Bioinformatics - Discovering the Bio Logic Of Nature
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Bioinformatics analyzes vast amounts of genomic and protein sequence data using computers and algorithms to understand the fundamental processes of life. It has become a key tool in biotechnology for applications like drug discovery. While DNA sequences life's code, molecular networks and regulatory interactions are more complex than once thought, with RNA and proteins also playing important roles before and after DNA. Continued advances in sequencing technology and data integration across multiple fields will be needed to fully unravel these biological systems.
![Contact Information Robert D. Cormia Foothill College [email_address] http://www.informaticus.org/ 650 747 1588 Surfing the Genome – Spring 2003](https://image.slidesharecdn.com/bio-logicofnature-090425123941-phpapp02/85/Bioinformatics-Discovering-the-Bio-Logic-Of-Nature-75-320.jpg)
Bioinformatics - Discovering the Bio Logic Of Nature
- 1. Bioinformatics – Discovering the “Bio-Logic” of Nature Robert Cormia Foothill College
- 2. Transducing the Genome 50 years after Watson and Crick deduced the structure of DNA… The information molecules of nature now reside as data bits inside computers But what does it all mean? We have ~15 GBytes of genomic data And only just beginning to unravel it
- 4. ‘ Energy Systems’ Before ‘Life’ “ Life” arose on earth almost 4 billion years ago, 1 billion years before cells Long chains of molecules harvesting energy, probably deep below the sea Before DNA, RNA and the sophisticated proteins that we know today There were plenty of sources of energy, but no “choreographed metabolism”
- 6. “ In the Beginning” Rock, heat, and some water Early molecules of life Energy moved from rock into sea Molecular networks played in the path Capturing a memory of that process was probably the key to life today
- 7. Life on the Sea Floor?
- 8. RNA Busy Before Cellular Life
- 9. The RNA World There is no way to know how the molecules of life really formed… Amino acids and ribonucleotides have formed in “pre-biotic” experiments RNA molecules, which appear to be both catalysts and templates, are thought to have formed energy networks
- 10. RNA Codons and Catalysts
- 11. RNA and DNA A, T, C, G, and U A = Adenine T = Thymine C = Cytosine G = Guanine U = Uracil A-T and C-G in DNA A-U and C-G in RNA
- 12. Central Dogma of Life
- 13. The Genome DNA – D eoxyribo N ucleic A cid is the prominent molecule of the genome Genes are formed of lengths of DNA polymers which code for proteins Exons and introns exist in DNA Regulatory regions control transcription and the formation of every protein and enzyme. It is the key to metabolism.
- 16. The Proteome Proteins form cellular structure and enzymes, which function in metabolism Over 100,000 proteins exist in humans DNA is not enough to run metabolism Proteins have a “run-time” knowledge Proteins control the transcription of DNA and DNA controls formation of proteins
- 17. Rubisco Protein – Photosynthesis
- 19. Number of Genes vs. Time
- 20. What is Bioinformatics? Molecular biology Ability to sequence DNA Internet databases To store and transmit data Mathematical algorithms To model and solve biological problems Analysis Using the I2I Technology Model
- 21. Internet Technologies CPU Networking Data Storage Data Mining Grid Computing Storage Area Networks
- 22. Bioinformatics Technologies Informatics IT / Networking Molecular Biology Data Modeling Computational Biology Genomic Databases
- 23. A Tool for Biotechnology Bioinformatics creates a set of tools for understanding the mountain of new data In biotechnology, these tools are used to discover how genes and proteins work Computers are used to both analyze and “mine” new data for hidden relationships Discovering the “bio-logic” of nature
- 24. From Data to Knowledge
- 25. DNA Sequencing
- 26. DNA Sequencing Chemical sequencing Molecular sequencing Now about $0.01 per base Human Genome took 10 years Celera sequenced in 3 years Moore’s law applies to biotechnology too In 2010 a single human genome in ~7 days
- 29. DNA Micro Arrays Used to monitor gene expression Which genes are active? What are the “co-expressed patterns”? Compare healthy and diseased tissue Extract “expressed” mRNA in cytoplasm Convert mRNA to cDNA Discover relationships of proteins to disease states, and function / location of genes Is becoming the first step in “drug-discovery”
- 32. Partnering with Pharma Bioinformatics is an industry of tools Biotech is a consumer / user of these tools Pharma needs more “innovation engines” Less than 2 drugs per firm in the ‘pipeline’ Drug discovery creates a new value chain bioinformatics > biotech > ‘big pharma’ Convergence is the modality of innovation
- 34. Drug Discovery Target discovery Target validation Protein interactions Rapid screening The long haul… $800 million / year is spent on drug discovery Over 75% of drug compounds will never work
- 36. Drug Discovery
- 37. “ Pharmaco Genomics” Individualized medicine Looking at SNPs along drug targets What makes each of us – us? 1 million SNPs, about one per intron In the future, each of us will have our genome “insilico” (genome on a chip) Data mining against 6 billion genomes!
- 39. One Genome There are three very different ways to look at genomic diversity – and all are equally valid! A “collective” human genome 3 billion base pairs – called the ‘golden path’ Each one of us is a unique genome “ I am a genome of one”, my SNPS make me - ‘me’ The Genome on planet earth A collective metabolic evolution and speciation
- 40. Terra Genoma
- 41. Molecular Networks Genome or Proteome? Proteome of Genome? Wait a minute… What if it’s both? Now what would that look like?
- 44. Pathway Kinetics
- 46. Bioinformatics Tools NCBI BLAST, 12 million records, SNP databases ExPASy Swiss-Prot, EMBL, Swiss-Model PIR – Protein Information Resource PDB – Protein Data Bank Pfam – Protein families
- 47. NCBI National Center for Biotechnology Information, part of NIH and NLM Funded by US – open to all GenBank and GenPept 13 million entries, 12 billion base pairs Resources include oncology, retroviruses, SNP databases, and much more Sequin submission of raw sequence data
- 49. NCBI Resources
- 50. Retroviruses
- 51. BLAST Basic Local Alignment Search Tool Used as a “genomic search engine” Compare your target sequence to the “non-redundant” database of 13B bps. Can search the genomes of species Human, mouse, fly, E.coli etc. ‘ Hits’ return inks to GenBank and GenPept
- 53. Swiss-Prot Swiss - protein annotated database Protein resource Minimal redundancy, reasonably current protein annotated / integrated database Links to protein structures and properties Links back into GenBank, EMBL, DDBJ Literature resources for submissions
- 54. ExPASy The ExPASy ( Ex pert P rotein A nalysis Sy stem) Proteomics server of the Swiss Institute of Bioinformatics (SIB) is dedicated to analysis of protein sequences and structures Swiss-Prot and PROSITE Links to SWISS-MODEL
- 55. PROSITE - Database of Protein Families and Domains
- 57. Protein Data Bank SWISS-MODEL Protein Data Bank Archive of .pdb files Structures determined by X-ray, NMR Theoretical Structure Search Features a “Molecule of the Month” http://www.rcsb.org/pdb/
- 59. PIR Protein Information Resource i ProClass and PRI-NREF PIR-PSD, Swiss-Prot, TrEMBL, RefSeq, GenPept, and PDB http://pir.georgetown.edu/ Integrated public resource of protein informatics Supports genomic and proteomic research and scientific discovery - i ProClass and PRI-NREF
- 61. Pfam Protein family comparisons Look at multiple alignments View protein domain architectures Examine species distribution Follow links to other databases View known protein structures Follow ‘conserved domains’ from BLASTp searches of protein databases
- 64. The Technology Roadmap Genomics 1995 to 2005 Proteomics 2000 to 2010 Systems biology 2005 to 2015 Genetic remodeling / re-engineering 2010 to 2020 Generation Phi Children born in 2025 may never know disease
- 65. Convergence of Biotech & Pharma Genomics Proteomics Systems biology Pharmaco genomics Genetic engineering
- 66. Mouse Genome
- 68. Gene Therapy Somatic Gene Therapy Therapeutic Gene Therapy Incorporate “missing genes” Remove cells from host organism Amplify target cells Insert gene using (viral) vector Return target cells into host organism Insulin gene was one of the first trials
- 70. Labeling Active Genes Along Chromosomes
- 72. Designer Flies – Is Blue Cool?
- 73. Your Own Private Genome
- 74. Surfing the Genome Internet technologies Connecting users, tools, and data Molecular biology Racing forward a top Moore’s Law Informatics Mathematical interrogation of nature’s secrets Surfing the Genome! Discovering the “bio-logic” of Nature http://www.SurfingTheGenome.us/ Spring 2003
- 75. Contact Information Robert D. Cormia Foothill College [email_address] http://www.informaticus.org/ 650 747 1588 Surfing the Genome – Spring 2003