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Angelina Elizabeth Uno-Antonison
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# Reanalysis and Reinterpretation of Exome and Genome Data
[TOC]
Reanalysis of previously sequenced exomes and genomes is a standard approach for clinical sequencing laboratories.
The power from reanalysis comes from multiple activities within the field, changes in analytical pipelines and changes
in clinical status of the patients/participants within the clinical sites. An additional diagnostic rate of 11% has
been published obtained three-to-four years after an initial report and 5% after a two-year interval from the original
report date. These results support the value of instituting reinterpretation and reanalysis for rare disease cases
that remain without a diagnosis. Reanalysis may also be helpful for those cases in which one diagnosis may not
completely explain the observed phenotype (e.g., J. Posey, Resolution of disease phenotypes resulting from multilocus
genomic variation, New Engl J Med 376:21-31, 2017).
## Approach
There are two different analytic approaches proposed: reanalysis and reinterpretation.
### Reanalysis
> Definition: Start with raw data and rerun the entire analysis and interpretation. Recommend conducting with a
significant pipeline change or at specific time intervals. Upon reanalysis, an amended report will be issued which
communicates results, new findings, or no changes to original interpretation.
### Reinterpretation
> Definition: Review of variants in the context of new data in the literature, both new disease gene associations
and changes in variant interpretation. Reinterpretation should be conducted annually. Amended reports will be issued
indicating new interpretations, new diagnoses, or no new revised findings.
## Components
| Component | Details |
|----------|:-------------|
| Re-review clinical records | Extract new clinical information and review by director |
| Re-review existing data files | Re-review genomic information for completeness & quality |
| Secondary reanalysis FastQ through VCF | Reprocessing through bioinformatics pipeline |
| Tertiary analysis VCF through prioritization | Reprocessing to obtain primary review file |
| Interpretation (analyst review) | Initial analysis and subsequent discussions |
| Interpretation (director review) | Initial analysis and subsequent discussions |
| Report generation and approval | Reviewing/compiling report |
| Return of findings | Review and preparation of final packet |