Introduction to Clinical Bioinformatics and Genomics (Online)

BIOL60100 Introduction to Clinical Bioinformatics and Genomics (Online) 15 Variable teaching patterns Postgraduate Taught Level 6 School of Biological Sciences 1 FHEQ level (Framework for Higher Education Qualifications) ' Masters/Integrated Masters P4 ' European Credit Transfer & Accumulation System Rating : 7.5 This module will provide students with a background knowledge of human genomics, with a particular emphasis on the application to the clinical setting. We will focus on the application of next generation sequencing technologies in the clinic and how they are transforming patient care. We will introduce the basic concepts of next generation sequencing and how the resulting genomic data is analysed. We will introduce bioinformatics tools, databases and the methodology that will help to make sense of all of this clinical genomic data.  Introduction to Clinical Bioinformatics and GenomicsGenetics/Genomics <ul style="list-style-type: circle"> <li> Introduction to the history and scope of genomics</li> <li> The Genome Landscape</li> <li> Nucleic Acid structure and function, including the structure and function of coding and non-coding DNA</li> <li> The central dogma</li> <li> From DNA, to RNA and proteins</li> <li> Noncoding regulatory sequence: promoters, transcription factor binding sites, splice site dinucleotides, enhancers, insulators, epigenetics Mendelian inheritance</li> <li> Genomicvariation and its role in health and disease</li> <li> Genomic technology and role of the genome in the development and treatment of disease</li> </ul> Sequencing <ul style="list-style-type: circle"> <li> Types of sequencing, applications and limitations; Sanger versus short read versus long read</li> <li> Analysis, annotation and interpretation of next generation sequencing (NGS) data</li> <li> Gene panels versus exomes versus whole genomes</li> <li> Quality, depth and coverage considerations in NGS</li> </ul>  Bioinformatic Fundamentals <ul style="list-style-type: circle"> <li> Introduction to the history and scope of bioinformatics</li> <li> Primary biological sequence resources, including INDSC (GenBank, EMBL, DDBJ) and UniProt (SwissProt and TrEMBL)</li> <li> Genome browsers and interfaces; including Ensembl, UCSC Genome Browser, Entrez,</li> <li> Similarity/homology, theory of sequence analysis, scoring matrices, dynamic programming methods including BLAST, pairwise alignments(e.g., Smith Waterman, Needleman Wunsch), multiple sequence alignments (e.g., ClustalW, T-Coffee, Muscle), BLAT</li> <li> Feature identification including SNP analysis and transcription factor binding sites and their associated TF binding sequence motifs</li> <li> Ontologies – in particular GO, Human Phenotype Ontology (HPO)</li> </ul>  Clinical application of bioinformatics Introduction to the clinical application of bioinformatic resources, including their role and use in a clinical context. <ul> <li> Genome browsers</li> <li> Variant databases</li> <li> Phenotype databases</li> <li> Missense and splice site prediction tools</li> <li> Locus specific databases</li> <li> CNV analysis tools</li> </ul>  Ethics, standards and governance <ul> <li> Genomic nomenclature</li> <li> Sequence files and formats</li> <li> Variant files and formats</li> <li> Variant classification</li> <li> Iso standards</li> <li> Data protection and governance for genomic data</li> <li> Incidental findings in genomic data</li> </ul> This module will provide students with a background knowledge of human genomics, with a particular emphasis on the application to the clinical setting. We will focus on the application of next generation sequencing technologies in the clinic and how they are transforming patient care. We will introduce the basic concepts of next generation sequencing and how the resulting genomic data is analysed. We will introduce bioinformatics tools, databases and the methodology that will help to make sense of all of this clinical genomic data <ol> <li> Discuss the governance and ethical frameworks in place within the NHS and how they apply to bioinformatics.</li> <li> Discuss and justify the importance of standards, best practice guidelines and standard operating procedures: how they are developed, improved and applied to clinical bioinformatics.</li> <li> Describe the structure of DNA and the functions of coding and non-coding DNA.</li> <li> Discuss the flow of information from DNA to RNA to protein in the cell.</li> <li> Describe transcription of DNA to mRNA and the protein synthesis process.</li> <li> Understand the process of meiosis and mitosis, inheritance and de novo mutations.</li> <li> Discuss the role of variants in Mendelian and complex disorders and give examples of variants involved in genetic disease.</li> <li> Describe appropriate bioinformatics databases capturing information on DNA, RNA and protein sequences.</li> <li> Explain the theory of sequence analysis and the use of genome analysis tools.</li> <li> Describe the reference genome.</li> <li>  Explain fundamental bioinformatic principles, including the scope and aims of bioinformatics and its development.</li> <li>  Discover resources linking variants to disease processes and discuss and evaluate the resources that are available to the bioinformatician and how these are categorised. Identify appropriate references where published data are to be reported.</li> <li value="13"> Describe the biological background to diagnostic genomic testing and clinical genomics, and the role of bioinformatics.</li> <li> Describe the partnership of Clinical Bioinformatics and Genomics to other clinical specialisms in the investigation and management of genetic disorders and the contribution to safe and effective patient care</li> </ol> <ol> <li> Critically analyse scientific and clinical data</li> <li> Present scientific and clinical data appropriately</li> <li> Formulate a critical argument</li> <li> Evaluate scientific and clinical literature</li> <li> Apply the knowledge of clinical bioinformatics to address specific clinical problems</li> </ol> <ol> <li>  Present information clearly in the form of written reports.</li> <li> Communicate complex ideas and arguments in a clear and concise and effective manner.</li> <li> Work effectively as an individual and part of a team.</li> <li> Use relevant literature and electronic resources to collect, select and organise complex scientific information</li> <li> Perform analysis on DNA data and protein sequence data to infer function.</li> <li> Perform sequence alignment tasks.</li> <li> Select and apply appropriate bioinformatic tools and resources from a core subset to typical diagnostic laboratory cases, contextualised to the scope and practice of a clinical genetics laboratory.</li> <li> Compare major bioinformatics resources for clinical diagnostics, and how their results can be summarised and integrated with other lines of evidence to produce clinically valid reports.</li> <li> Interpret evidence from bioinformatic tools and resources and integrate this into the sum of genetic information for the interpretation and reporting of test results from patients.</li> <li> Perform the recording of building or version numbers of resources used on a given date, including those of linked data sources, and understand the clinical relevance of this data.</li> </ol> <ol> <li>  Present complex ideas in simple terms in written formats.</li> <li value="2"> Actively seek accurate and validated information from all available sources. </li> <li value="3"> Interpret data and convert into knowledge for use in the clinical context of individual and groups of patients.</li> <li> Work in partnership with colleagues, to create clinical reports suitable for presentation to a clinician.</li> </ol> 0 Other 20% 3 Report 30% 7 Oral assessment/presentation 50% PGCert Clinical Bioinformatics PGCert Clinical Bioinformatics PGDT Taught Component Mandatory N Molecular Biology/Genetics textbooks – look for the latest edition <ol> <li> Human Molecular Genetics, Tom Strachan and Andrew Read, Garland Science Chapters 1, 2 and 13</li> <li> New Clinical Genetics, Andrew Read and Dian Donnai, Scion Publishing</li> </ol> Journal papersGenetics <ol> <li value="3"> What is a gene, post ENCODE? History and updated definition</li> </ol> Gerstein, MB et al (2007) Genome Research 17:p669 https://doi.org/10.1101/gr.6339607 <ol> <li value="4"> Non-coding RNAs: key regulators of mammalian transcription</li> </ol> Kugel, JF and Goodrich, JA (2012) Trends Biochem Sci 37(4):p144 <a href="https://doi.org/10.1016/j.tibs.2011.12.003">https://doi.org/10.1016/j.tibs.2011.12.003</a> <ol> <li value="5"> <a href="http://www.nature.com/scitable/topicpage/regulation-of-mrna-splicing-by-signal-transduction-14128469">http://www.nature.com/scitable/topicpage/regulation-of-mrna-splicing-by-signal-transduction-14128469</a></li> <li value="6"> RNA splicing, disease and therapy https://doi.org/10.1093/bfgp/elr020</li> </ol>  Variant interpretation <ol> <li value="7"> Standards and guidelines for variant interpretation doi:10.1038/gim.2015.30</li> <li value="8"> Human genotype:phenotype databases https://doi.org/10.1038/nrg3932</li> </ol> 150