MCMC-ODPR : primer design optimization using Markov Chain Monte Carlo sampling

Background Next generation sequencing technologies often require numerous primer designs that require good target coverage that can be financially costly. We aimed to develop a system that would implement primer reuse to design degenerate primers that could be designed around SNPs, thus find the fewest necessary primers and the lowest cost whilst maintaining an acceptable coverage and provide a cost effective solution. We have implemented Metropolis-Hastings Markov Chain Monte Carlo for optimizing primer reuse. We call it the Markov Chain Monte Carlo Optimized Degenerate Primer Reuse (MCMC-ODPR) algorithm. Results After repeating the program 1020 times to assess the variance, an average of 17.14% fewer primers were found to be necessary using MCMC-ODPR for an equivalent coverage without implementing primer reuse. The algorithm was able to reuse primers up to five times. We compared MCMC-ODPR with single sequence primer design programs Primer3 and Primer-BLAST and achieved a lower primer cost per amplicon base covered of 0.21 and 0.19 and 0.18 primer nucleotides on three separate gene sequences, respectively. With multiple sequences, MCMC-ODPR achieved a lower cost per base covered of 0.19 than programs BatchPrimer3 and PAMPS, which achieved 0.25 and 0.64 primer nucleotides, respectively. Conclusions MCMC-ODPR is a useful tool for designing primers at various melting temperatures at good target coverage. By combining degeneracy with optimal primer reuse the user may increase coverage of sequences amplified by the designed primers at significantly lower costs. Our analyses showed that overall MCMC-ODPR outperformed the other primer-design programs in our study in terms of cost per covered base

Archaeogenetic evidence of ancient Nubian barley evolution from six to two-row indicates local adaptation

Background Archaeobotanical samples of barley (Hordeum vulgare L.) found at Qasr Ibrim display a two-row phenotype that is unique to the region of archaeological sites upriver of the first cataract of the Nile, characterised by the development of distinctive lateral bracts. The phenotype occurs throughout all strata at Qasr Ibrim, which range in age from 3000 to a few hundred years. Methodology and Findings We extracted ancient DNA from barley samples from the entire range of occupancy of the site, and studied the Vrs1 gene responsible for row number in extant barley. Surprisingly, we found a discord between the genotype and phenotype in all samples; all the barley had a genotype consistent with the six-row condition. These results indicate a six-row ancestry for the Qasr Ibrim barley, followed by a reassertion of the two-row condition. Modelling demonstrates that this sequence of evolutionary events requires a strong selection pressure. Conclusions The two-row phenotype at Qasr Ibrim is caused by a different mechanism to that in extant barley. The strength of selection required for this mechanism to prevail indicates that the barley became locally adapted in the region in response to a local selection pressure. The consistency of the genotype/phenotype discord over time supports a scenario of adoption of this barley type by successive cultures, rather than the importation of new barley varieties associated with individual cultures

Domestication as innovation : the entanglement of techniques, technology and chance in the domestication of cereal crops

The origins of agriculture involved pathways of domestication in which human behaviours and plant genetic adaptations were entangled. These changes resulted in consequences that were unintended at the start of the process. This paper highlights some of the key innovations in human behaviours, such as soil preparation, harvesting and threshing, and how these were coupled with genetic ‘innovations’ within plant populations. We identify a number of ‘traps’ for early cultivators, including the needs for extra labour expenditure on crop-processing and soil fertility maintenance, but also linked gains in terms of potential crop yields. Compilations of quantitative data across a few different crops for the traits of nonshattering and seed size are discussed in terms of the apparently slow process of domestication, and parallels and differences between different regional pathways are identified. We highlight the need to bridge the gap between a Neolithic archaeobotanical focus on domestication and a focus of later periods on crop-processing activities and labour organization. In addition, archaeobotanical data provide a basis for rethinking previous assumptions about how plant genetic data should be related to the origins of agriculture and we contrast two alternative hypotheses: gradual evolution with low selection pressure versus metastable equilibrium that prolonged the persistence of ‘semi-domesticated’ populations. Our revised understanding of the innovations involved in plant domestication highlight the need for new approaches to collecting, modelling and integrating genetic data and archaeobotanical evidence

Elastic pp-scattering at \sqrt s=7 TeV with the genuine Orear regime and the dip

The unitarity condition unambigously requires the Orear region to appear in between the diffraction cone at low transferred momenta and hard parton scattering regime at high transferred momenta in hadron elastic scattering. It originates from rescattering of the diffraction cone processes. It is shown that such region has been observed in the differential cross section of the elastic pp-scattering at \sqrt s=7 TeV. The Orear region is described by exponential decrease with the scattering angle and imposed on it damped oscillations. They explain the steepening at the end of the diffraction cone as well as the dip and the subsequent maximum observed in TOTEM data. The failure of several models to describe the data in this region can be understood as improper account of the unitarity condition. It is shown that the real part of the amplitude can be as large as the imaginary part in this region. The overlap function is calculated and shown to be small outside the diffraction peak. Its negative sign there indicates the important role of phases in the amplitudes of inelastic processes.Comment: 5 pages, 2 figures, revtex

Global QCD Analysis and the CTEQ Parton Distributions

The CTEQ program for the determination of parton distributions through a global QCD analysis of data for various hard scattering processes is fully described. A new set of distributions, CTEQ3, incorporating several new types of data is reported and compared to the two previous sets of CTEQ distributions. Comparison with current data is discussed in some detail. The remaining uncertainties in the parton distributions and methods to further reduce them are assessed. Comparisons with the results of other global analyses are also presented.Comment: (Change in Latex style only: 2up style removed since many don't have it.) 35 pages, 23 figures separately submitted as uuencoded compressed ps-file; Michigan State Report # MSU-HEP/41024 and CTEQ 40

Simulations from a new neutrino event generator

We construct a new Monte Carlo generator of events for neutrino interactions. The dynamical models for quasi-elastic reactions, $\Delta$ excitation and more inelastic events described by the DIS formalism with the PDFs modified according to recent JLab data are used. We describe in detail single pion production channels, which combine the $\Delta$ excitation and DIS contribution. Many comparisons of the outcome of simulations with experimental data are presented.Comment: To appear in the proceedings of 4th International Workshop on Neutrino Nucleus Interactions in the Few GeV Region (NuInt05), Okayama, Japan, 26-29 September, 200

A Precise Measurement of the Weak Mixing Angle in Neutrino-Nucleon Scattering

We report a precise measurement of the weak mixing angle from the ratio of neutral current to charged current inclusive cross-sections in deep-inelastic neutrino-nucleon scattering. The data were gathered at the CCFR neutrino detector in the Fermilab quadrupole-triplet neutrino beam, with neutrino energies up to 600 GeV. Using the on-shell definition, ${\rm sin ^2\theta_W} \equiv 1 - \frac{{\rm M_W} ^2}{{\rm M_Z} ^2}$, we obtain ${\rm sin ^2\theta_W} = 0.2218 \pm 0.0025 ({\rm stat.}) \pm 0.0036 ({\rm exp.\: syst.}) \pm 0.0040 ({\rm model})$.Comment: 10 pages, Nevis Preprint #1498 (Submitted to Phys. Rev. Lett.

Leptoproduction of Heavy Quarks II -- A Unified QCD Formulation of Charged and Neutral Current Processes from Fixed-target to Collider Energies

A unified QCD formulation of leptoproduction of massive quarks in charged current and neutral current processes is described. This involves adopting consistent factorization and renormalization schemes which encompass both vector-boson-gluon-fusion (flavor creation) and vector-boson-massive-quark-scattering (flavor excitation) production mechanisms. It provides a framework which is valid from the threshold for producing the massive quark (where gluon-fusion is dominant) to the very high energy regime when the typical energy scale \mu is much larger than the quark mass m_Q (where the quark-scattering should be prevalent). This approach effectively resums all large logarithms of the type (alpha_s(mu) log(mu^2/m_Q^2)^n which limit the validity of existing fixed-order calculations to the region mu ~ O(m_Q). We show that the (massive) quark-scattering contribution (after subtraction of overlaps) is important in most parts of the (x, Q) plane except near the threshold region. We demonstrate that the factorization scale dependence of the structure functions calculated in this approach is substantially less than those obtained in the fixed-order calculations, as one would expect from a more consistent formulation.Comment: LaTeX format, 29 pages, 11 figures. Revised to make auto-TeX-abl

Neutrino Interactions In Oscillation Experiments

We calculate neutrino induced cross-sections relevant for oscillation experiments, including the $\tau$-lepton threshold for quasi-elastic, resonance and deep inelastic scattering. In addition to threshold effects, we include nuclear corrections for heavy targets which are moderate for quasi-elastic and large for single pion production. Nuclear effects for deep inelastic reactions are small. We present cross sections together with their nuclear corrections for various channels which are useful for interpreting the experimental results and for determining parameters of the neutrino sector..Comment: 24 pages, 18 figure