Introduction to Clinical Bioinformatics
This section covers the division/theme-specific module that will be studied by all trainees undertaking the Clinical Bioinformatics STP.
Within this curriculum examples of commercially available software are provided to illustrate the learning outcome/competence. Please note these examples are not exhaustive and other appropriate software can be used, and
any commercially available software included does not imply that this is recommended for use by the authors.
Division: Cross-Divisional Theme: Bioinformatics
Year 1: Introduction to Clinical Bioinformatics [40 credits]
The overall aim of this module is to provide trainees with the knowledge that underpins the STP work based rotational programme in Clinical Bioinformatics. A high-level description of the work based placed learning is included to provide education providers with information on how the academic and work based elements integrate.
Rotational Programme
Division: Cross-Divisional
Theme: Clinical Bioinformatics
Rotation A: Introduction to Clinical Bioinformatics and Genetics [10 credits]
Rotation B: Computing for Clinical Scientists [10 credits] Rotation C: ICT in the Clinical Environment [10 credits] Rotation D: Introduction to Health Informatics [10 credits]
Rotation A: Introduction to Clinical Bioinformatics and Genetics [10 credits]
This rotation will provide trainees with background knowledge of genetics and a knowledge and understanding of bioinformatics tools and infrastructure. In particular it will show how bioinformatics strategies can be used and applied to genomic and genetic data to generate information and knowledge that contributes to patient care and care pathways within a clinical setting. It will also introduce the ethical and governance framework appropriate for working with patient data in an NHS setting.
Learning Outcomes: Knowledge and Understanding On successful completion of this module the trainee will:
1. Discuss the governance and ethical frameworks in place within the NHS and how they apply to bioinformatics.
2. Discuss and justify the importance of standards, best practice guidelines and standard operating procedures: how they are developed, improved and applied to clinical bioinformatics.
3. Describe the structure of DNA and the functions of coding and non-coding DNA.
4. Discuss the flow of information from DNA to RNA to protein in the cell. 5. Describe transcription of DNA to mRNA and the protein synthesis process. 6. Discuss the role of polymorphisms in Mendelian and complex disorders and
give examples of polymorphisms involved in genetic disease.
7. Describe appropriate bioinformatics databases capturing information on DNA, RNA and protein sequences.
8. Explain the theory of sequence analysis and the use of genome analysis tools.
9. Describe secondary databases in bioinformatics and their use in generating metadata on gene function.
10. Explain fundamental bioinformatic principles, including the scope and aims of bioinformatics and its development.
11. Explain fundamental genomic principles, including the scope and aims of genomics and its development.
12. Discover resources linking polymorphism to disease processes and discuss and evaluate the resources that are available to the bioinformatician and how these are categorised.
13. Discuss metadata and how it is captured in bioinformatics resources. 14. Interpret the metadata provided by the major bioinformatics resources. 15. Describe the use of ontologies in metadata capture and give examples of
the use of ontologies for capturing information on gene function and phenotype.
16. Identify appropriate references where published data are to be reported. 17. Describe the biological background to diagnostic genetic testing and clinical
genetics, and the role of bioinformatics.
18. Describe the partnership of Clinical Bioinformatics and Genetics with other clinical specialisms in the investigation and management of genetic
disorders and the contribution to safe and effective patient care. Learning Outcomes: Associated Work Based Learning
High-level description of the work based learning that accompanies this academic module. Further details of the work based programme can be found in the Work Based Learning Guide, including the Clinical Experiential Learning, Competences and Applied Knowledge and Understanding.
On successful completion of this module the trainee will:
1. Perform analysis on DNA data and protein sequence data to infer function. 2. Perform sequence alignment tasks.
3. 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.
4. 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.
5. 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.
6. 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.
Indicative Content Genetics/Genomics
• Introduction to the history and scope of genomics
• The Genome Landscape
• The structure and function of coding and non-coding DNA
• The central dogma
• From DNA, to RNA and proteins
• Non-coding regulatory sequence: promoters, transcription factor binding sites, splice site dinucleotides, enhancers, insulators
• Genetic variation and its role in health and disease Sequencing
• Types of sequencing, applications and limitations; Sanger versus short read
• Analysis, annotation and interpretation
• Panel versus exome versus whole-genome resequencing Statistics
• Basic statistics applied to clinical genetics/genomics
• Hardy-Weinberg, Bayes theorem, risks in pedigrees Bioinformatic fundamentals
• Introduction to the history and scope of bioinformatics
• Primary biological sequence resources, including International Nucleotide Sequence Database Collaboration (INSDC) (GenBank, EMBL, DDBJ) and UniProt (SwissProt and TrEMBL)
• Genome browsers and interfaces, including Ensembl, University of California, Santa Cruz (UCSC) Genome Browser, Entrez
• Similarity/homology, theory of sequence analysis, scoring matrices, dynamic programming methods, including Basic Local Alignment Search Tool
(BLAST), pairwise alignments (e.g. Smith Waterman, Needleman Wunsch), multiple sequence alignments (e.g. ClustalW, T-Coffee, Muscle), BLAT (BLAST-like Alignment Tool)
• Feature identification, including single-nucleotide polymorphism (SNP) analysis and transcription factor binding sitesand their associated TF binding sequence motifs
• Ontologies – in particular Genoe Ontology (GO), Human Phenotype Ontology (HPO)
Clinical application of bioinformatics
• Introduction to the clinical application of bioinformatic resources, including its role and use in a medical context in molecular genetics, cytogenetics and next generation sequencing for data manipulation and analysis, and
• Background and application of specialist databases and browsers
o Single-Nucleotide Polymorphism Database (dbSNP) o DECIPHER
o Orphanet
o Diagnostic Mutation Database (DMuDB)/NGRL Universal Browser o ClinVar (http://www.ncbi.nlm.nih.gov/clinvar/intro/)
o OMIM o ECARUCA
o Database of Genomic Variants (DGV)
o Leiden Open (Source) Variation Database (LOVD)/Universal Mutation
database (UMD) database software and scientific literature
o Human Gene Mutation Database (HGMD)
• Specific clinical analysis software
o CNV analysis
o Gene prioritisation (e.g. ToppGene, Endeavour, GeCCO)
o Missense analysis (e.g. Align GVGD, SIFT, PolyPhen, Panther,
PhDSNP, MAPP)
o Splicing analysis applications (e.g. GeneSplicer, MAxEntScan,
NNSplice, SSFL, HSF, NetGene2)
o Commercially available software (e.g. NextGENe, Alamut, Cartegenia)
• Capture and representation of phenotype data
• Development of a simple application for clinical bioinformatic use Standards and governance
• Data standards and formats
o International Union of Pure and Applied Chemistry (IUPAC) codes o FASTA
o GenBank o FASTQ
o Sequence Alignment/Map (SAM)/ Binary Alignment/Map (BAM)/CRAM o Visual Component Framework (VCF)
o Human Genome Variation Society (HGVS) variant nomenclature
o Human Genome Nomenclature Committee (HGNC) gene nomenclature o RefSeq/RefSeqGene
o Locus Reference Genomic (LRG)
• Role and development of standard operating procedures
• Relevant standards (clinical, genetic, bioinformatic) for data representation and exchange
Rotation B: Computing for Clinical Scientists [10 credits]
Modern healthcare generates large amounts of data – data that must be managed and shared effectively. In many cases this will involve staff working with database systems and interacting with internal or external computer scientists/software engineers to commission appropriate data management tools. In this module trainees will be introduced to the fundamental aspects of computer science needed to support data management. They will also be introduced to the principles of modern software engineering processes such that they can better engage with and support software development within the NHS.
Learning Outcomes: Knowledge and Understanding On successful completion of this module the trainee will:
1. Describe the basic features of the Windows and UNIX operating systems. 2. Discuss client/server architectures.
3. Describe the basics of a relational database system and data normalisation. 4. Interpret a range of structured query language (SQL) commands.
5. Describe a number of commonly used mark-up languages.
6. Interpret simple HyperText Markup Language (HTML) scripts and simple Extensible Markup Language (XML) scripts.
7. Critically appraise the functional and non-functional requirements for a system.
8. Discuss the advantages and disadvantages of Unified Modelling Language (UML) for capturing requirements.
9. Discuss the role of application programming interfaces (APIs) in allowing systems to communicate.
10. Give examples of software allowing databases to communicate with web browsers, e.g. Simple Object Access Protocol (SOAP), Common Gateway Interface (CGI).
11. Discuss security issues around client server systems and system security in the context of NHS data governance and ethics concerns.
12. Discuss and describe different software engineering models, e.g. agile, waterfall.
13. Discuss how database systems/data management and modern software processes contribute to patient care pathways and the provision of high- quality safe and effective patient care.
14. Describe software quality assurance processes. Learning Outcomes: Associated Work Based Learning
High-level description of the work based learning that accompanies this academic module. Further details of the work based programme can be found in the Work Based Learning Guide, including the Clinical Experiential Learning, Competences and Applied Knowledge and Understanding.
On successful completion of this module the trainee will:
1. Plan a process and assemble the requirements for a clinical information system.
2. Express system requirements in UML.
3. Design a relational database system for a clinical information system, ensuring an appropriate level of data normalisation.
4. Build an information system allowing web access to an SQL database. 5. Construct a range of appropriate SQL commands.
6. Complete the project documentation, ensuring compliance with security, governance and ethics issues with web-accessible database systems.
Operating systems
• Different common operating systems, e.g. Windows, Linux
• An introduction to file management, security, user management
• Basic principles relating to information communications technology (ICT) security, including firewalls, virus protection, encryption, server access and data security
The web
• How TCP/IP works
• Client server architectures
• HTML
Database theory
• Capturing requirements – the idea of use cases
• Basic introduction to SQL
• Basic introduction to theory of normalisation
• Database design in an SQL environment
• APIs for communication with databases Mark-up languages
• HTML and XML
• XML interpretation Security
• Common database security issues
• Governance and ethics associated with information systems in the NHS Software engineering
• Introduction to the concept of the software life cycle and the tools and frameworks used to specify, develop, validate and verify clinical software
• Formal processes for gathering requirements
• Functional and non-functional requirements
• UML and systems modelling
• Effective communication of requirements
• Developing software as a team
• Different software development models: waterfall vs agile
• Managing code effectively – version control systems
Rotation C: ICT in the Clinical Environment [10 credits]
This module introduces the trainee to the application of ICT in the Clinical Environment and provides the knowledge that underpins this rotation*, which is important to the application of bioinformatics in clinical practice. Scientists may also oversee the interconnection of critical patient safety computer systems, e.g. networks planning, imaging, controlling and verifying radiotherapy treatments. It may also include the development of novel image and signal processing applications.
*Initially this rotation is likely to be in a Medical Physics or Clinical Engineering Environment but may be in part or wholly undertaken in a Physiological Sciences department.
Learning Outcomes: Knowledge and Understanding On successful completion of this module the trainee will:
1. Describe and justify the legislation and standards that underpin the safe use of ICT within the clinical environment, including the control of medical devices.
2. Discuss the basis of physiological data capture, presentation and measurement.
3. Discuss the usage of clinical data generated by a medical device. 4. Discuss the basis of image formation, reconstruction and presentation. 5. Discuss the interconnectivity of ICT equipment and computer systems
within the clinical environment.
6. Discuss how database systems/data management and modern software processes contribute to patient pathways and the provision of high-quality safe and effective patient care.
7. Discuss and evaluate the role of the healthcare science workforce and the Clinical Scientist in innovation and service development.
Learning Outcomes: Associated Work Based Learning
High-level description of the work based learning that accompanies this academic module. Further details of the work based programme can be found in the Work Based Learning Guide, including the Clinical Experiential Learning, Competences and Applied Knowledge and Understanding.
On successful completion of this module the trainee will:
1. Observe and assist during a range of clinical measurement procedures effectively and safely with due regard to the patient, health and safety, data security and governance in ICT within the context of your work placement. 2. Develop a prototype image processing application.
3. Manipulate data using a spreadsheet or database environment and an appropriate programming language.
4. Use configuration control in relation to PC software installations and local area networks, including the installation of systems and applications.
Indicative Content Safety
• Health and safety legislation specific to division/workplace • Risk assessment techniques
• Electrical safety; medical equipment, leakage currents, fault conditions, isolation and circuit protection; biological/physiological response to electric shock; treatment of electric shock; equipment testing
• Workshop safety
Information Communications Technology
• Range of general purpose computer software in common use, including spreadsheets, flat-file and structured databases, online reference and collaborative resources
• Computing applied clinically, including the additional safeguards when the computer acts as a medical device. This includes an understanding of the role of the Medicine and Healthcare products Regulatory Agency (MHRA), the Food and Drugs Administration (FDA) and the International
Electrotechnical Commission (IEC) and their role in Conformance European (CE) Marking
• Data exchange standards and an awareness of some of the common standards, e.g. Digital Imaging and Communications in Medicine (DICOM) and Healthcare Level 7 (HL7)
• Networking systems in common clinical use and the role of local trust information technology policies
• Data compression technologies for storage and transmission
• Basic principles of applicable legislation and of local policies, including the Data Protection Act, Computer Misuse Act and Freedom of Information Act Data from medical devices: integrity and processing
• The physiology of pressure, flow, temperature, pH, blood gases, respiratory function and electrophysiology
• The physical principles underpinning these measurements • Transducers for physiological measurement
• Calibration, traceability of standards
• Sources of error: random, systematic and human • Error propagation
• Error analysis
• Sensitivity and specificity of measurement techniques
• Relationship of measurement results to clinical pathology, data processing and interpretation
• Usage of data generated by medical devices and the overview of medical device life cycle
Introduction to imaging
• The physics and mathematics of image formation as it relates to two examples from the list below:
o the radiological image
o computed tomography (CT) scanning
o gamma camera
o positron emission tomography (PET)
o magnetic resonance imaging (MRI)
o ultrasound
• Introduction to image reconstruction techniques • Introduction to image processing and analysis • Image display characteristics
• Clinical application and a basic understanding of normal and pathological appearances within the image
• Introduction to image registration Innovation and service improvement
• Role of ICT in innovation and service improvement • Project management
• Process mapping • Equipment life cycle
• Specification, procurement, installation and commissioning • Critical review of protocols, techniques and equipment • Health Technology Assessment
• Horizon scanning
Rotation D: Introduction to Health Informatics [10 credits]
This rotation will provide trainees with the basic informatics knowledge and understanding of the skills and tools needed by all professionals in modern healthcare systems to provide safe, secure, high-quality, effective patient- centred services. Learning will be developed and applied in the work based training and contextualised to patient care and patient safety.
The content of the module is taken from the national curriculum framework ‘Learning to Manage Health Information: A theme for clinical education 2012 – Making a difference’ (Department of Health 2012). This fourth edition of the framework was developed in partnership with representatives of a wide range of clinical professional bodies, health informatics professionals and health educators from across the UK.
Learning Outcomes: Knowledge and Understanding On successful completion of this module the trainee will:
1. Discuss and justify the legislation, regulatory guidance and national and local protocols relating to the security, confidentiality and appropriate sharing of patient information.
2. Explain the information governance implications for individuals and organisations of information sharing and communication between professions, with patients/clients and across organisations.
3. Discuss the principles and purpose of effective quality control and validation of data and the impact of poor quality data on management and healthcare outcomes. Identify the range, purposes, benefits and potential risks of sharing, integrating and aggregating clinical data and information.
4. Discuss the role of informatics in clinical governance.
5. Describe and evaluate the purpose, structures, use and storage of health and care records.
6. Discuss the implications of patient access to records and clinical information for interprofessional practice and multidisciplinary care.
7. Discuss the basis and application and evaluate the limitations of the different clinical coding systems in use, and the importance of high-quality coded clinical data in communication and to patient safety.
8. Explain the use of clinical terms in record keeping and the role of terming on reporting and analysis.
9. Discuss the importance of ICT in supporting clinical practice and new ways of working in healthcare, drawing on examples from national and local policy strategy.
10. Discuss the risks in clinical IT systems and mitigations.
11. Discuss emerging information and communication technologies and their application in health and care.
Associated Work Based Learning Outcomes
High-level description of the work based learning that accompanies this academic module. Further details of the work based programme can be found in the Work Based Learning Guide, including the Clinical Experiential Learning, Competences and Applied Knowledge and Understanding.
On successful completion of this module the trainee will:
1. Successfully complete the national Information Governance training module (with a score of more than 80%).
2. Perform a clinical audit and produce an audit report.
3. Advise peers and colleagues on best practice in data and information security, patient confidentiality, record sharing, information sharing with patients/clients and records access by patient.
4. Access local and national clinical knowledge bases and care pathway guidance.
5. Send, receive and store communications containing patient/clinical information safely and securely in accordance with policy, protocols, legislation and codes.
6. Perform a review of a local clinical IT system for patient safety and security compliance.
To support the training and development of clinical professionals pre- and post- registration and in response to requests from clinical educators, a suite of seven, short, free, online learning materials have been developed, based on the content of ‘Learning to Manage’. They can be accessed at:
www.cln.nhs.uk/eice. Organisations/academic institutions may register
staff/students on the portal and then track progress using the integral learning management system. Individuals can also register and access the materials. Indicative Content
Information governance: data and information quality, security and confidentiality
• Acts of Parliament, other legislation, Codes of Practice