RESULTS: We developed DeSigN, a web-based tool for predicting drug efficacy against cancer cell lines using gene expression patterns. The algorithm correlates phenotype-specific gene signatures derived from differentially expressed genes with pre-defined gene expression profiles associated with drug response data (IC50) from 140 drugs. DeSigN successfully predicted the right drug sensitivity outcome in four published GEO studies. Additionally, it predicted bosutinib, a Src/Abl kinase inhibitor, as a sensitive inhibitor for oral squamous cell carcinoma (OSCC) cell lines. In vitro validation of bosutinib in OSCC cell lines demonstrated that indeed, these cell lines were sensitive to bosutinib with IC50 of 0.8-1.2 μM. As further confirmation, we demonstrated experimentally that bosutinib has anti-proliferative activity in OSCC cell lines, demonstrating that DeSigN was able to robustly predict drug that could be beneficial for tumour control.
CONCLUSIONS: DeSigN is a robust method that is useful for the identification of candidate drugs using an input gene signature obtained from gene expression analysis. This user-friendly platform could be used to identify drugs with unanticipated efficacy against cancer cell lines of interest, and therefore could be used for the repurposing of drugs, thus improving the efficiency of drug development.
METHODS: Children having home overnight oximetry for suspected OSA were identified over 12 months, and those with a normal result who went on to have polysomnography (PSG) were included. Oximetry, including PR-SD and PRI (rises of 8, 10 and 15 beats/min per hour), was analyzed using commercially available software. PR parameters were compared between those with OSA (obstructive apnoea-hypopnoea index (OAHI) >1 event/h) and those without OSA.
RESULTS: One hundred sixteen children had normal oximetry, of whom 93 (median age 4.5 years; 55 % M) had PSG. Fifty-seven of 93 (61 %) children had OSA (median OAHI 4.5 events/h, range 1.1-24). PR-SD was not different between the OSA and non-OSA groups (p = 0.87). PRI tended to be higher in those with OSA, but there was considerable overlap between the groups: PRI-8 (mean ± SD 58.5 ± 29.0/h in OSA group vs 48.6 ± 20.2/h in non-OSA group, p = 0.07), PRI-10 (45.1 ± 25.0 vs 36.2 ± 16.7, p = 0.06) and PRI-15 (24.4 ± 14.5 vs 18.9 ± 9.0, p = 0.04). A PRI-15 threshold of >35/h had specificity of 97 % for OSA.
CONCLUSION: The PRI-15 shows promise as an indicator of OSA in children with normal oximetry.