Lecture 1b Bioinformatics PDF

BME 454 2024-2025 The Foundation of Bioinformatics Prof. Doaa Abdelmonsif Medical Biochemistry &Molecular Biology Alexandria Faculty of Medicine Data (= Raw Data) Data is raw, unorganized facts need to be processed. Example: Each student...

BME 454 2024-2025 The Foundation of Bioinformatics Prof. Doaa Abdelmonsif Medical Biochemistry &Molecular Biology Alexandria Faculty of Medicine Data (= Raw Data) Data is raw, unorganized facts need to be processed. Example: Each students test score is one piece of data. Information (= Analyzed Data) When data is processed, organized structured or presented in a given context to make it useful it is called information. Genetic information is stored in the cell in the form of biological macromolecules, such as Nucleic acids (DNA& RNA) Proteins. The genetic information drives the functioning of the whole organism, drives the evolutionary engine. Data  “Bioinformatics is the application of computers to the collection, archiving, organization, and analysis of biological What is data.” … Bioinformatics is a hybrid of biology and computer science Bioinformatics? … Bioinformatics is computer aided biology!  Bioinformatics is concerned with understanding how basic biological systems collaborate to create molecules, organelles, living cells, organs, and entire organisms. Bioinformatics entails: 1. Creation & advancement of databases, algorithms, computational & statistical techniques. 2. Creation and advancement of theory to solve formal and practical problems arising from the management and analysis of biological data. DNA is the nature’s universal information storage medium Major types of Bioinformatics Data Goal of Bioinformatics: Integrate sequence, 3D structure of protein, gene expression patterns, interaction and function of biomolecules to gain a deeper understanding of biological mechanisms, process and systems.  The first aim, bioinformatics organize data in a way that Aims of allows researchers to access existing information and to submit new entries as they are produced. bioinformatics The second aim is to develop tools and resources that aid in the analysis of data. For example, having sequenced a particular protein, it is of interest to compare it with previously characterized sequences The third aim is to use these tools to analyze the data and interpret the results in a biologically meaningful manner. Where did bioinformatics come from? Bioinformatics arose as molecular biology began to be transformed by the emergence of molecular sequence and structural data Recap: The key dogmas of molecular biology DNA sequence determines protein sequence. Protein sequence determines protein structure. Protein structure determines protein function. Regulatory mechanisms (e.g. gene expression) determine the amount of a particular function in space and time. Relationship between DNA sequence, protein amino acid sequence and 3D protein structure After Human Genome Project (1990 to 2003) there was an information explosion… 3 billion bases 30,000 genes http://www.genome.gov/ Metabolites Levels of protein structure Proteins are polypeptides that have a three-dimensional (3D) structure. They can be described through four different levels of structure. Figure. Schematic diagram representing complexity of genomic data processing. Analysis and interpretation of biological data considers information at every level [Some] Research Projects The Human Genome Project -- old news International HapMap Project -- www.hapmap.org The 1000 Genomes Project – www.1000.genomes.org Encyclopedia of DNA Elements (ENCODE) Project The Cancer Genome Atlas (TCGA) Human Microbiome Project (HMP) – www.hmpdacc.org The eMERGE (Electronic Medical Records and Genomics) Network Challenges Volume of data is staggering How to organize, store and collect sequence information? How to analyze and display the data Automated algorithms needed Clusters, profiles, etc. Sequence data is meaningless without context Not well suited to printed medical record From here the need for bioinformatics has arisen BIOINFORMATICS RESEARCH AREAS Include but are not limited to: 1. Organization, classification, dissemination and analysis of biological and biomedical data (particularly ‘-omics' data). 2. Biological sequence analysis and phylogenetics. 3. Genome organization and evolution. 4. Regulation of gene expression and epigenetics. 5. Biological pathways and networks in healthy & disease states. 6. Protein structure prediction from sequence. 7. Modeling and prediction of the biophysical properties of biomolecules for binding prediction and drug design. 8. Design of biomolecular structure and function (ex, synthetic proteins). With applications to Biology, Medicine, Agriculture and Industry How do we do Bioinformatics? A “bioinformatics approach” involves the application of computer algorithms, computer models and computer databases with the broad goal of understanding the action of both individual genes, transcripts, proteins and large collections of these entities. DNA RNA Protein Genome Transcriptome Proteome  In computer programming terms, an algorithm is a set of well-defined instructions to solve a particular problem. It takes a set of input(s) and produces the desired output. For example, An algorithm to add two numbers: 1. Take two number inputs 2. Add numbers using the + operator 3. Display the result What is an Algorithm? 21 Bioinformatics is an emerging interdisciplinary research area It is a field of science in which biology/medicine, computer science/IT and math/statistics merge into a single discipline. Biologists collect molecular data: DNA & Protein sequences, gene expression, etc. Bioinformaticians Study biological questions by analyzing molecular data Computer & Math scientists (+Mathematicians, Statisticians, etc.) Develop databases, software, algorithms to store and analyze the data. How do we actually do Bioinformatics? Pre-packaged tools and databases ‣ Many online ‣ New tools and time-consuming methods frequently require downloading ‣ Most are free to use Tool development ‣ Mostly on a UNIX environment ‣ Knowledge of programing languages frequently required (Python, Perl, R, C Java, Fortran) ‣ May require specialized or high-performance computing resources (ex, supercomputers)…  Skepticism & Bioinformatics We have to approach computational results the same way we do wet-lab results: Do they make sense? Is it what we expected? Do we have adequate controls, and how did they come out? Modeling is modeling, but biology is different... What does this model actually contribute? Avoid the miss-use of ‘black boxes’ Common problems with Bioinformatics Confusing multitude of tools available ‣ Each with many options and settable parameters Most tools and databases are written by and for nerds ‣ Same is true of documentation - if any exists! Most are developed independently Notable exceptions are found at the: EBI (European Bioinformatics Institute) and NCBI (National Center for Biotechnology Information) Even Blast has many settable parameters Related tools with different terminology 30  Key online bioinformatics resources NCBI : National Centre for Biotechnology Information (USA) EMBL-EBI : European Molecular Biology Lab -European bioinformatics institute DDBJ : DNA Data Bank of Japan  Key Online Bioinformatics Resources: NCBI & EBI The NCBI and EBI are invaluable, publicly available resources for biomedical research http://www.ncbi.nlm.nih.gov https://www.ebi.ac.uk 1. National Center for Biotechnology Information (NCBI) Created in 1988 as a part of theNational Library of Medicine (NLM) at the National Institutes of Health NCBI’s mission includes: ‣ Establish public databases ‣ Develop software tools ‣ Education on and dissemination of biomedical Bethesda,MD information We will cover a number of core NCBI databases and software tools in the lecture http://www.ncbi.nlm.nih.gov http://www.ncbi.nlm.nih.gov  http://www.ncbi.nlm.nih.gov Notable NCBI databases include: GenBank, RefSeq, PubMed, dbSNP and the search tools ENTREZ and BLAST  Key Online Bioinformatics Resources: NCBI & EBI The NCBI and EBI are invaluable, publicly available resources for biomedical research http://www.ncbi.nlm.nih.gov https://www.ebi.ac.uk 2. European Bioinformatics Institute (EBI) Created in 1997 as a part of the European Molecular Biology Laboratory (EMBL) EBI’s mission includes: ‣ providing freely available data and bioinformatics services ‣ and providing advanced Hinxton,UK bioinformatics training We will briefly cover several EBI databases and tools that have advantages over those offered at NCBI  The EBI maintains a number of high quality curated secondary databases and associated tools  The EBI maintains a number of high quality curated secondary databases and associated tools  The EBI maintains a number of high quality curated secondary databases and associated tools  https://www.ebi.ac.uk The EBI makes available a wider variety of online tools than NCBI These include multiple tools in the following areas: Database sequence searches ‣ FASTA, BLAST, InterProScan Sequence alignments ‣ Pairwise: Needle, LAlign. ‣ Multiple: ClustalW, T-Coffee, MUSCLE, Jalview Protein structure search and alignment ‣ PDBeFold, DALI and others... ‣ Genome browsers ‣ Gene expression analysis ‣ Protein function analysis The EBI also provides a growing selection of online tutorials on EBI databases and tools The EBI also provides a growing selection of online tutorials on EBI databases and tools The EBI also provides a growing selection of online tutorials on EBI databases and tools Notable EBI databases include: ENA, UniProt, Ensembl and the tools FASTA, BLAST, InterProScan, ClustalW, T-Coffee, MUSCLE, DALI, HMMER Bioinformatics vs Computational Biology Bioinformatics: Relation to Artificial Intelligence Artificial intelligence (AI) has increasingly gained attention in bioinformatics research and computational molecular biology. 1. Artificial intelligence Algorithms to be used for keeping records 2. Choosing a particular method for analyzing data 3. Helping Interpret Large Amount of Data quickly by using computer Technology