BackgroundNeuroblastoma is a heterogeneous disease with diverse clinical outcomes. Current risk group models require improvement as patients within the same risk group can still show variable prognosis. Recently collected genome-wide datasets provide opportunities to infer neuroblastoma subtypes in a more unified way. Within this context, data integration is critical as different molecular characteristics can contain complementary signals. To this end, we utilized the genomic datasets available for the SEQC cohort patients to develop supervised and unsupervised models that can predict disease prognosis.ResultsOur supervised model trained on the SEQC cohort can accurately predict overall survival and event-free survival profiles of patients in two independent cohorts. We also performed extensive experiments to assess the prediction accuracy of high risk patients and patients without MYCN amplification. Our results from this part suggest that clinical endpoints can be predicted accurately across multiple cohorts. To explore the data in an unsupervised manner, we used an integrative clustering strategy named multi-view kernel k-means (MVKKM) that can effectively integrate multiple high-dimensional datasets with varying weights. We observed that integrating different gene expression datasets results in a better patient stratification compared to using these datasets individually. Also, our identified subgroups provide a better Cox regression model fit compared to the existing risk group definitions.ConclusionAltogether, our results indicate that integration of multiple genomic characterizations enables the discovery of subtypes that improve over existing definitions of risk groups. Effective prediction of survival times will have a direct impact on choosing the right therapies for patients.ReviewersThis article was reviewed by Susmita Datta, Wenzhong Xiao and Ziv Shkedy.Electronic supplementary materialThe online version of this article (10.1186/s13062-018-0223-8) contains supplementary material, which is available to authorized users.

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Abstract:We demonstrate continuous-wave (cw), cw frequency-doubled, cw mode-locked and Q-switched mode-locked operation of multimode diode-pumped Cr:LiCAF lasers with record average powers. Up to 2.54 W of cw output is obtained around 805 nm at an absorbed pump power of 5.5 W. Using intracavity frequency doubling with a BBO crystal, 0.9 W are generated around 402 nm, corresponding to an optical-to-optical conversion efficiency of 12%. With an intracavity birefringent tuning plate, the fundamental and frequency-doubled laser output is tuned continuously in a broad wavelength range from 745 nm to 885 nm and from 375 to 440 nm, respectively. A saturable Bragg reflector is used to initiate and sustain mode locking. In the cw mode-locked regime, the Cr:LiCAF laser produces 105-fs long pulses near 810 nm with an average power of 0.75 W. The repetition rate is 96.4 MHz, resulting in pulse energies of 7.7 nJ and peak powers of 65 kW. In Q-switched mode-locked operation, pulses with energies above 150 nJ are generated.

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