Characterising ChIP-seq binding patterns by model-based peak shape deconvolution

BACKGROUND: Chromatin immunoprecipitation combined with massive parallel sequencing (ChIP-seq) is widely used to study protein-chromatin interactions or chromatin modifications at genome-wide level. Sequence reads that accumulate locally at the genome (peaks) reveal loci of selectively modified chromatin or specific sites of chromatin-binding factors. Computational approaches (peak callers) have been developed to identify the global pattern of these sites, most of which assess the deviation from background by applying distribution statistics. RESULTS: We have implemented MeDiChISeq, a regression-based approach, which--by following a learning process--defines a representative binding pattern from the investigated ChIP-seq dataset. Using this model MeDiChISeq identifies significant genome-wide patterns of chromatin-bound factors or chromatin modification. MeDiChISeq has been validated for various publicly available ChIP-seq datasets and extensively compared with other peak callers. CONCLUSIONS: MeDiChI-Seq has a high resolution when identifying binding events, a high degree of peak-assessment reproducibility in biological replicates, a low level of false calls and a high true discovery rate when evaluated in the context of gold-standard benchmark datasets. Importantly, this approach can be applied not only to 'sharp' binding patterns--like those retrieved for transcription factors (TFs)--but also to the broad binding patterns seen for several histone modifications. Notably, we show that at high sequencing depths, MeDiChISeq outperforms other algorithms due to its powerful peak shape recognition capacity which facilitates discerning significant binding events from spurious background enrichment patterns that are enhanced with increased sequencing depths

A spring search algorithm applied to engineering optimization problems

At present, optimization algorithms are used extensively. One particular type of such algorithms includes random-based heuristic population optimization algorithms, which may be created by modeling scientific phenomena, like, for example, physical processes. The present article proposes a novel optimization algorithm based on Hooke’s law, called the spring search algorithm (SSA), which aims to solve single-objective constrained optimization problems. In the SSA, search agents are weights joined through springs, which, as Hooke’s law states, possess a force that corresponds to its length. The mathematics behind the algorithm are presented in the text. In order to test its functionality, it is executed on 38 established benchmark test functions and weighed against eight other optimization algorithms: a genetic algorithm (GA), a gravitational search algorithm (GSA), a grasshopper optimization algorithm (GOA), particle swarm optimization (PSO), teaching–learning-based optimization (TLBO), a grey wolf optimizer (GWO), a spotted hyena optimizer (SHO), as well as an emperor penguin optimizer (EPO). To test the SSA’s usability, it is employed on five engineering optimization problems. The SSA delivered better fitting results than the other algorithms in unimodal objective function, multimodal objective functions, CEC 2015, in addition to the optimization problems in engineering

Nucleic Acids Res

The absence of a quality control (QC) system is a major weakness for the comparative analysis of genome-wide profiles generated by next-generation sequencing (NGS). This concerns particularly genome binding/occupancy profiling assays like chromatin immunoprecipitation (ChIP-seq) but also related enrichment-based studies like methylated DNA immunoprecipitation/methylated DNA binding domain sequencing, global run on sequencing or RNA-seq. Importantly, QC assessment may significantly improve multidimensional comparisons that have great promise for extracting information from combinatorial analyses of the global profiles established for chromatin modifications, the bindings of epigenetic and chromatin-modifying enzymes/machineries, RNA polymerases and transcription factors and total, nascent or ribosome-bound RNAs. Here we present an approach that associates global and local QC indicators to ChIP-seq data sets as well as to a variety of enrichment-based studies by NGS. This QC system was used to certify >5600 publicly available data sets, hosted in a database for data mining and comparative QC analyses

Single hadron response measurement and calorimeter jet energy scale uncertainty with the ATLAS detector at the LHC

The uncertainty on the calorimeter energy response to jets of particles is derived for the ATLAS experiment at the Large Hadron Collider (LHC). First, the calorimeter response to single isolated charged hadrons is measured and compared to the Monte Carlo simulation using proton-proton collisions at centre-of-mass energies of sqrt(s) = 900 GeV and 7 TeV collected during 2009 and 2010. Then, using the decay of K_s and Lambda particles, the calorimeter response to specific types of particles (positively and negatively charged pions, protons, and anti-protons) is measured and compared to the Monte Carlo predictions. Finally, the jet energy scale uncertainty is determined by propagating the response uncertainty for single charged and neutral particles to jets. The response uncertainty is 2-5% for central isolated hadrons and 1-3% for the final calorimeter jet energy scale.Comment: 24 pages plus author list (36 pages total), 23 figures, 1 table, submitted to European Physical Journal

Measurement of χ c1 and χ c2 production with s√ = 7 TeV pp collisions at ATLAS

The prompt and non-prompt production cross-sections for the χ c1 and χ c2 charmonium states are measured in pp collisions at s√ = 7 TeV with the ATLAS detector at the LHC using 4.5 fb−1 of integrated luminosity. The χ c states are reconstructed through the radiative decay χ c → J/ψγ (with J/ψ → μ + μ −) where photons are reconstructed from γ → e + e − conversions. The production rate of the χ c2 state relative to the χ c1 state is measured for prompt and non-prompt χ c as a function of J/ψ transverse momentum. The prompt χ c cross-sections are combined with existing measurements of prompt J/ψ production to derive the fraction of prompt J/ψ produced in feed-down from χ c decays. The fractions of χ c1 and χ c2 produced in b-hadron decays are also measured

Measurement of the flavour composition of dijet events in pp collisions at root s=7 TeV with the ATLAS detector

This paper describes a measurement of the flavour composition of dijet events produced in pp collisions at √s=7 TeV using the ATLAS detector. The measurement uses the full 2010 data sample, corresponding to an integrated luminosity of 39 pb−1. Six possible combinations of light, charm and bottom jets are identified in the dijet events, where the jet flavour is defined by the presence of bottom, charm or solely light flavour hadrons in the jet. Kinematic variables, based on the properties of displaced decay vertices and optimised for jet flavour identification, are used in a multidimensional template fit to measure the fractions of these dijet flavour states as functions of the leading jet transverse momentum in the range 40 GeV to 500 GeV and jet rapidity |y|<2.1. The fit results agree with the predictions of leading- and next-to-leading-order calculations, with the exception of the dijet fraction composed of bottom and light flavour jets, which is underestimated by all models at large transverse jet momenta. The ability to identify jets containing two b-hadrons, originating from e.g. gluon splitting, is demonstrated. The difference between bottom jet production rates in leading and subleading jets is consistent with the next-to-leading-order predictions

Measurement of the production of a W boson in association with a charm quark in pp collisions at √s = 7 TeV with the ATLAS detector

The production of a W boson in association with a single charm quark is studied using 4.6 fb−1 of pp collision data at s√ = 7 TeV collected with the ATLAS detector at the Large Hadron Collider. In events in which a W boson decays to an electron or muon, the charm quark is tagged either by its semileptonic decay to a muon or by the presence of a charmed meson. The integrated and differential cross sections as a function of the pseudorapidity of the lepton from the W-boson decay are measured. Results are compared to the predictions of next-to-leading-order QCD calculations obtained from various parton distribution function parameterisations. The ratio of the strange-to-down sea-quark distributions is determined to be 0.96+0.26−0.30 at Q 2 = 1.9 GeV2, which supports the hypothesis of an SU(3)-symmetric composition of the light-quark sea. Additionally, the cross-section ratio σ(W + +c¯¯)/σ(W − + c) is compared to the predictions obtained using parton distribution function parameterisations with different assumptions about the s−s¯¯¯ quark asymmetry

Observation of top-quark pair production in association with a photon and measurement of the ttγ production cross section in pp collisions at √s = 7 TeV using the ATLAS detector

A search is performed for top-quark pairs (tt) produced together with a photon (γ) with transverse energy greater than 20 GeV using a sample of tt candidate events in final states with jets, missing transverse momentum, and one isolated electron or muon. The data set used corresponds to an integrated luminosity of 4.59 fb −1 of proton-proton collisions at a center-of-mass energy of 7 TeV recorded by the ATLAS detector at the CERN Large Hadron Collider. In total, 140 and 222 ttγ candidate events are observed in the electron and muon channels, to be compared to the expectation of 79 +/- 26 and 120 +/- 39 non-ttγ background events, respectively. The production of ttγ events is observed with a significance of 5.3 standard deviations away from the null hypothesis. The ttγ production cross section times the branching ratio (BR) of the single-lepton decay channel is measured in a fiducial kinematic region within the ATLAS acceptance. The measured value is σ (fid/tty) × BR = 63 +/- 8(stat) (+17/-13)(syst) +/- 1 lumi fb per lepton flavor, in good agreement with the leading-order theoretical calculation normalized to the next-to-leading-order theoretical prediction of 48 +/- 10 fb

Search for a CP-odd Higgs boson decaying to Zh in pp collisions at √s=8TeV with the ATLAS detector

A search for a heavy, CP-odd Higgs boson, A, decaying into a Zboson and a 125GeV Higgs boson, h, with the ATLAS detector at the LHC is presented. The search uses proton–proton collision data at a centre-of-mass energy of 8TeV corresponding to an integrated luminosity of 20.3fb−1. Decays of CP-even hbosons to ττor bbpairs with the Zboson decaying to electron or muon pairs are considered, as well as h →bbdecays with the Zboson decaying to neutrinos. No evidence for the production of an Aboson in these channels is found and the 95% confidence level upper limits derived for σ(gg→A) ×BR(A →Zh) ×BR(h →f¯f)are 0.098–0.013pb for f=τand 0.57–0.014pb for f=bin a range of mA=220–1000GeV. The results are combined and interpreted in the context of two-Higgs-doublet models. Published by Elsevier B.V. This is an open access article under the CC BY license (http://creativecommons