SeqReporter The Journal of Molecular Diagnostics

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SeqReporter The Journal of Molecular Diagnostics Somak Roy, Mary Beth Durso, Abigail Wald, Yuri E. Nikiforov, Marina N. Nikiforova The Journal of Molecular Diagnostics Volume 16, Issue 1, Pages 11-22 (January 2014) DOI: 10.1016/j.jmoldx.2013.08.005 Copyright © 2014 American Society for Investigative Pathology and the Association for Molecular Pathology Terms and Conditions

Figure 1 Typical NGS testing workflow in a clinical laboratory. The Journal of Molecular Diagnostics 2014 16, 11-22DOI: (10.1016/j.jmoldx.2013.08.005) Copyright © 2014 American Society for Investigative Pathology and the Association for Molecular Pathology Terms and Conditions

Figure 2 SeqReporter annotation and classification algorithm. The flow diagram illustrates the information flow starting from import of variant calls, coverage information, sample and run information, followed by annotation (levels 1 and 2) and classification. See the Results section for details. DB, database; INDEL, insertion and deletion. The Journal of Molecular Diagnostics 2014 16, 11-22DOI: (10.1016/j.jmoldx.2013.08.005) Copyright © 2014 American Society for Investigative Pathology and the Association for Molecular Pathology Terms and Conditions

Figure 3 SeqReporter variant review and knowledge base training algorithm. The SIRM extracts the case details and the variant call management module (VMM) and the report synthesis module (RSM) present a preliminary but detailed report of all of the variant calls of the sample in an interactive HTML format when a pathologist receives the case for sign-out. The report (Supplemental Figure S1) enables the pathologist to make any changes and reclassify the variants if necessary. When all of the changes are made and the report is signed-off, the changes are saved to the sample information database. Simultaneously, the knowledge base training module is initiated, which iterates through every single data field of all variants to scan for changes. If any changes are detected, the appropriate data field(s) in the appropriate data table is modified, therefore enriching the knowledge base with the most updated information. DB, database; SRIM, sample and run information module. The Journal of Molecular Diagnostics 2014 16, 11-22DOI: (10.1016/j.jmoldx.2013.08.005) Copyright © 2014 American Society for Investigative Pathology and the Association for Molecular Pathology Terms and Conditions

Figure 4 Algorithm underlying report synthesis module. Per a request from the pathologist’s workstation, the report synthesis module extracts user-defined relevant fields from the database to populate the report. The actual data are converted from a SQL data table to a generic XML schema, which is available for conversion to one of the three desired formats (OpenXML, PDF, or HTML). The Journal of Molecular Diagnostics 2014 16, 11-22DOI: (10.1016/j.jmoldx.2013.08.005) Copyright © 2014 American Society for Investigative Pathology and the Association for Molecular Pathology Terms and Conditions

Figure 5 Results of successful variant classification by SeqReporter. A and B: Number of variants across genes on the AmpliSeq hotspot version 1 panel and tumor type, respectively. The Journal of Molecular Diagnostics 2014 16, 11-22DOI: (10.1016/j.jmoldx.2013.08.005) Copyright © 2014 American Society for Investigative Pathology and the Association for Molecular Pathology Terms and Conditions

Figure 6 Histogram showing the trend in efficiency of SeqReporter’s variant classification algorithm. A statistically significant improvement in variant classification was noted as more cases were analyzed and reviewed in SeqReporter. The three sets of 10 consecutive cases represent subsets of the 58 cases after validation across different time points (z-test, GraphPad Prism version 6.0c). The Journal of Molecular Diagnostics 2014 16, 11-22DOI: (10.1016/j.jmoldx.2013.08.005) Copyright © 2014 American Society for Investigative Pathology and the Association for Molecular Pathology Terms and Conditions