PPT - Molecular Modelling & Bioinformatics Group

Bioinformatics
Structural and functional prediction Master in Molecular
Biotecnology 2010-11
Ramon Goni
rgoni@mmb.pcb.ub.es

• Introduction
• Biological Databases
• Sequence Comparison
• 3D Structure visualization
• Functional Prediction
• Structural Prediction
Outline
http://mmb.pcb.ub.es/MBIOTEC/

Material and Evaluation
• Exercises and slides
– Campus Virtual
– http://mmb.pcb.ub.es/MBIOTEC
• Evaluation.
– Practical test on Campus Virtual.

Bioinformatics: Overview

• Bioinformatics or computational biology is the use of
techniques from applied mathematics, informatics, statistics, and
computer science to solve biological problems.
• A common thread in projects in bioinformatics and computational
biology is the use of mathematical tools to extract useful
information from noisy data produced by high-throughput
biological techniques. (The field of data mining overlaps with
computational biology in this regard.)
• Major research efforts in the field include sequence alignment,
gene finding, genome assembly, protein structure alignment,
protein structure prediction, prediction of gene expression and
protein-protein interactions, and the modeling of evolution.
• The terms bioinformatics and computational biology are often
used interchangeably, although the latter typically focuses on
algorithm development and specific computational methods.

• Bioinformatics: Research, development, or application of
computational tools and approaches for expanding the use
of biological, medical, behavioral or health data, including
those to acquire store, organize, archive, analyze, or
visualize such data.
• Computational Biology: The development and application
of data-analytical and theoretical methods, mathematical
modeling and computational simulation techniques to the
study of biological behavioral, and social systems

The Human Genome Project

Tools for Bioinformatics
Genome
sequencing
• DNA Sequence
Biostatistics
Genomic
data
• Gene & Genome
Organization
Protein
structure
prediction
• Molecular Evolution
analysis
Protein
docking
• RNA/Protein
Structure, Function
& Interaction
Molecular
dynamics
Virtual
screening
• Metabolic Pathways
MicroArrays
• Regulation,
Signaling &
Networks

Bioinformatics
Computer Tools
Models
Experimental
Work
Biology
Bioinformatics
Work
Computer
Science
Knowledge
Databases

• Growth of Data
makes unviable to
work manually
with it
• Automated
methods require a
previous step to
store information
• Working with
automated tools
increase the
amount of data
Benefits of Biological Databases

Growth of the
Databases
Data
Information
Information
Data

Bioinformatics Tools

Bioinformatics Tools
Linux
Perl

Sequence Alignment
tcctctgcctctgccatcat---caaccccaaagt
|||| ||| ||||| ||||| ||||||||||||
tcctgtgcatctgcaatcatgggcaaccccaaagt
Hidden Markov Model
Dynamic Programming

Blosum Matrix
Protein Sequence Alignent

Multiple Alignment
ClustalW http://www.ebi.ac.uk/clustalw/

BLAST

GenScan
http://genes.mit.edu/GENSCAN.html

GenScan

http://meme.sdsc.edu/meme/website/meme.html

Protein Structure Prediction

Ab Initio
>MyProtein
MAVTQTAQACDLVIFGAKGDLARRKLLPSLYQLEKAGQLNPDTRIIGVGRADWDKAA
YTKVVREALETFMKETIDEGLWDTLSARLDFCNLDVNDTAAFSRLGAMLDQKNRITI
NYFAMPPSTFGAICKGLGEAKLNAKPARVVMEKPLGTSLATSQEINDQVGEYFEECQ
VYRIDHYLGKETVLNLLALRFANSLFVNNWDNRTIDHVEITV

Homology Modeling
>MyProtein
MAVTQTAQACDLVIFGAKGDLARRKLLPSLYQLEKAGQLNPDTRIIGVGRADWD
KAAYTKVVREALETFMKETIDEGLWDTLSARLDFCNLDVNDTAAFSRLGAMLDQ
KNRITINYFAMPPSTFGAICKGLGEAKLNAKPARVVMEKPLGTSLATSQEINDQ
VGEYFEECQVYRIDHYLGKETVLNLLALRFANSLFVNNWDNRTIDHVEITV

Threading / Fold Recognition
>MyProtein
MAVTQTAQACDLVIFGAKGDLARRKLLPSLYQLEKAGQLNPDTRIIGVGRADWD
KAAYTKVVREALETFMKETIDEGLWDTLSARLDFCNLDVNDTAAFSRLGAMLDQ
KNRITINYFAMPPSTFGAICKGLGEAKLNAKPARVVMEKPLGTSLATSQEINDQ
VGEYFEECQVYRIDHYLGKETVLNLLALRFANSLFVNNWDNRTIDHVEITV

Structure Alignment
http://www.ebi.ac.uk/dali/index.html

RNA Secondary Structure

Vienna RNA Package
RNAFold
Michael Zuker's
RNAstructure

DNA Structure
• NewHelix, Freehelix (Dickerson)
• 3-DNA (Olson)
• Curves (Lavery)

Protein function: Protein Docking

Molecular Dynamics

Bioinformatics Databases

Access to Databases
Application
Programming
Interfaces
(APIs) are an
exclusive
machineoriented
tool
for high
throughput
jobs. Are
rarely provided
by Databases
S
Q
L
Access to databases
using web-interface
is user oriented.
Allow to be rapidly
familiar with the
environment and is
recommended for
sporadic and
specific jobs
Not all the Bioinformatics
Databases provide this service.
SQL is an universal, and very
popular user-oriented and
machine-oriented interface. May
be used for any kind of job

FTP accession

FlatFiles

Databases
Conflicts
Gene
Prediction
NCBI/
EnsEMBL
SEQUENCE
mRNA
Mass
Spectrometry
NCBI/
EnsEMBL
SWISSPROT
ALINEAMENT
Crystal
Diffraction
PDB

DNA Databases

Major Public Databases
European Molecular Biology Laboratory (EMBL)
European Bioinformatics Institute (EBI)
http://www.embl.org
Dna DataBase of
Japan (DDBJ)
http://www.ddbj.nig.ac.jp/
National Center for Biotechnology
Information (NCBI)
http://www.ncbi.nlm.nih.gov/

Accessing genome sequence data
ENSEMBL (EMB + Sanger Institute)
http://www.ensembl.org/
GenBank (NCBI)
http://www.ncbi.nlm.nih.gov/
The UCSC Genome Browser
(University California Santa Cruz)
http://genome.ucsc.edu

UCSC Genome Browser

NCBI

We look forward to working with you all in the future to continue this
tradition as the database continues to grow exponentially

Genome Browser
Show Annotations
Assembly
(Genes, Conserved Regions,
CpG Islands,…)

OMIM

PubMed http://www.pubmed.com

ENSEMBL

• Browsing & Entry Retrieval
• Literature Databases
• Microarray Databases
• Nucleotide Databases
• Protein Databases
• Proteomic Databases
• Structure Databases
http://www.ebi.ac.uk

http://www.sanger.ac.uk/

TRANSFAC
http://www.gene-regulation.com/pub/databases.html

Protein Databases

http://www.isb-sib.ch/
http://www.expasy.org

Swiss-Prot
TrEMBL

http://www.ebi.uniprot.org/index.shtml

Protein Data Base http://www.pdb.org

PDB entry

http://www.expasy.org/prosite/

Protein families database
of alignments and HMMs
http://www.sanger.ac.uk/Software/Pfam/index.shtml

http://www.ebi.ac.uk/interpro/

http://www.cathdb.info/latest/index.htm
l

Gene Ontology http://www.geneontology.org/

Databases
Nucleotide Sequence Databases
RNA sequence databases
Protein sequence databases
Structure Databases
Genomics Databases (non-vertebrate)
Metabolic and Signaling Pathways
Human and other Vertebrate Genomes
Human Genes and Diseases
Microarray Data and other Gene Expression Databases
Proteomics Resources
Other Molecular Biology Databases
Organelle databases
Plant databases
Immunological databases
http://nar.oxfordjournals.org/content/vol33/suppl_1/index.dtl

State-of-the-art in Bioinformatics
Nature Biotech:
• http://www.nature.com/nbt/index.html
Bioinformatics:
• http://bioinformatics.oxfordjournals.org/
Nucleic Acids Research:
• http://nar.oxfordjournals.org/
Journal of Molecular Biology:
• http://www.academicpress.com/jmb
Plos Computational Biology:
• http://compbiol.plosjournals.org/
BMC Bioinformatics:
• http://www.biomedcentral.com/bmcbioinformatics

Institut Nacional de Bioinformàtica
http://www.inab.org/

INB Map

http://genome.imim.es/software/geneid/geneid.html

http://bioinfo.ochoa.fib.es/

INB: BioMOBY

INB:Taberna http://http://taverna.sourceforge.net/