sequence 
 Wash away: The single strand will wash away and then we still have one strand 
 Bridging building: The strands will make a bridge with another chip (suit with
the certain types of oligonucleotides) 
 Amplification again: From the bridge, they will form the another strand 
 Bridge amplification: They will create 2 DNA strands riêng biệt 
 Bridge-building again and repeated 
 Sequencing: They will use the laser light to label the color of nucleotides 
 Compare with the reference genome: To find the differentiation 
 The exome sequence: 
 They represent less than 2% of people's genome but they contain many known
diseases that can cause the variants. So that they can be used instead of using
the NGS to reduce the cost 
 In this technique, phần mã hóa đã được mã hóa protein sẽ được đem đi giải
trình tự gen và phát hiện ra các biến thể từ đó có thể dùng các phương pháp
điều trị 
 Shot-gun sequences
 Illuminate 
-> Combine the technique NGS and Illuminate. Then we analyze the blast 

 In the proteomic, we explore MS (mass spectrum), peptide sequence, 3D structure

(NMR - nuclear magnetic resonate: cộng hưởng từ hạt nhân), X-ray crystallization,
interaction (ligand-protein) 
 The ligand-protein:
  When the body undergoes the metabolism process -> human body needs
oxygen. But the oxygen is nonpolar so it cannot soluble in the bloodstream ->
need the help from the protein (hemoglobin) 
 The protein (hemoglobin) will carry the oxygen from the lung and dumps the
oxygen into the tissues 
 The hemoglobin is the tetramer (have 4 subunits - 2 alpha and 2 betas). They are
positive cooperatively.
 There are 2 example models of the ligand-protein interaction: 
 About the sequential models: We have a T state (lack of oxygen) and an
R state (rich in oxygen). During the process of oxygen-binding into the
subunits, there are an intermediate exists between the T state and R
state -> Greater affinity of subunits and helps the second oxygen bind into
the subunits easier than the initial 
 About the concreate models: The T state and R state exist in the
equilibrium condition. Each step also contains the R state -> Increase the
greater availability 
 Note that: Many types of enzymes are controlled by the ligand-protein so
that when the ligand-protein interaction happens -> They will turn on the
enzymes -> Can determine the enzymes in the human body 
 Based on the interaction of ligand-protein -> Can see the enzyme of humans.
 How can the enzyme bind to the drugs and how does the toxin? 
Genomics: About the profile of the genome 
 About cancer: Try to find the mutation 
 Person 1: How SNP1 mutation 
 Person 2: How SNP2 mutation 
-> Then analyze how people's percentages have SNP1 and SNP2. Then we
compare it with the normal people -> We cannot conclude the risk of cancer. It is
very difficult to diagnose the cancer 
-> The proteomic tells you which expressed protein/regulator (up and down, turn
on and turn off). 
-> Base on the genomics we cannot conclude that cancer 

 Whole-genome sequence: 1 organism -> isolate the genomic DNA (Explore) -> Use
the NGS/Illuminate -> Read -> Whole-genome sequencing -> Analyze the nucleotide
sequence -> Use blast -> Information of the gene 
 Note:Predict: Antibiotic resistance, virulence factor, and transporter (in silico - no
100% accuracy) 
 Tìm hiểu kháng sinh quinolone, chloramphenicol, cephalosporin
 Antibiotic quinolone:
 The origin of these antibiotic quinolone groups is not from nature. They are from
the chemistry synthesize
 The function of these antibiotic quinolone groups is is destroying the bacteria.
The help DNA can open its spiral to help the DNA do the transcription and
translation. They also affect the mRNA  -> affect the synthesis of protein 
 The quinolone in the first generation will have a narrow effect on the number of
bacteria. They do not have effects on the Pseudomonas bacteria. But when the
structure of quinolone can attach to the flour in position 6 -> They will have side
effects and the ability to destroy the bacteria will increase from 1-to 30 times  
 In silico (predict) -> Determine the quinolone but then experiment the result is sensitive
to quinolone 
  Lquan gì tới nghề của mình và application  
Proteomics - Protein profile: 
- The method 2D (2-dimension) SDS (sodium dodecyl sulfate-polyacrylamide)-PAGE
electrophoresis 
- Person with cancer: Having a strange protein may involve cancer development. Isolate the
strange protein. Then we measure the protein sequencing -> ra được những chuỗi sau đó dùng
các technique để check các sequence đó -> Phát hiện cancer 
- Sự khác biệt giữa máu người và máu gà và động vật khác 
- Apply in the basic and mechanical research 
- We have methods: Isolation 
- 
Metabolomics:
 Transplantation: Introduce organs/tissues/cell mass in the human. Then start to see the
people just think the phenotype observed -> Need metabolism to explain 
 Person 1 wants to be successful: products (how the enzymes, cytochrome, and
transcript 
 Person 2 fail? Because they do not see any products produced. They use the methods:
Liquid chromatography-mass spectrum -> Can determine which products are produced 
 MinD: appear in microorganisms and humans, and they contain the most living
organism 
 MinC and MinE just appear as microorganisms 
 Why does the microorganism produce anticancer drugs and antimicrobial agents?
 Taxol (terpenoid/taxus wallichiana - cây thông đỏ) and vincristine (from
fungi/catharanthus roseus - cây dừa cạn) -> anticancer 
 Peniciling, ampicilin, bacitracin
-> They are metabolites - make many different things in microorganisms and involve in
gene expression 

 Explore the blast, fasta, gene bank, protein, and data bank 
 Relationship between the metabolism and cancer (metabolite) 
Obesity: 
 Person 1:  
 Person 2:
 In the body, we have gluconic tolerance -> diabetic type 2 cannot develop  

1. Molecular cloning (nhân dòng): Amplify the gene and Store the gene 
2. Molecular diagnosis 
3. Gene expression 
4. Pathway