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| Identifier |
000425729 |
| Title |
An open and interactive pipeline for variant analysis and downstream exome sequencing analysis |
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Author
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Αστρινάκη, Μαρία
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Thesis advisor
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Ποταμιάς, Γεώργιος
Καφετζόπουλος, Δημήτριος
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| Abstract |
Next Generation Sequencing (NGS) is a technique for the profiling of the DNA sequence of an
organism that has been constantly developed and optimized over the last 20 years. Today, the
quality, automation and cost-effectiveness of this technique has reached a level that can be
directly applied in diagnostic and therapeutic protocols of modern health-care systems. A typical
NGS pipeline starts with sample preparation and concludes with a report that is delivered to the
clinician. This report contains all findings, usually genetic mutations, with important
implications and clinical relevance to the condition of the patient. Two of the most important
intermediate steps of this procedure is the annotation and prioritization of the identified
mutations. Annotation is the process of complementing a list of mutations with information
available in existing and open genetic databases. Prioritization is the process of applying various
criteria to the variants in order to rank them according to their pathogenicity. Usually the variants
reported to the clinicians are the ones that have the highest rankings. Although all steps of the
NGS pipeline have been thoroughly standardized for a wide set of sequencing platforms and
diagnostic scenaria, prioritization remains on of the most subjective and under-standardized step.
As of today, the most known systematization process for variant prioritization is the set of
guidelines introduced by the American College of Medical Genetics and Genomics (ACMG).
However, these guidelines are far from complete and contain many vague directions that are
open to interpretation by clinical geneticists. The subjective interpretation of these guidelines
combined with the plethora of annotation information for tens of thousands of mutations, creates
a bewildered terrain for the researcher. To alleviate this, we create an environment, call Zazz
which serves two purposes. The first is to store in a relational database the variants and the
annotation information of a set of samples. The second is to offer a query and exploration
environment where users can apply and fine-tune the prioritization guidelines. Zazz offers a
simple User Interface through which the user can apply complex queries and also offers an
interactive exploration envirοnment that visualizes variants through modern javascript graph
toolkits. Zazz is also integrated with a graphic genome browser. We demonstrate the efficiency
of Zazz with exome sequencing data annotated with the IonReporter suite and the open
annotation tools VEP and ANNOVAR. We also show how Zazz can accommodate custom
annotation fields by importing data from a custom parser of the ClinVar database which extracts
fields that other annotation platforms omit. Overall Zazz is a platform that helps clinical
geneticists to browse a huge amount of information with the purpose of creating concise reports,
in a timely manner
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| Language |
English |
| Subject |
Exomes |
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Next generation sequensing |
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Variant priorizitation open software |
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Αλληλούχιση επόμενης γενιάς |
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Εξώματα |
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Ταξινόμηση παραλλαγών ανοιχτού λογισμικού |
| Issue date |
2019-12-11 |
| Collection
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School/Department--School of Medicine--Department of Medicine--Post-graduate theses
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Type of Work--Post-graduate theses
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| Views |
420 |
An open and interactive pipeline for variant analysis and downstream exome sequencing analysis
