1. Bioinformatics: Data-driven molecular biology
Mikhail Gelfand
A.A.Kharkevich Institute for Information Transmission Problems, RAS
Moscow
II Испано-российский форум по информационным и коммуникационным технологиям
Madrid, / IX / 2009

2. Exponential increase of data volume
red – papers (PubMed)
blue – sequence fragments (GenBank)
green – nucleorides (GenBank)
of 18 million papers in PubMed, ~675 thousand have keywords “bioinformat* OR comput*”

3. 622 complete genomes (bacteria)

4. >45 thousand Google hits on “genome deciphered”
Top 10 hits:
bioremediation
bacterium Pseudomonas
agriculture and biotech
crop and biofuel plant Sorghum
rice
medicine
pathogenic bacterium Staphylococcus
SARS (atypical pneumonia) virus
Brugia worm (elephantiasis)
individual genome (medicine)
James Watson
science / model organism
macaque
science / evolution
mammoth (mitochondrial)
platypus

5. Sequencing is just the beginning
Bacterial genome: several million nucleotides
600 through 9,000 genes (~ 90% of a genome codes for proteins)
This slide: 0,1% of the Escherichia coli genome
Human genome: 3 billion nucleotides, thousand genes
polymorphisms (individual differences): ~ 1 for 1000 nucleotides
differences between human and chimpanzee: ~ 1 of 100

6. Not just genomes Other types of large-scale experiments / datasets:
State of the genome (gene expression)
methylation
nucleosome positioning
histone modifications
Transcriptomics, protein abundance (gene expression)
Protein-protein interactions
signaling etc.
functional complexes
Protein-DNA interactions (regulation)
etc. etc.

7. Goals Functional annotation of genes and proteins
biological function
regulation (in what conditions)
Functional annotation of genomes
metabolic reconstruction and modeling
regulatory networks and development
prediction of organism properties from its genome

8. Applications: biotechnology
Improvement of production strains (chemistry, pharma, food industry)
via modeling of metabolic pathways
New enzymes (new functions, stress tolerance)
via sequencing and functional annotation
Biofuels
fast-growing, stress-tolerant plants; identification of genes
microbes as producers of ethanol or fatty acids: targeted genome design

9. Applications: medicine and pharma
Personalized medicine
identification of predisposing alleles: lifestyle
pharmacogenomics (metabolic alleles)
diagnostics
Drug targets (chronic disease)
analysis of signaling pathways
Anti-infectives
identification of drug targets
Drug design; identification of drug candidates
modeling of protein structure and interactions of proteins with small molecules

10. Methods. Integration of data
Systems biology: Integration of diverse datasets for one organism
Comparative genomics: Simultaneous analysis of genomic data for many organisms
Comparative systems biology: understanding the evolution of gene regulation and expression, signaling etc.
Comparative structural biology

11. Bioinformatics in Russia
Few high-throughput experiments
Open data
Collaborations
Theory (evolution), methods, algorithms
Highlights:
Evolution (IITP RAS) and taxonomy (IPCB MSU)
Regulation (FBB MSU, GosNIIGenetika, IITP RAS, ICaG SB RAS)
Annotation (FBB MSU, IITP RAS)
Protein Structure (IPR RAS, IMB RAS, IPCB MSU, BF MSU)
Modeling
Metabolism (IPCB MSU, ICaG SB RAS)
Regulation (SpBSPU , ICaG SB RAS)
Drug design (IBMC RAMS)

12. Research and Training Center “Bioinformatics”, Institute of Information Transmission Problems (5 years: )
Molecular evolution
Alternative splicing as a driver of evolution in eukaryotes
Positive selection
Comparative genomics of regulation in bacteria
Evolution of regulatory pathways
Protein-DNA interactions
Annotation
Gene recognition
Functional annotation
Regulation

13. Comparative genomics in action: confirmed predictions
Regulatory mechanisms
riboswitches (riboflavin – vitamin B1, thiamin – vitamin B2)
antisense regulation of the methionine-cysteine pathway
role of the ribosome in zinc homeostasis
Regulators: NrdR, MtaR/MetR, CmbR, NiaR
Enzymes: FadE, ThiN, TenA, CobZ, CobX/CbiZ, PduX, NagP, NagB-II
Microcins (capistruin, Burkholderia thailandensis)
Transporters
АВС-transporters with universal energizing components: Co, Ni, biotin (vitamin H), thiamin (vitamin B2), riboflavin (vitamin B1)
other: threonin, methionin, oligogalacturonides, N-acetylglucosamin, corrinoids, nyacin, riboflacin, Co
Regulatory motifs: nitrogen-fixation, fatty acid biosynthesis, iron homeostasis, catabolism of chitin and pectin
Regulatory sites: several dozens

14. Functional annotation of genomes
First Russian bacterial genome, Acholeplasma laidlawii (2008): sequencing and proteomics: Institute of Physico-Chemical Medicine;
annotation: IITP: ~1,5 Mb; ~1400 genes. Established function for ~80% genes; metabolic reconstruction

15. Publications (refereed)

16. Collaborations European Laboratory of Molecular Biology * Germany
Humboldt University, Berlin
Munich Technical University
France
Lyon University
United Kingdom
University of East Anglia
Spain
Center for Genome Regulation (Barcelona)
USA
MIT
Burnham Institute *
Lawrence Berkeley National Laboratory *
Stowers Institute *
Rutgers University
China
China-Germany Partner Institute of Molecular Genetics (Shanghai)
Industry
Biomax (Germany)
Interated Genomics (USA)
Bold: on-going
* Former students