We have applied our algorithm to the clinical and genomic data from breast cancer patients treated with neoadjuvant chemotherapy in a recent prospective clinical study and have identified the most promising druggable targets and pathways that are activated. From these data, the PANOPLY system identifies the most promising drug targets. Specifically, PANOPLY takes pre-processed data such as germline DNA sequence, somatic single nucleotide variants (SNVs), small insertions and deletions (INDELs), copy number variants (CNVs), fusion transcripts, along with RNA seq gene expression data to build an integrated network which ranks the cancer genesets for a given patient. The objective of PANOPLY is to process a variety of “omics” data along with molecular, pathological and clinical data from cancer patients with the ultimate goal of “individualizing therapy. This approach is used to summarize knowledge into informative and predictive models to narrow appropriate treatment options and to aid clinician/researchers in decision making. We have developed PANOPLY a novel computational approach to integrate both germline and somatic data obtained from multi-omics platforms for an individual of interest and analyze that data in the context matched-control samples. Overview of the PANOPLY system: With the advent of high throughput technologies, the quantity of ‘omics’ data has rapidly increased, creating the need for methodologies that can analyze complex datasets and provide interpretations that assist in decision making. This catalogue suggests that rheumatological manifestations and immune dysregulation are relatively common in GATA2 deficiency.PANOPLY- Precision C ancer Ge nomic Re port: Single Samp le Inventor y Further, PPP and joint hyperextensibility may explain some of the nonimmunologically-mediated joint problems encountered in patients with GATA2 deficiency. Low total helper T lymphocyte proportions and low naïve helper T cell proportions are associated with those most at risk of overt rheumatological manifestations.
Conclusion: GATA2 deficiency is associated with a broad spectrum of rheumatological disease manifestations. No changes in CD19, CD3, or NK populations were observed. In peripheral blood of patients with rheumatological manifestations and GATA2 deficiency, CD4+ CD3+ helper T cells and naïve CD3+ CD4+ CD62L+ CD45RA+ helper T cell subpopulation fractions were significantly lower, while CD8+ cytotoxic T cell fractions were significantly higher, compared to those without rheumatological manifestations and with GATA2 deficiency. Notable rheumatological manifestations included: piezogenic pedal papules (PPP), joint hyperextensibility, early onset osteoarthritis, ankylosing spondylitis, and seronegative erosive rheumatoid arthritis. Twenty-two of those patients (78.6%) reported symptom onset prior to or in conjunction with the molecular diagnosis of GATA2 deficiency. Results: Rheumatological findings were identified in 28 patients, out of 157 cases reviewed (17.8%). A literature search of four databases was conducted to identify additional cases. In-person rheumatological assessments were performed on selected, available patients.
Disease course, laboratory results, and imaging findings were extracted. Methods: Single-center, retrospective review of 157 patients with GATA2 deficiency. Purpose: To characterize rheumatological manifestations of GATA2 deficiency.
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