Evaluation of network-guided random forest for disease gene discovery

Gene network information is believed to be beneficial for disease module and pathway identification, but has not been explicitly utilized in the standard random forest (RF) algorithm for gene expression data analysis. We investigate the performance of a network-guided RF where the network information is summarized into a sampling probability of predictor variables which is further used in the construction of the RF. Our results suggest that network-guided RF does not provide better disease prediction than the standard RF. In terms of disease gene discovery, if disease genes form module(s), network-guided RF identifies them more accurately. In addition, when disease status is independent from genes in the given network, spurious gene selection results can occur when using network information, especially on hub genes. Our empirical analysis on two balanced microarray and RNA-Seq breast cancer datasets from The Cancer Genome Atlas (TCGA) for classification of progesterone receptor (PR) status also demonstrates that network-guided RF can identify genes from PGR-related pathways, which leads to a better connected module of identified genes.Comment: 23 pages, 2 tables, 7 figure

A review on longitudinal data analysis with random forest in precision medicine

Precision medicine provides customized treatments to patients based on their characteristics and is a promising approach to improving treatment efficiency. Large scale omics data are useful for patient characterization, but often their measurements change over time, leading to longitudinal data. Random forest is one of the state-of-the-art machine learning methods for building prediction models, and can play a crucial role in precision medicine. In this paper, we review extensions of the standard random forest method for the purpose of longitudinal data analysis. Extension methods are categorized according to the data structures for which they are designed. We consider both univariate and multivariate responses and further categorize the repeated measurements according to whether the time effect is relevant. Information of available software implementations of the reviewed extensions is also given. We conclude with discussions on the limitations of our review and some future research directions.Comment: 27 pages, 2 figures, 3 table

Efficient Construction for Full Black-Box Accountable Authority Identity-Based Encryption

Accountable authority identity-based encryption (A-IBE), as an attractive way to guarantee the user privacy security, enables a malicious private key generator (PKG) to be traced if it generates and re-distributes a user private key. Particularly, an A-IBE scheme achieves full black-box security if it can further trace a decoder box and is secure against a malicious PKG who can access the user decryption results. In PKC\u2711, Sahai and Seyalioglu presented a generic construction for full black-box A-IBE from a primitive called dummy identity-based encryption, which is a hybrid between IBE and attribute-based encryption (ABE). However, as the complexity of ABE, their construction is inefficient and the size of private keys and ciphertexts in their instantiation is linear in the length of user identity. In this paper, we present a new efficient generic construction for full black-box A-IBE from a new primitive called token-based identity-based encryption (TB-IBE), without using ABE. We first formalize the definition and security model for TB-IBE. Subsequently, we show that a TB-IBE scheme satisfying some properties can be converted to a full black-box A-IBE scheme, which is as efficient as the underlying TB-IBE scheme in terms of computational complexity and parameter sizes. Finally, we give an instantiation with the computational complexity as O(1) and the constant size master key pair, private keys, and ciphertexts

All-optical spatio-temporal metrology for isolated attosecond pulses

Characterizing an isolated attosecond pulse (IAP) is essential for its potential applications. A complete characterization of an IAP ultimately requires the determination of its electric field in both time and space domains. However, previous methods, like the widely-used RABBITT and attosecond streaking, only measure the temporal profile of the attosecond pulse. Here we demonstrate an all-optical method for the measurement of the space-time properties of an IAP. By introducing a non-collinear perturbing pulse to the driving field, the process of IAP generation is modified both spatially and temporally, manifesting as a spatial and a frequency modulation in the harmonic spectrum. By using a FROG-like retrieval method, the spatio-spectral phases of the harmonic spectrum are faithfully extracted from the induced spatio-spectral modulations, which allows a thoroughgoing characterization of the IAP in both time and space. With this method, the spatio-temporal structures of the IAP generated in a two-color driving field in both the near- and far-field are fully reconstructed, from which a weak spatio-temporal coupling in the IAP generation is revealed. Our approach overcomes the limitation in the temporal measurement in conventional in situ scheme, providing a reliable and holistic metrology for IAP characterization.Comment: 18 pages, 5 figure

Functional evaluation of cyclosporine metabolism by CYP3A4 variants and potential drug interactions

The aim of this study is to investigate the effects of CYP3A4 genetic polymorphisms on the metabolism of cyclosporine (CsA) in vitro and identify drugs that interact with CsA. An enzymatic incubation system was developed to evaluate the kinetic parameters of CYP3A4 on CsA catalysis. A total of 132 drugs were screened to identify potential drug–drug interactions. Sprague–Dawley rats were used to determine the interaction between CsA and nimodipine and nisoldipine. The metabolite AM1 was measured by ultra-performance liquid chromatography–tandem mass spectrometry. The results demonstrate that 16 CYP3A4 variants (CYP3A4.7, 8, 9, 12, 13, 14, 16, 18, 19, 23, 24, 28, 31, 32, 33, and 34) have a lower metabolic capacity for CsA, ranging from 7.19% to 72.10%, than CYP3A4.1. In contrast, the relative clearance rate of CYP3A4.5 is significantly higher than that of CYP3A4.1. Moreover, CYP3A4.20 loses its catalytic ability, and five other variants have no significant difference. A total of 12 drugs, especially calcium channel blockers, were found to remarkably inhibit the metabolism of CsA with an inhibitory rate of over 80%. Nimodipine inhibits the activity of CsA in rat liver microsomes with an IC50 of 20.54 ± 0.93 μM, while nisoldipine has an IC50 of 16.16 ± 0.78 μM. In in vivo, three groups of Sprague–Dawley rats were administered CsA with or without nimodipine or nisoldipine; the AUC(0-t) and AUC(0-∞) of CsA were significantly increased in the nimodipine group but not obviously in the nisoldipine group. Mechanistically, the inhibition mode of nimodipine on cyclosporine metabolism is a mixed inhibition. Our data show that gene polymorphisms of CYP3A4 and nimodipine remarkably affect the metabolism of CsA, thus providing a reference for the precise administration of CsA

Simultaneous determination of cortisone and cortisol in serum by HPLC-DAD and application for pharmacokinetics

To develop a high performance liquid chromatography method for the simultaneous determination of cortisone and cortisol in rat serum and apply it for pharmacokinetics. After addition of pirfenidone as internal standard (IS), a liquid-liquid extraction with ethylacetate was employed for the sample preparation. Samples were separated on Zorbax SB-C18 column at 25 ºC using mobile phase consisting of acetonitrile-water-0.1 % trifluoroacetic acid with flow rate of 0.9 mL/min, utilizing DAD detection at 246 nm. Excellent liner relationships of the cortisone and cortisol concentrations were obtained from 50 to 6000 ng/mL, with r = 0.9997, 0.9999 respectively, and the lower limit of quantitation (LLOQ) were both 50 ng/mL. The developed method was successfully applied to pharmacokinetic studies of cortisone and cortisol in rats following single dose of 20 mg/kg via intraperitoneal injection.Colegio de Farmacéuticos de la Provincia de Buenos Aire

Integrated System Built for Small-Molecule Semiconductors via High-Throughput Approaches

High-throughput synthesis of solution-processable structurally variable small-molecule semiconductors is both an opportunity and a challenge. A large number of diverse molecules provide a possibility for quick material discovery and machine learning based on experimental data. However, the diversity of molecular structure leads to the complexity of molecular properties, such as solubility, polarity, and crystallinity, which poses great challenges to solution processing and purification. Here, we first report an integrated system for the high-throughput synthesis, purification, and characterization of molecules with a large variety. Based on the principle of Like dissolves like, we combine theoretical calculations and a robotic platform to accelerate the purification of those molecules. With this platform, a material library containing 125 molecules and their optical-electric properties was built within a timeframe of weeks. More importantly, the high repeatability of recrystallization we design is a reliable approach to further upgrading and industrial production

Integrated System Built for Small-Molecule Semiconductors via High-Throughput Approaches

High-throughput synthesis of solution-processable structurally variable small-molecule semiconductors is both an opportunity and a challenge. A large number of diverse molecules provide a possibility for quick material discovery and machine learning based on experimental data. However, the diversity of the molecular structure leads to the complexity of molecular properties, such as solubility, polarity, and crystallinity, which poses great challenges to solution processing and purification. Here, we first report an integrated system for the high-throughput synthesis, purification, and characterization of molecules with a large variety. Based on the principle “Like dissolves like,” we combine theoretical calculations and a robotic platform to accelerate the purification of those molecules. With this platform, a material library containing 125 molecules and their optical-electronic properties was built within a timeframe of weeks. More importantly, the high repeatability of recrystallization we design is a reliable approach to further upgrading and industrial production

Evaluation of network-guided random forest for disease gene discovery

Abstract Background Gene network information is believed to be beneficial for disease module and pathway identification, but has not been explicitly utilized in the standard random forest (RF) algorithm for gene expression data analysis. We investigate the performance of a network-guided RF where the network information is summarized into a sampling probability of predictor variables which is further used in the construction of the RF. Results Our simulation results suggest that network-guided RF does not provide better disease prediction than the standard RF. In terms of disease gene discovery, if disease genes form module(s), network-guided RF identifies them more accurately. In addition, when disease status is independent from genes in the given network, spurious gene selection results can occur when using network information, especially on hub genes. Our empirical analysis on two balanced microarray and RNA-Seq breast cancer datasets from The Cancer Genome Atlas (TCGA) for classification of progesterone receptor (PR) status also demonstrates that network-guided RF can identify genes from PGR-related pathways, which leads to a better connected module of identified genes. Conclusions Gene networks can provide additional information to aid the gene expression analysis for disease module and pathway identification. But they need to be used with caution and validation on the results need to be carried out to guard against spurious gene selection. More robust approaches to incorporate such information into RF construction also warrant further study