Differential gene and transcript expression analysis of RNA-seq experiments with TopHat and Cufflinks

Recent advances in high-throughput cDNA sequencing (RNA-seq) can reveal new genes and splice variants and quantify expression genome-wide in a single assay. The volume and complexity of data from RNA-seq experiments necessitate scalable, fast and mathematically principled analysis software. TopHat and Cufflinks are free, open-source software tools for gene discovery and comprehensive expression analysis of high-throughput mRNA sequencing (RNA-seq) data. Together, they allow biologists to identify new genes and new splice variants of known ones, as well as compare gene and transcript expression under two or more conditions. This protocol describes in detail how to use TopHat and Cufflinks to perform such analyses. It also covers several accessory tools and utilities that aid in managing data, including CummeRbund, a tool for visualizing RNA-seq analysis results. Although the procedure assumes basic informatics skills, these tools assume little to no background with RNA-seq analysis and are meant for novices and experts alike. The protocol begins with raw sequencing reads and produces a transcriptome assembly, lists of differentially expressed and regulated genes and transcripts, and publication-quality visualizations of analysis results. The protocol's execution time depends on the volume of transcriptome sequencing data and available computing resources but takes less than 1 d of computer time for typical experiments and ~1 h of hands-on time

Applications of the leading-order Dokshitzer-Gribov-Lipatov-Altarelli-Parisi evolution equations to the combined HERA data on deep inelastic scattering

We recently derived explicit solutions of the leading-order Dokshitzer-Gribov-Lipatov-Altarelli-Parisi (DGLAP) equations for the $Q^2$ evolution of the singlet structure function $F_s(x,Q^2)$ and the gluon distribution $G(x,Q^2)$ using very efficient Laplace transform techniques. We apply our results here to a study of the HERA data on deep inelastic $ep$ scattering as recently combined by the H1 and ZEUS groups. We use initial distributions $F_2^{\gamma p}(x,Q_0^2)$ and $G(x,Q_0^2)$ fixed by a global fit to the HERA data. From $F_2^{\gamma p}(x,Q_0^2)$ we obtain the singlet quark distribution $F_s(x,Q_0^2)$---using small non-singlet quark distributions taken from either the CTEQ6L or the MSTW2008LO analyses---evolve to arbitrary $Q^2$, and then convert the results to individual quark distributions. Finally, we show directly from a study of systematic trends in a comparison of the evolved $F_2^{\gamma p}(x,Q^2)$ with the HERA data, that the assumption of leading-order DGLAP evolution is inconsistent with those data.Comment: 18 pages, 7 figures, version accepted for publication in PR

Effective field theory and the quark model

We analyze the connections between the quark model (QM) and the description of hadrons in the low-momentum limit of heavy-baryon effective field theory in QCD. By using a three-flavor-index representation for the effective baryon fields, we show that the ``nonrelativistic'' constituent QM for baryon masses and moments is completely equivalent through O(m_s) to a parametrization of the relativistic field theory in a general spin--flavor basis. The flavor and spin variables can be identified with those of effective valence quarks. Conversely, the spin-flavor description clarifies the structure and dynamical interpretation of the chiral expansion in effective field theory, and provides a direct connection between the field theory and the semirelativistic models for hadrons used in successful dynamical calculations. This allows dynamical information to be incorporated directly into the chiral expansion. We find, for example, that the striking success of the additive QM for baryon magnetic moments is a consequence of the relative smallness of the non-additive spin-dependent corrections.Comment: 25 pages, revtex, no figure

Perturbative reliability of the Higgs-boson coupling in the standard electroweak model

We apply Pade summation to the \beta(\lambda) function for the quartic Higgs coupling \lambda in the standard electroweak model. We use the \beta function calculated to five loops in the minimal subtraction scheme to demonstrate the improvement resulting from the summation, and then apply the method to the more physical on-mass-shell renormalization scheme where \beta is known to three loops. We conclude that the OMS \beta function and the running coupling \lambda(\mu) are reliably known over the range of energies and Higgs-boson masses of current interest.Comment: 14 pages, RevTeX, 6 figure

Baryon Magnetic Moments in a QCD-based Quark Model with loop corrections

We study meson loop corrections to the baryon magnetic moments starting from a QCD-based quark model derived earlier in a quenched approximation to QCD. The model reproduces the standard quark model with extra corrections for the binding of the quarks. The loop corrections are necessary to remove the quenching. Our calculations use heavy baryon perturbation theory with chiral baryon-meson couplings and a form factor characterizing the structure of baryons as composite particles. The form factor reflects soft wave function effects with characteristic momenta $\approx 400$ MeV, well below the usual chiral cutoff of $\approx 1$ GeV. The resulting model involves only three parameters, the quark moments $\mu_u$ and $\mu_s$ and a parameter $\lambda$ that sets the momentum scale in the wavefunctions. We find that this approach substantially improves the agreement between the theoretical and experimental values of the octet baryon magnetic moments, with an average difference between the theoretical and experimental moments of 0.05$\mu_N$. An extension to the decuplet states using the same input predicts a moment of 1.97 $\mu_N$ for the $\Omega^-$ hyperon, in excellent agreement with the measured moment of $2.02\pm0.05 \mu_N$.Comment: 23 pages, 3 figure

Spatiotemporal expression and transcriptional perturbations by long noncoding RNAs in the mouse brain

Long noncoding RNAs (lncRNAs) have been implicated in numerous cellular processes including brain development. However, the in vivo expression dynamics and molecular pathways regulated by these loci are not well understood. Here, we leveraged a cohort of 13 lncRNA-null mutant mouse models to investigate the spatiotemporal expression of lncRNAs in the developing and adult brain and the transcriptome alterations resulting from the loss of these lncRNA loci. We show that several lncRNAs are differentially expressed both in time and space, with some presenting highly restricted expression in only selected brain regions. We further demonstrate altered regulation of genes for a large variety of cellular pathways and processes upon deletion of the lncRNA loci. Finally, we found that 4 of the 13 lncRNAs significantly affect the expression of several neighboring protein-coding genes in a cis-like manner. By providing insight into the endogenous expression patterns and the transcriptional perturbations caused by deletion of the lncRNA locus in the developing and postnatal mammalian brain, these data provide a resource to facilitate future examination of the specific functional relevance of these genes in neural development, brain function, and disease.National Science Foundation (U.S.) (Postdoctoral Research Fellowship in Biology DBI-0905973

New Particles Working Group Report of the Snowmass 2013 Community Summer Study

This report summarizes the work of the Energy Frontier New Physics working group of the 2013 Community Summer Study (Snowmass)