Bioinformatics AssignmentHuman Genomic Databases
Bioinformatics AssignmentHuman Genomic Databases
Due Date: 3rd May 2024 at 23:59
Purpose
The purpose of this assignment is to become familiar with several different human genomics databases, the information they contain, and the tools they provide to interrogate that information. Medical Laboratory Scientists regularly use these, and other, human genomic databases in the course of their work to interpret the results of genetic diagnostic and screening tests. Specifically, they use these databases to determine the probability that genomic variants that have been observed in test samples will adversely affect the function of gene products and could therefore be considered pathogenic (causative of disease).
This assignment will help you practice the following skills:
Interrogating online databases of human genomic variation
Interpreting evidence of genomic variant functional effects
Summarising and reporting on genomic information
This assignment will help you gain the following knowledge:
Understanding the structure and organisation of genes, chromosomes, and the human genome.
Understanding how genomic variant information is represented
Familiarity with the levels of evidence used to determine variant pathogenicity
Task
A patient has undergone whole-genome sequencing to assist their clinical team in the diagnosis of a rare disease. A large number of variants were discovered in the patients genome. These variants now must be interpreted to determine their clinical significance.
You have each been assigned four genomic variants found in the patient.
The details of the variants that you have been allocated are available on the Canvas page for this assignment.
For each variant, perform each of the activities (1-4) below and answer all the listed questions. Video tutorials are available on the Canvas site to assist you.
Upon completion of the activities and answering the questions for each variant, prepare a single report summarising what you have found and your conclusions.
The report must contain the following sections:
BackgroundNo more than 250 words.
Include:
purpose of the investigation;the variants being investigated;information on the genes the variants you were assigned are located in, their molecular function, and the diseases that occur when this function is interrupted; and
a summary of the methods and tools used.
FindingsYour findings should include answers to the questions listed under Activities 1-4, written in text. Please include detailed figures and table legends and describe your findings in complete sentences. The size of figures and tables should be at least half an A4 page.
Conclusion
Include a conclusion that summarises your findings and explains their significance in terms of how likely it is that the variants you have been assigned are causative of disease, and the quality of the evidence used to determine the significance. This section should not be longer than 250 words.
References
Use the Vancouver reference system with numbering throughout the report. Be sure to cite all sources of information that you have used in compiling your report.
The main body of the report should be no longer than 5 pages. Additional diagrams or outputs from websites can be added as appendices if required but must not exceed 4 additional pages.
An electronic Word file of your report must be submitted through Canvas. Details will be provided on the Canvas site.
Activity 1: Identify the gene(s) the variants occur in and their structures
Search v.3.1.2 of gnomAD (Genome Aggregation Database; https://gnomad.broadinstitute.org/) using the genomic coordinates of each variant that you have been assigned. Identify the gene(s) these coordinates occur in and navigate to the gnomAD page for each gene.
Questions:
How many transcripts (splice variants) does each gene have?
What is the accession number of the highest quality transcript?
Determine the number of exons and introns in the best quality gene transcript.
Provide a diagram showing the structural arrangement of exons and introns in the highest quality transcript.
Activity 2: Investigate the function of the gene(s)
Search the OMIM database (Online Mendelian Inheritance in Man; https://www.omim.org/) for each of the genes you have identified. Use the information contained in OMIM and the provided links to other information sources to learn more about the function of the genes and any medical conditions that they have been linked to.
Questions:
What are the common tissues in which the genes are expressed?
What is known about the molecular function of the genes?
What medical conditions do these genes play a role in?
Activity 3: Investigate the assigned variants
Return to gnomAD and search for your assigned variants.
Questions:
Are your assigned variants present in the v.3.1.2 gnomAD dataset?
If yes:
How many times does this variant occur in the gnomAD dataset?
What is the quality of the information in the gnomAD dataset at this locus?
Which area of the gene are the variants located? (exon, intron, etc).
Do they change the coding region?
What potential effect, if any, on the final protein has been predicted or observed?
Has any determination been made about the clinical significance of these variants?
How confident can you be in these determinations?
If no:
What can you infer from the fact that the variant is not present in the v.3.1.2 gnomAD dataset?
Activity 4: Investigate other variants within the gene(s)
Questions:
What is the total number of variants present in the v.3.1.2 gnomAD dataset for these gene(s)?
What is the total number of variants present in the ClinGen dataset for these gene(s)?
Have any of these variants been classified as pathogenic or likely pathogenic? If yes, what evidence exists to support this?
Criteria for Success
As Medical Scientists we must strive for specificity and accuracy. Reports such as the one that you are being asked to produce often form the basis of decisions about healthcare options for patients. Therefore, it is extremely important that you state your findings clearly and accurately and detail the evidence that you have used to draw your conclusions. All evidence must be appropriately referenced, including information taken from online databases.
The provided rubric for this assignment should be used as a guide to assist you in writing your report.
Rubric
Criteria Ratings Points
Background 25 to >20.0 Pts
High Distinction (80% - 100%)
An excellent and comprehensive overview of the literature and information from listed websites using a critical approach. Thoroughly discusses the use of bioinformatics tools or the roles of genes studied in health and disease. 20to >17.5Pts
Distinction (70% - 79%)
Provides a very strong overview of the literature and information from listed websites with a critical approach. Executes a thorough discussion of the use of bioinformatics tools or the roles of genes studied in health and disease reflecting a high level of understanding.
17.5to >15.0Pts
Credit (60% - 69%)
Delivers a solid overview of the literature and information from listed websites, demonstrating a good critical approach. Provides a sound discussion of the use of bioinformatics tools or the roles of genes studied in health and disease, indicating a competent level of understanding.
15to >12.5Pts
Pass (50% - 59%)
Delivered an acceptable overview of the literature and information from listed websites, with some evidence of a critical approach. Presents a satisfactory discussion of the use of bioinformatics tools or genes studied in health and disease, meeting the basic requirements.
12.5 to >0 Pts
Fail (0% - 49%)
Does not provide an adequate overview. Significant gaps in knowledge are evident. Lacks information on the use of bioinformatics tools or genes studied, indicating a failure to meet the minimum requirements. 25
Findings 50 to >40.0 Pts
High Distinction (80% - 100%)
Clearly explains all results for the four activities with excellent organisation of information. Excellent presentation of figures and/or tables and were half an A4 page in size. Describes titles and legends for figures and/or tables with exceptional clarity. 40.0 to >35. Pts
Distinction (70% - 79%)
Explains some results are clearly with good organisation of information. Presents figures and/or tables well, with most were half an A4 page in size. Describes title and legends for figures and/or tables are mostly well. 35.0 to >30.0 Pts
Credit (60% - 69%)
Explains most results adequately with satisfactory organisation of information. Presents figures and/or tables in a good manner, with many being half an A4 page in size. Describes title and legends for figures and/or tables competently. 30.0 to >25.0 Pts
Pass (50% - 59%)
Explains some results with acceptable organisation of information. Presents figures and/or tables adequately, with some being half an A4 page in size. Describes titles and legends for figures and/or tables meeting the basic requirements. 25.0 to >0 Pts
Fail (0% - 49%)
Superficially explains all results, making them difficult to understand. Demonstrates unsatisfactory organisation of information. Fails to present figures/tables or presents poorly constructed ones. Lacks figure/table titles or legends, indicating a failure to meet the minimum requirements. 50
Conclusion 18 to >14.4 Pts
High Distinction (80% - 100%)
Clearly summarizes the key findings concerning the studied variants. Provides an excellent and detailed explanation of the significance and quality of these findings in the context of molecular genetics and diagnostics in disease. 14.4 to >12.6 Pts
Distinction (70% - 79%)
Includes a good summary of key findings and attempts to highlight the significance and quality of these findings in the context of molecular genetics and diagnostics in disease. 12.6 to >10.8 Pts
Credit (60% 69%)
Attempts a fair summary of key findings but falls short of highlighting the significance or quality of these findings in the context of molecular genetics and diagnostics in disease. 10.8 to >9.0 Pts
Pass (50% - 59%)
Attempts a summary of key findings, but the explanation of their significance or quality is not thorough or clear in the context of molecular genetics and diagnostics in disease. 9.0 to >0 Pts
Fail (0% - 49%)
A clear conclusion is not apparent. Fails to provide a summary of key findings and an explanation of their significance or quality in the context of molecular genetics and diagnostics in disease. 18
Referencing 7.0 to >5.6 Pts
High Distinction (80% - 100%)
Cites all references (including databases) correctly in the text, and references in the Bibliography are complete using the Vancouver style with exceptional accuracy. 5.6 to >4.9 Pts
Distinction (70% - 79%)
Cites all references (including databases) correctly in the text. Incomplete references are found in the Bibliography, but overall, it uses the Vancouver style effectively. 4.9 to >4.2 Pts
Credit (60% 69%)
Cites some references wrongly in the text with incomplete references in the Bibliography. Utilises the Vancouver style, but there are areas for improvement. 4.2 to >3.5 Pts
Pass (50% - 59%)
Majority of references are cited correctly in the text, but some are incomplete. Bibliography contains incomplete references. Uses the Vancouver style but with notable room for improvement. 3.5 to >0 Pts
Fail (0% - 49%)
The majority of references are wrongly cited, missing, or incomplete in the text. Uses other referencing styles apart from the Vancouver style, indicating a failure to meet the minimum requirements. 7
100 pt
