Summary Cancer can be classified into various subtypes by its molecular, histological or clinical characteristics. Discovering cancer-subtype-specific drugs is a crucial step in personalized medicine. SubtypeDrug is a system biology R-based software package that enables the prioritization of subtype-specific drugs based on cancer expression data from samples of many subtypes. This provides a novel approach to identify the subtype-specific drug by considering biological functions regulated by drugs at the subpathway level. The operation modes include extraction of subpathways from biological pathways, identification of dysregulated subpathways induced by each drug, inference of sample-specific subpathway activity profiles, evaluation of drug-disease reverse association at the subpathways level, identification of cancer-subtype-specific drugs through subtype sample set enrichment analysis, and visualization of the results. Its capabilities enable SubtypeDrug to find subtype-specific drugs, which will fill the gaps in the recent tools which only identify the drugs for a particular cancer type. SubtypeDrug may help to facilitate the development of tailored treatment for patients with cancer. Availability and implementation The package is implemented in R and available under GPL-2 license from the CRAN website (https://CRAN.R-project.org/package=SubtypeDrug). Supplementary information Supplementary data are available at Bioinformatics online.
We present direct numerical simulations of the spatial development of normal mode perturbations to boundary layers with Falkner–Skan velocity profiles. Values of the pressure gradient parameter considered range from very small, i.e. nearly flat-plate conditions, to relatively large values corresponding to incipient separation. In almost all cases, we find that the most effective perturbation is one composed of a plane wave and a pair of oblique waves inclined at equal and opposite angles to the primary flow direction. The frequency of the oblique waves is half that of the fundamental plane wave and because the conditions for resonance are satisfied exactly, all modes share a common critical layer, thus facilitating a strong interaction.The oblique waves initially undergo a parametric type of subharmonic resonance, but in accordance with recent analyses of non-equilibrium critical layers, the system subsequently becomes fully coupled. From that point on, the amplification of all modes, including the plane wave, substantially exceeds the predictions of linear stability theory. Good agreement is obtained with the experimental small pressure gradient results of Corke & Gruber (1996). Our growth rates are slightly larger flowing to slight differences in initial conditions (e.g. the angle of inclination of the oblique waves).The spectral element method was used to discretize the Navier–Stokes equations and the preconditioned conjugate gradient method was used to solve the resulting system of algebraic equations. At the inflow boundary, Orr–Sommerfeld modes were employed to provide the initial forcing, whereas the buffer domain technique was used at the outflow boundary to prevent convective wave reflection or upstream propagation of spurious information.
The nonlinear critical layer theory is developed for the case where the critical point is close enough to a solid boundary so that the critical layer and viscous wall layers merge. It is found that the flow structure differs considerably from the symmetric "cat's eye" pattern obtained by Benney and Bergeron [1] and Haberman [2]. One of the new features is that higher harmonics generated by the critical layer are in some cases induced in the outer flow at the same order as the basic disturbance. As a consequence, the lowest-order critical layer problem must be solved numerically. In the inviscid limit, on the other hand, a closedform solution is obtained. It has continuous vorticity and is compared with the solutions found by Bergeron [3], which contain discontinuities in vorticity across closed streamlines.
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