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Introduction to Modern Omics

Agus Salim, Ph.D

Big Data Analytics: Application to Modern GeneticsUniversitas Jember, 23 Dec 2015

Agus Salim, Ph.D Introduction to Modern Omics

Background

In 2001, Human Genome Project (HGP) together withCelera comes up with a draft of Human Genome(complete map in 2004)

What is a (Human) Genome?


What is the DNA?

DNA is the basic building block of genes

It is composed of 4 letters (A,C,G,T), wrapped in adouble-helix structure.

The analogy DNA (letter) make Genes (sentences) and acollection of genes make chromosome (chapter).

Human has 23 pairs of chromosomes (22 autosomes, 1sex)


Central Dogma of Genetics

This opened unprecedented opportunities to understandthe mechanisms behind human traits (phenotypes),disease and (hopefully) discover cure for those diseases.

After all, the DNA is the basic code book of genetics.

Central Dogma of Genetics:DNA =⇒ RNA =⇒ Protein =⇒ Phenotype (Trait)


Major types of ’Omics study

Genomics: Comprehensive study of DNA at organismscale

Transcriptomics: Comprehensive study of full set of RNA(transcripts)

Proteomics: Comprehensive study of full set of proteins

Metabolomics: Comprehensive study of full set of smallmolecules (metabolites)

Methyleomics: Comprehensive study of DNA methylation


Common Themes in ’Omics Data

Driven by the latest technology

High-throughput: large volume of data produced inrelatively short time

Low signal-to-noise ratio

Contain a lot of artifacts (bias)

Use of known databases to enhance findings


Technologies Used in Omics study: Microarray

An array can contain upto 20,000 spots. Each spot hasbeen implanted with ’target’ DNA sequence (1 spot ∼ 1gene).DNA from one or two samples are hybridized to the’target’, with each sample dyed with different color.


Technologies in Omics study: Microarray

The amount of hybridization from each sample dependson the amount of sequence that matched the targetsequence

More in sample A (red), More in sample B (green), equalamount (yellow)


Technologies in Omics study: Next-gen sequencing

Microarray technology only allows studying transcripts atgene-level

Next-gen sequencing (NGS) allows us to study transcriptsat sub-gene (e.g., exon) levels.


Technologies in Omics study: Next-gen sequencing

DNA is denatured, chopped randomly into short fragment

The sequencing machine will then scan (’read’) thesequence of letters from each end of fragment.

Unlike microarray data, initial NGS reads do not belongto any transcripts (genes); alignment is needed to mapthe reads back to the genome.

There is also problem since more reads will be mappedback to longer genes, purely due to chance alone.


Technologies in Omics study: LC (GC) - MS

Chromatography is popular for (physically) separatingmolecules; Mass-spectrometry is needed to measure themolecule weight

LC (GC) - MS is popular for proteomics andmetabolomics study

The data is usually in the form of spectra


Databases for Omics studies

Reflect knowledge accumulation over time

Refinement of gene boundaries; novel exons; howprotein-protein interacts; how DNA-protein interact.

Some examples:

Refseq (http://www.ncbi.nlm.nih.gov/refseq/):contain (experimentally-validated) reference sequences,transcripts and proteinsBioGRID (http://thebiogrid.org/: databases ofinteractions (mostly protein-protein and DNA-protein)KEGG (http://www.genome.jp/kegg/: pathway andinteraction databasesGEO (http://www.ncbi.nlm.nih.gov/geo/):publicly-available high-throughput datasets


http://www.ncbi.nlm.nih.gov/refseq/

http://thebiogrid.org/

http://www.genome.jp/kegg/

http://www.ncbi.nlm.nih.gov/geo/

Some Useful References

Ridley M. (1999). Genome: The Autobiography of aSpecies in 23 Chapters

Ridley M. (2003). Nature via Nurture: Genes, Experience,& What Makes Us Human

Ryan F. (2015). The Mysterious World of the HumanGenome.


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