Knowledge-based variable selection for learning rules from proteomic data

<p>Abstract</p> <p>Background</p> <p>The incorporation of biological knowledge can enhance the analysis of biomedical data. We present a novel method that uses a proteomic knowledge base to enhance the performance of a rule-learning algorithm in identifying putative biomarkers of disease from high-dimensional proteomic mass spectral data. In particular, we use the Empirical Proteomics Ontology Knowledge Base (EPO-KB) that contains previously identified and validated proteomic biomarkers to select <it>m/z</it>s in a proteomic dataset prior to analysis to increase performance.</p> <p>Results</p> <p>We show that using EPO-KB as a pre-processing method, specifically selecting all biomarkers found only in the biofluid of the proteomic dataset, reduces the dimensionality by 95% and provides a statistically significantly greater increase in performance over no variable selection and random variable selection.</p> <p>Conclusion</p> <p>Knowledge-based variable selection even with a sparsely-populated resource such as the EPO-KB increases overall performance of rule-learning for disease classification from high-dimensional proteomic mass spectra.</p

Exclusive Lambda_b -> Lambda l^+ l^- decay in two Higgs doublet model

Rare Lambda_b -> Lambda l^+ l^- decay is investigated in framework of general two Higgs doublet model, in which a new source of CP violation exists (model III). The polarization parameter, CP asymmetry and decay width are calculated. It is shown that CP asymmetry is a very sensitive tool for establishing model III.Comment: 16 pages, 3 figures, LaTeX formatte

Enhancing the top signal at Tevatron using Neural Nets

We show that Neural Nets can be useful for top analysis at Tevatron. The main features of $t\bar t$ and background events on a mixed sample are projected in a single output, which controls the efficiency and purity of the $t\bar t$ signal.Comment: 11 pages, 6 figures (not included and available from the authors), Latex, UB-ECM-PF 94/1

Medicines adherence: Involving patients in decisions about prescribed medicines and supporting adherence

It is thought that between a third and a half of all medicines1 There are many causes of non-adherence but they fall into two overlapping categories: intentional and unintentional. Unintentional non-adherence occurs when the patient wants to follow the agreed treatment but is prevented from doing so by barriers that are beyond their control. Examples include poor recall or difficulties in understanding the instructions, problems with using the treatment, inability to pay for the treatment, or simply forgetting to take it. prescribed for long-term conditions are not taken as recommended. If the prescription is appropriate, then this may represent a loss to patients, the healthcare system and society. The costs are both personal and economic. Adherence presumes an agreement between prescriber and patient about the prescriber’s recommendations. Adherence to medicines is defined as the extent to which the patient’s action matches the agreed recommendations. Non-adherence may limit the benefits of medicines, resulting in lack of improvement, or deterioration, in health. The economic costs are not limited to wasted medicines but also include the knock-on costs arising from increased demands for healthcare if health deteriorates. Non-adherence should not be seen as the patient’s problem. It represents a fundamental limitation in the delivery of healthcare, often because of a failure to fully agree the prescription in the first place or to identify and provide the support that patients need later on. Addressing non-adherence is not about getting patients to take more medicines per se. Rather, it starts with an exploration of patients’ perspectives of medicines and the reasons why they may not want or are unable to use them. Healthcare professionals have a duty to help patients make informed decisions about treatment and use appropriately prescribed medicines to best effec

The Neutron Electric Dipole Moment and CP-violating Couplings in the Supersymmetric Standard Model without R-parity

We analyze the neutron electric dipole moment (EDM) in the Minimal Supersymmetric Model with explicit R-parity violating terms. The leading contribution to the EDM occurs at the 2-loop level and is dominated by the chromoelectric dipole moments of quarks, assuming there is no tree-level mixings between sleptons and Higgs bosons or between leptons and gauginos. Based on the experimental constraint on the neutron EDM, we set limits on the imaginary parts of complex couplings ${\lambda'}_{ijk}$ and ${\lambda}_{ijk}$ due to the virtual b-loop or tau-loop.Comment: final manuscript to appear in Phys. Rev. D, 15 pages, latex, 4 figures include

Detection of the heavy Higgs boson at γγ\gamma\gamma colliders

We consider the possibility of detecting a heavy Higgs boson ($m_H>2m_Z$) in proposed $\gamma\gamma$ colliders through the semi-leptonic mode $\gamma\gamma \rightarrow H \rightarrow ZZ \rightarrow q\bar q \ell^+\ell^-$. We show that due to the non-monochromatic nature of the photon beams produced by the laser-backscattering method, the resultant cross section for Higgs production is much smaller than the on-resonance cross section and generally {\it decreases} with increasing collider energy. Although continuum $ZZ$ production is expected to be negligible, we demonstrate the presence of and calculate sizeable backgrounds from $\gamma\gamma\rightarrow \ell^+\ell^-Z,\,q\bar qZ$, with $Z\rightarrow q\bar q,\,\ell^+\ell^-$, respectively, and $\gamma\gamma\rightarrow t\bar t\rightarrow b\bar b\ell^+\ell^-\nu\bar\nu$. This channel may be used to detect a Higgs of mass $m_H$ up to around 350~GeV at a 0.5~TeV $e^+e^-$ collider, assuming a nominal yearly luminosity of 10--20~fb$^{-1}$.Comment: 18 pages (in RevTeX) plus Postscript figures (available by email or FAX), NUHEP-TH-92-29 and DOE-309-CPP-47. (Revised version: NO CHANGES to the manuscript, simply removed corrupted figure files

Proteomics and mathematical modeling of longitudinal CSF differentiates fast versus slow ALS progression

Objective: Amyotrophic lateral sclerosis (ALS) is a heterogeneous disease with a complex etiology that lacks biomarkers predicting disease progression. The objective of this study was to use longitudinal cerebrospinal fluid (CSF) samples to identify biomarkers that distinguish fast progression (FP) from slow progression (SP) and assess their temporal response.Methods: We utilized mass spectrometry (MS)-based proteomics to identify candidate biomarkers using longitudinal CSF from a discovery cohort of SP and FP ALS patients. Immunoassays were used to quantify and validate levels of the top biomarkers. A state-transition mathematical model was created using the longitudinal MS data that also predicted FP versus SP.Results: We identified a total of 1148 proteins in the CSF of all ALS patients. Pathway analysis determined enrichment of pathways related to complement and coagulation cascades in FPs and synaptogenesis and glucose metabolism in SPs. Longitudinal analysis revealed a panel of 59 candidate markers that could segregate FP and SP ALS. Based on multivariate analysis, we identified three biomarkers (F12, RBP4, and SERPINA4) as top candidates that segregate ALS based on rate of disease progression. These proteins were validated in the discovery and a separate validation cohort. Our state-transition model determined that the overall variance of the proteome over time was predictive of the disease progression rate.Interpretation: We identified pathways and protein biomarkers that distinguish rate of ALS disease progression. A mathematical model of the CSF proteome determined that the change in entropy of the proteome over time was predictive of FP versus SP

The CP asymmetry for B--> K^* l^+ l^- decay in the general two Higgs doublet model

We study CP asymmetry for the exclusive decay B --> K^* l^+ l^- in the two Higgs doublet model with three level flavor changing neutral currents (model III). We analyse the dependency of this quantity to the new phase coming from the complex Yukawa couplings in the theory and we find that there exist a considerable CP violation for the relevant process. Further, we see that the sign of the Wilson coefficient C_7^{eff} can be determined by fixing dilepton mass. Therefore, the future measurements of CP asymmetry for B --> K^* l^+ l^- decay will give a powerful information about the sign of Wilson coefficient C_{7}^{eff} and the new physics beyond the SM.Comment: 22 pages, 8 figure

Aspects of Soft and Spontaneous CP Violation

We study four different models for CP violation: the standard (KM) model, the aspon model of spontaneous breaking and two models of soft breaking. In all except the standard model, the strong CP problem is addressed and solved. Testable predictions for the area of the unitarity triangle and for (epsilon'/epsilon)_K are emphasized. The issue of CP violation may well become the first place where the standard model of particle theory is shown definitively to be deficient. There are two reasons for expecting this to happen: (1) the strong CP problem is still not understood in the unadorned standard model and (2) the KM mechanism, although unquestionably present, may not provide the full explanation of epsilon_K and (epsilon'/epsilon)_K.Comment: 24 pages LaTeX including 4 figures. Minor modification to analysis of lower bound for d_n, summarized in new Table I