Modularization of biochemical networks based on classification of Petri net t-invariants

<p>Abstract</p> <p>Background</p> <p>Structural analysis of biochemical networks is a growing field in bioinformatics and systems biology. The availability of an increasing amount of biological data from molecular biological networks promises a deeper understanding but confronts researchers with the problem of combinatorial explosion. The amount of qualitative network data is growing much faster than the amount of quantitative data, such as enzyme kinetics. In many cases it is even impossible to measure quantitative data because of limitations of experimental methods, or for ethical reasons. Thus, a huge amount of qualitative data, such as interaction data, is available, but it was not sufficiently used for modeling purposes, until now. New approaches have been developed, but the complexity of data often limits the application of many of the methods. Biochemical Petri nets make it possible to explore static and dynamic qualitative system properties. One Petri net approach is model validation based on the computation of the system's invariant properties, focusing on t-invariants. T-invariants correspond to subnetworks, which describe the basic system behavior.</p> <p>With increasing system complexity, the basic behavior can only be expressed by a huge number of t-invariants. According to our validation criteria for biochemical Petri nets, the necessary verification of the biological meaning, by interpreting each subnetwork (t-invariant) manually, is not possible anymore. Thus, an automated, biologically meaningful classification would be helpful in analyzing t-invariants, and supporting the understanding of the basic behavior of the considered biological system.</p> <p>Methods</p> <p>Here, we introduce a new approach to automatically classify t-invariants to cope with network complexity. We apply clustering techniques such as UPGMA, Complete Linkage, Single Linkage, and Neighbor Joining in combination with different distance measures to get biologically meaningful clusters (t-clusters), which can be interpreted as modules. To find the optimal number of t-clusters to consider for interpretation, the cluster validity measure, Silhouette Width, is applied.</p> <p>Results</p> <p>We considered two different case studies as examples: a small signal transduction pathway (pheromone response pathway in <it>Saccharomyces cerevisiae</it>) and a medium-sized gene regulatory network (gene regulation of Duchenne muscular dystrophy). We automatically classified the t-invariants into functionally distinct t-clusters, which could be interpreted biologically as functional modules in the network. We found differences in the suitability of the various distance measures as well as the clustering methods. In terms of a biologically meaningful classification of t-invariants, the best results are obtained using the Tanimoto distance measure. Considering clustering methods, the obtained results suggest that UPGMA and Complete Linkage are suitable for clustering t-invariants with respect to the biological interpretability.</p> <p>Conclusion</p> <p>We propose a new approach for the biological classification of Petri net t-invariants based on cluster analysis. Due to the biologically meaningful data reduction and structuring of network processes, large sets of t-invariants can be evaluated, allowing for model validation of qualitative biochemical Petri nets. This approach can also be applied to elementary mode analysis.</p

Measurement of the Spin Asymmetry in the Photoproduction of Pairs of High-pT Hadrons at HERMES

We present a measurement of the longitudinal spin asymmetry A_|| in photoproduction of pairs of hadrons with high transverse momentum p_T. Data were accumulated by the HERMES experiment using a 27.5 GeV polarized positron beam and a polarized hydrogen target internal to the HERA storage ring. For h+h- pairs with p_T^h_1 > 1.5 GeV/c and p_T^h_2 > 1.0 GeV/c, the measured asymmetry is A_|| = -0.28 +/- 0.12 (stat.) +/- 0.02 (syst.). This negative value is in contrast to the positive asymmetries typically measured in deep inelastic scattering from protons, and is interpreted to arise from a positive gluon polarization.Comment: 5 pages (latex), 4 figures (eps

Measurement of the Proton Spin Structure Function g1p with a Pure Hydrogen Target

A measurement of the proton spin structure function g1p(x,Q^2) in deep-inelastic scattering is presented. The data were taken with the 27.6 GeV longitudinally polarised positron beam at HERA incident on a longitudinally polarised pure hydrogen gas target internal to the storage ring. The kinematic range is 0.021<x<0.85 and 0.8 GeV^2<Q^2<20 GeV^2. The integral Int_{0.021}^{0.85} g1p(x)dx evaluated at Q0^2 of 2.5 GeV^2 is 0.122+/-0.003(stat.)+/-0.010(syst.).Comment: 7 pages, 3 figures, 1 table, RevTeX late

Beam-Induced Nuclear Depolarisation in a Gaseous Polarised Hydrogen Target

Spin-polarised atomic hydrogen is used as a gaseous polarised proton target in high energy and nuclear physics experiments operating with internal beams in storage rings. When such beams are intense and bunched, this type of target can be depolarised by a resonant interaction with the transient magnetic field generated by the beam bunches. This effect has been studied with the HERA positron beam in the HERMES experiment at DESY. Resonances have been observed and a simple analytic model has been used to explain their shape and position. Operating conditions for the experiment have been found where there is no significant target depolarisation due to this effect.Comment: REVTEX, 6 pages, 5 figure

Determination of the Deep Inelastic Contribution to the Generalised Gerasimov-Drell-Hearn Integral for the Proton and Neutron

The virtual photon absorption cross section differences [sigma_1/2-sigma_3/2] for the proton and neutron have been determined from measurements of polarised cross section asymmetries in deep inelastic scattering of 27.5 GeV longitudinally polarised positrons from polarised 1H and 3He internal gas targets. The data were collected in the region above the nucleon resonances in the kinematic range nu < 23.5 GeV and 0.8 GeV**2 < Q**2 < 12 GeV**2. For the proton the contribution to the generalised Gerasimov-Drell-Hearn integral was found to be substantial and must be included for an accurate determination of the full integral. Furthermore the data are consistent with a QCD next-to-leading order fit based on previous deep inelastic scattering data. Therefore higher twist effects do not appear significant.Comment: 6 pages, 3 figures, 1 table, revte

The Flavor Asymmetry of the Light Quark Sea from Semi-inclusive Deep-inelastic Scattering

The flavor asymmetry of the light quark sea of the nucleon is determined in the kinematic range 0.02<x<0.3 and 1 GeV^2<Q^2<10 GeV^2, for the first time from semi-inclusive deep-inelastic scattering. The quantity (dbar(x)-ubar(x))/(u(x)-d(x)) is derived from a relationship between the yields of positive and negative pions from unpolarized hydrogen and deuterium targets. The flavor asymmetry dbar-ubar is found to be non-zero and x dependent, showing an excess of dbar over ubar quarks in the proton.Comment: 7 Pages, 2 figures, RevTeX format; slight revision in text, small change in extraction of dbar-ubar and comparison with a high q2 parameterizatio

Exclusive Leptoproduction of rho^0 Mesons from Hydrogen at Intermediate Virtual Photon Energies

Measurements of the cross section for exclusive virtual-photoproduction of rho^0 mesons from hydrogen are reported. The data were collected by the HERMES experiment using 27.5 GeV positrons incident on a hydrogen gas target in the HERA storage ring. The invariant mass W of the photon-nucleon system ranges from 4.0 to 6.0 GeV, while the negative squared four-momentum Q^2 of the virtual photon varies from 0.7 to 5.0 GeV^2. The present data together with most of the previous data at W > 4 GeV are well described by a model that infers the W-dependence of the cross section from the dependence on the Bjorken scaling variable x of the unpolarized structure function for deep-inelastic scattering. In addition, a model calculation based on Off-Forward Parton Distributions gives a fairly good account of the longitudinal component of the rho^0 production cross section for Q^2 > 2 GeV^2.Comment: 10 pages, 6 embedded figures, LaTeX for SVJour(epj) document class. Revisions: curves added to Fig. 1, several clarifications added to tex

Observation of a Coherence Length Effect in Exclusive Rho^0 Electroproduction

Exclusive incoherent electroproduction of the rho^0(770) meson from 1H, 2H, 3He, and 14N targets has been studied by the HERMES experiment at squared four-momentum transfer Q**2>0.4 GeV**2 and positron energy loss nu from 9 to 20 GeV. The ratio of the 14N to 1H cross sections per nucleon, known as the nuclear transparency, was found to decrease with increasing coherence length of quark-antiquark fluctuations of the virtual photon. The data provide clear evidence of the interaction of the quark- antiquark fluctuations with the nuclear medium.Comment: RevTeX, 5 pages, 3 figure

Double-Spin Asymmetry in the Cross Section for Exclusive rho^0 Production in Lepton-Proton Scattering

Evidence for a positive longitudinal double-spin asymmetry = 0.24 +-0.11 (stat) +-0.02 (syst) in the cross section for exclusive diffractive rho^0(770) vector meson production in polarised lepton-proton scattering was observed by the HERMES experiment. The longitudinally polarised 27.56 GeV HERA positron beam was scattered off a longitudinally polarised pure hydrogen gas target. The average invariant mass of the photon-proton system has a value of = 4.9 GeV, while the average negative squared four-momentum of the virtual photon is = 1.7 GeV^2. The ratio of the present result to the corresponding spin asymmetry in inclusive deep-inelastic scattering is in agreement with an early theoretical prediction based on the generalised vector meson dominance model.Comment: 10 pages, 4 embedded figures, LaTe

Measurement of Longitudinal Spin Transfer to Lambda Hyperons in Deep-Inelastic Lepton Scattering

Spin transfer in deep-inelastic Lambda electroproduction has been studied with the HERMES detector using the 27.6 GeV polarized positron beam in the HERA storage ring. For an average fractional energy transfer = 0.45, the longitudinal spin transfer from the virtual photon to the Lambda has been extracted. The spin transfer along the Lambda momentum direction is found to be 0.11 +/- 0.17 (stat) +/- 0.03 (sys); similar values are found for other possible choices for the longitudinal spin direction of the Lambda. This result is the most precise value obtained to date from deep-inelastic scattering with charged lepton beams, and is sensitive to polarized up quark fragmentation to hyperon states. The experimental result is found to be in general agreement with various models of the Lambda spin content, and is consistent with the assumption of helicity conservation in the fragmentation process.Comment: 8 pages, 3 figures; new version has an expanded discussion and small format change