SuperFreq: Integrated mutation detection and clonal tracking in cancer.

Analysing multiple cancer samples from an individual patient can provide insight into the way the disease evolves. Monitoring the expansion and contraction of distinct clones helps to reveal the mutations that initiate the disease and those that drive progression. Existing approaches for clonal tracking from sequencing data typically require the user to combine multiple tools that are not purpose-built for this task. Furthermore, most methods require a matched normal (non-tumour) sample, which limits the scope of application. We developed SuperFreq, a cancer exome sequencing analysis pipeline that integrates identification of somatic single nucleotide variants (SNVs) and copy number alterations (CNAs) and clonal tracking for both. SuperFreq does not require a matched normal and instead relies on unrelated controls. When analysing multiple samples from a single patient, SuperFreq cross checks variant calls to improve clonal tracking, which helps to separate somatic from germline variants, and to resolve overlapping CNA calls. To demonstrate our software we analysed 304 cancer-normal exome samples across 33 cancer types in The Cancer Genome Atlas (TCGA) and evaluated the quality of the SNV and CNA calls. We simulated clonal evolution through in silico mixing of cancer and normal samples in known proportion. We found that SuperFreq identified 93% of clones with a cellular fraction of at least 50% and mutations were assigned to the correct clone with high recall and precision. In addition, SuperFreq maintained a similar level of performance for most aspects of the analysis when run without a matched normal. SuperFreq is highly versatile and can be applied in many different experimental settings for the analysis of exomes and other capture libraries. We demonstrate an application of SuperFreq to leukaemia patients with diagnosis and relapse samples

Fluctuations, Saturation, and Diffractive Excitation in High Energy Collisions

Diffractive excitation is usually described by the Good--Walker formalism for low masses, and by the triple-Regge formalism for high masses. In the Good--Walker formalism the cross section is determined by the fluctuations in the interaction. In this paper we show that by taking the fluctuations in the BFKL ladder into account, it is possible to describe both low and high mass excitation by the Good--Walker mechanism. In high energy $pp$ collisions the fluctuations are strongly suppressed by saturation, which implies that pomeron exchange does not factorise between DIS and $pp$ collisions. The Dipole Cascade Model reproduces the expected triple-Regge form for the bare pomeron, and the triple-pomeron coupling is estimated.Comment: 20 pages, 12 figure

Extracting the Distribution Amplitudes of the rho meson from the Color Glass Condensate

We extract the leading twist-2 and subleading twist-3 Distribution Amplitudes (DAs) of the rho meson using the HERA data on diffractive rho photoproduction. We do so using several Colour Glass Condensate (CGC) inspired and a Regge inspired dipole models. We find that our extracted twist-2 DA is not much model dependent and is consistent with QCD Sum Rules and lattice predictions. The extracted twist-3 DA is more model dependent but is still consistent with the Sum Rules prediction.Comment: 21 pages, 10 figures, 3 tables. Section 6 revised, figures 8 and 9 and table 3 updated. Conclusions essentially unchange

Elastic and quasi-elastic pppp and γ⋆p\gamma^\star p scattering in the Dipole Model

We have in earlier papers presented an extension of Mueller's dipole cascade model, which includes sub-leading effects from energy conservation and running coupling as well as colour suppressed saturation effects from pomeron loops via a ``dipole swing''. The model was applied to describe the total and diffractive cross sections in $pp$ and $\gamma^*p$ collisions, and also the elastic cross section in $pp$ scattering. In this paper we extend the model to describe the corresponding quasi-elastic cross sections in $\gamma^*p$, namely the exclusive production of vector mesons and deeply virtual compton scattering. Also for these reactions we find a good agrement with measured cross sections. In addition we obtain a reasonable description of the $t$-dependence of the elastic $pp$ and quasi-elastic $\gamma^\star p$ cross sections

Confining strings in SU(N) gauge theories

We calculate the string tensions of $k$-strings in SU($N$) gauge theories in both 3 and 4 dimensions. In D=3+1, we find that the ratio of the $k=2$ string tension to the $k = 1$ fundamental string tension is consistent, at the $2 \sigma$ level, with both the M(-theory)QCD-inspired conjecture and with `Casimir scaling'. In D=2+1 we see a definite deviation from the MQCD formula, as well as a much smaller but still significant deviation from Casimir scaling. We find that in both D=2+1 and D=3+1 the high temperature spatial $k$-string tensions also satisfy approximate Casimir scaling. We point out that approximate Casimir scaling arises naturally if the cross-section of the flux tube is nearly independent of the flux carried, and that this will occur in an effective dual superconducting description, if we are in the deep-London limit. We estimate, numerically, the intrinsic width of $k$-strings in D=2+1 and indeed find little variation with $k$. In addition to the stable $k$-strings we investigate some ofthe unstable strings, finding in D=2+1 that they satisfy (approximate) Casimir scaling. We also investigate the basic assumption that confining flux tubes are described by an effective string theory at large distances. We estimate the coefficient of the universal L\"uscher correction from periodic strings that are longer than 1 fermi, and find $c_L=0.98(4)$ in D=3+1 and $c_L=0.558(19)$ in D=2+1. These values are within $2 \sigma$ of the simple bosonic string values and are inconsistent with other simple effective string theories.Comment: 57 pages, 11 figures. Errors on fits reduced by altering the analysis to a standard one. Conclusions unchanged; note addedchanged. Some typos correcte

Lattice calculation of 1−+1^{-+} hybrid mesons with improved Kogut-Susskind fermions

We report on a lattice determination of the mass of the exotic $1^{-+}$ hybrid meson using an improved Kogut-Susskind action. Results from both quenched and dynamical quark simulations are presented. We also compare with earlier results using Wilson quarks at heavier quark masses. The results on lattices with three flavors of dynamical quarks show effects of sea quarks on the hybrid propagators which probably result from coupling to two meson states. We extrapolate the quenched results to the physical light quark mass to allow comparison with experimental candidates for the $1^{-+}$ hybrid meson. The lattice result remains somewhat heavier than the experimental result, although it may be consistent with the $\pi_1(1600)$.Comment: 24 pages, 12 figures. Replaced to match published versio

Hybrid and Conventional Mesons in the Flux Tube Model: Numerical Studies and their Phenomenological Implications

We present results from analytical and numerical studies of a flux tube model of hybrid mesons. Our numerical results use a Hamiltonian Monte Carlo algorithm and so improve on previous analytical treatments, which assumed small flux tube oscillations and an adiabatic separation of quark and flux tube motion. We find that the small oscillation approximation is inappropriate for typical hadrons and that the hybrid mass is underestimated by the adiabatic approximation. For physical parameters in the ``one-bead" flux tube model we estimate the lightest hybrid masses (${}_\Lambda L = {}_1 P$ states) to be 1.8-1.9~GeV for $u\bar u$ hybrids, 2.1-2.2~GeV for $s\bar s$ and 4.1-4.2~GeV for $c\bar c$. We also determine masses of conventional $q\bar q$ mesons with $L=0$ to $L=3$ in this model, and confirm good agreement with experimental $J$-averaged multiplet masses. Mass estimates are also given for hybrids with higher orbital and flux-tube excitations. The gap from the lightest hybrid level (${}_1P$) to the first hybrid orbital excitation (${}_1D$) is predicted to be $\approx 0.4$~GeV for light quarks $(q=u,d)$ and $\approx 0.3$~GeV for $q=c$. Both ${}_1P$ and ${}_1D$ hybrid multiplets contain the exotics $1^{-+}$ and $2^{+-}$; in addition the ${}_1P$ has a $0^{+-}$ and the ${}_1D$ contains a $3^{-+}$. Hybrid mesons with doubly-excited flux tubes are also considered. The implications of our results for spectroscopy are discussed, with emphasis on charmonium hybrids, which may be accessible at facilities such as BEPC, KEK, a Tau-Charm Factory, and in $\psi$ production at hadron colliders.Comment: 39 pages of RevTex. Figures available via anonymous ftp at ftp://compsci.cas.vanderbilt.edu/QSM/bcsfig1.ps and /QSM/bcsfig6.p

Coulomb gauge approach to (qqg)over-bar hybrid mesons

An effective Coulomb gauge Hamiltonian, H-eff, is used to calculate the light ( u (u) over barg), strange ( s (s) over barg) and charmed (c (c) over barg) hybrid meson spectra. For the same two parameter H-eff providing glueball masses consistent with lattice results and a good description of the observed u, d, s and c quark mesons, a large-scale variational treatment predicts that the lightest hybrid has J(PC) = 0(++) and mass 2.1 GeV. The lightest exotic 1(-+) state is just above 2.2 GeV, near the upper limit of lattice and flux tube predictions. These theoretical formulations all indicate that the observed 1(-+) pi(1)(1600) and, more clearly, pi(1)(1400) are not hybrid states. The Coulomb gauge approach further predicts that in the strange and charmed sectors, respectively, the ground state hybrids have 1(+-) with masses 2.1 and 3.8 GeV, while the. rst exotic 1( +) states are at 2.4 and 4.0 GeV. Finally, using our hybrid wavefunctions and the Franck-Condon principle, a novel experimental signature is presented to assist heavy hybrid meson searches