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The document provides an introduction to key concepts in bioinformatics including the central dogma of biology, genes, gene expression, high-throughput biological data, protein structure, protein folding, sequence analysis, gene finding, expression data analysis, definitions of life and evolution, and orthology and paralogy. It emphasizes that computational analysis and data mining are essential to effectively utilize the large and growing amounts of biological data being generated.

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Harum Khan
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94 views25 pages

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The document provides an introduction to key concepts in bioinformatics including the central dogma of biology, genes, gene expression, high-throughput biological data, protein structure, protein folding, sequence analysis, gene finding, expression data analysis, definitions of life and evolution, and orthology and paralogy. It emphasizes that computational analysis and data mining are essential to effectively utilize the large and growing amounts of biological data being generated.

Uploaded by

Harum Khan
Copyright
© Attribution Non-Commercial (BY-NC)
We take content rights seriously. If you suspect this is your content, claim it here.
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C E N T R E F O R I N T E G R A T I V E

Introduction to bioinformatics
B I O I N F O R M A T I C S V U

High-throughput Biological Data


-data deluge, bioinformatics algorithms-

and evolution

The Central Dogma


Transcription Translation

DNA RNA Protein


The arrows represent the transfer or flow of information.
DNA and RNA store information in a base-4 code (the four nucleotides). Proteins store information in a base-20 code (the 20 amino acids).

Whats in a name?
DNARNA = Transcription
because the information is exactly copied (or transcribed) from one base-4 system (DNA) to an equivalent base-4 system (RNA). Think of a monk transcribing a scroll.

RNAProtein = Translation
because the information is converted from a base-4 system (RNA) to a base-20 system (protein). Think of a monk translating a scroll into a new language.

What is a gene?
A gene is a segment of DNA that contains all the information necessary to code for some function. A gene is also the unit of information that is transferred through Transcription and Translation.

What is a gene?
A gene is a segment of DNA that contains all the information necessary to code for some function. A gene is also the unit of information that is transferred through Transcription and Translation.

Gene expression responds to the environment


ABC

Changes to the cells internal or external environment can lead to changes in gene expression.

ABC

Most human diseases manifest through a mis-regulation of gene expression

Microarrays and related technologies


Gene 1 Gene 2 Gene 3 Gene 4 Gene 5 Gene 6 Gene 7 Gene 8 Gene 9 Gene 10 Gene 11 Gene 12 Gene 13 Gene 14 Gene 15 Gene 16 . . Red 66.29407 52.99309 21.80347 60.59471 27.36376 33.29663 99.12556 57.27299 11.3569 55.1665 10.96976 69.01434 75.822 65.68116 58.42018 10.20642 . . Green 12.2176 73.53539 59.7854 88.49798 97.70567 18.02022 16.0062 85.79522 80.85375 76.82107 77.79816 50.97818 76.47183 6.73611 79.81729 35.2366 . .

Biological Data
Many different genomics datasets:
Genome sequencing: more than 300 species completely sequenced and data in public domain (i.e. information is freely available), virus genome can be sequenced in a day Gene expression (microarray) data: many microarrays measured per day Proteomics: Protein Data Bank (PDB) - as of Tuesday February 07, 2006 there are 35026 Structures. http://www.rcsb.org/pdb/ Protein-protein interaction data: many databases worldwide Metabolic pathway, regulation and signaling data, many databases worldwide

Growth in number of protein tertiary structures

The data deluge


Although a lot of tertiary structural data is being produced (preceding slide), there is the SEQUENCE-STRUCTURE-FUNCTION GAP
The gap between sequence data on the one hand, and structure or function data on the other, is widening rapidly: Sequence data grows much faster

High-throughput Biological Data The data deluge


Hidden in all these data classes is information that reflects
existence, organization, activity, functionality of biological machineries at different levels in living organisms

Most effectively utilising and analysing this information computationally is essential for Bioinformatics

Data issues: from data to distributed knowledge


Data collection: getting the data Data representation: data standards, data normalisation ..

Data organisation and storage: database issues ..


Data analysis and data mining: discovering knowledge, patterns/signals, from data, establishing associations among data patterns Data utilisation and application: from data patterns/signals to models for bio-machineries Data visualization: viewing complex data Data transmission: data collection, retrieval, ..

Bio-Data Analysis and Data Mining


Analysis and mining tools exist and are developed for: DNA sequence assembly Genetic map construction Sequence comparison and database searching Gene finding Gene expression data analysis Phylogenetic tree analysis, e.g. to infer horizontallytransferred genes Mass spectrometry data analysis for protein complex characterization

Bio-Data Analysis and Data Mining


As the amount and types of data and their cross connections increase rapidly the number of analysis tools needed will go up exponentially if we do not reuse techniques
blast, blastp, blastx, blastn, from BLAST family of tools (we will cover BLAST later) gene finding tools for human, mouse, fly, rice, cyanobacteria, .. tools for finding various signals in genomic sequences, protein-binding sites, splice junction sites, translation start sites, ..

Bio-Data Analysis and Data Mining


Many of these data analysis problems are fundamentally the same problem(s) and can be solved using the same set of tools e.g.

clustering or
optimal segmentation by Dynamic Programming

Bio-data Analysis, Data Mining and Integrative Bioinformatics


To have analysis capabilities covering a wide range of problems, we need to discover the common fundamental structures of these problems; HOWEVER in biology one size does NOT fit all

An important goal of bioinformatics is development of a data analysis infrastructure in support of Genomics and beyond

Protein structure hierarchical levels


PRIMARY STRUCTURE (amino acid sequence) VHLTPEEKSAVTALWGKVNVDE VGGEALGRLLVVYPWTQRFFE SFGDLSTPDAVMGNPKVKAHG KKVLGAFSDGLAHLDNLKGTFA TLSELHCDKLHVDPENFRLLGN VLVCVLAHHFGKEFTPPVQAAY QKVVAGVANALAHKYH SECONDARY STRUCTURE (helices, strands)

QUATERNARY STRUCTURE (oligomers)

TERTIARY STRUCTURE (fold)

Protein folding problem


PRIMARY STRUCTURE (amino acid sequence) VHLTPEEKSAVTALWGKVNVDE VGGEALGRLLVVYPWTQRFFE SFGDLSTPDAVMGNPKVKAHG KKVLGAFSDGLAHLDNLKGTFA TLSELHCDKLHVDPENFRLLGN VLVCVLAHHFGKEFTPPVQAAY QKVVAGVANALAHKYH

Each protein sequence knows how to fold into its tertiary structure. We still do not understand exactly how and why
SECONDARY STRUCTURE (helices, strands)

1-step process 2-step process

TERTIARY STRUCTURE (fold)

The 1-step process is based on a hydrophobic collapse; the 2-step process, more common in forming larger proteins, is called the framework model of folding

Sequence analysis and homology searching

Finding genes and regulatory elements

There are many different regulation signals such as start, stop and skip messages hidden in the genome for each gene, but what and where are they?

Expression data

What is life?
NASA astrobiology program: Life is a self-sustained chemical system capable of undergoing Darwinian evolution

Evolution
Four requirements: Template structure providing stability (DNA) Copying mechanism (meiosis) Mechanism providing variation (mutations; insertions and deletions; crossing-over; etc.) Selection: some traits lead to greater fitness of one individual relative to another. Darwin wrote survival of the fittest
Evolution is a conservative process: the vast majority of mutations will not be selected (i.e. will not make it as they lead to worse performance or are even lethal) this is called negative (or purifying) selection

Orthology/paralogy

Orthologous genes are homologous (corresponding) genes in different species Paralogous genes are homologous genes within the same species (genome)

Consequence of evolution
Notion of comparative analysis (Darwin) What you know about one species might be transferable to another, for example from mouse to human Provides a framework to do the multi-level large-scale analysis of the genomics data plethora

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