6,177 research outputs found
Prediction and classification for GPCR sequences based on ligand specific features
Functional identification of G-Protein Coupled Receptors (GPCRs) is one of the current focus areas of pharmaceutical research. Although thousands of GPCR sequences are known, many of them are orphan sequences (the activating ligand is unknown). Therefore, classification methods for automated characterization of orphan GPCRs are imperative. In this study, for predicting Level 1 subfamilies of GPCRs, a novel method for obtaining class specific features, based on the existence of activating ligand specific patterns, has been developed and utilized for a majority voting classification. Exploiting the fact that there is a non-promiscuous relationship between the specific binding of GPCRs into their ligands and their functional classification, our method classifies Level 1 subfamilies of GPCRs with a high predictive accuracy between 99% and 87% in a three-fold cross validation test. The method also tells us which motifs are significant for class determination which has important design implications. The presented machine learning approach, bridges the gulf between the excess amount of GPCR sequence data and their poor functional characterization
Pseudorapidity Distribution of Charged Particles in PbarP Collisions at root(s)= 630GeV
Using a silicon vertex detector, we measure the charged particle
pseudorapidity distribution over the range 1.5 to 5.5 using data collected from
PbarP collisions at root s = 630 GeV. With a data sample of 3 million events,
we deduce a result with an overall normalization uncertainty of 5%, and typical
bin to bin errors of a few percent. We compare our result to the measurement of
UA5, and the distribution generated by the Lund Monte Carlo with default
settings. This is only the second measurement at this level of precision, and
only the second measurement for pseudorapidity greater than 3.Comment: 9 pages, 5 figures, LaTeX format. For ps file see
http://hep1.physics.wayne.edu/harr/harr.html Submitted to Physics Letters
On the hierarchical classification of G Protein-Coupled Receptors
Motivation: G protein-coupled receptors (GPCRs) play an important role in many physiological systems by transducing an extracellular signal into an intracellular response. Over 50% of all marketed drugs are targeted towards a GPCR. There is considerable interest in developing an algorithm that could effectively predict the function of a GPCR from its primary sequence. Such an algorithm is useful not only in identifying novel GPCR sequences but in characterizing the interrelationships between known GPCRs.
Results: An alignment-free approach to GPCR classification has been developed using techniques drawn from data mining and proteochemometrics. A dataset of over 8000 sequences was constructed to train the algorithm. This represents one of the largest GPCR datasets currently available. A predictive algorithm was developed based upon the simplest reasonable numerical representation of the protein's physicochemical properties. A selective top-down approach was developed, which used a hierarchical classifier to assign sequences to subdivisions within the GPCR hierarchy. The predictive performance of the algorithm was assessed against several standard data mining classifiers and further validated against Support Vector Machine-based GPCR prediction servers. The selective top-down approach achieves significantly higher accuracy than standard data mining methods in almost all cases
Accumulation of driver and passenger mutations during tumor progression
Major efforts to sequence cancer genomes are now occurring throughout the
world. Though the emerging data from these studies are illuminating, their
reconciliation with epidemiologic and clinical observations poses a major
challenge. In the current study, we provide a novel mathematical model that
begins to address this challenge. We model tumors as a discrete time branching
process that starts with a single driver mutation and proceeds as each new
driver mutation leads to a slightly increased rate of clonal expansion. Using
the model, we observe tremendous variation in the rate of tumor development -
providing an understanding of the heterogeneity in tumor sizes and development
times that have been observed by epidemiologists and clinicians. Furthermore,
the model provides a simple formula for the number of driver mutations as a
function of the total number of mutations in the tumor. Finally, when applied
to recent experimental data, the model allows us to calculate, for the first
time, the actual selective advantage provided by typical somatic mutations in
human tumors in situ. This selective advantage is surprisingly small, 0.005 +-
0.0005, and has major implications for experimental cancer research
A Hybrid Likelihood Model for Sequence-Based Disease Association Studies
In the past few years, case-control studies of common diseases have shifted their focus from single genes to whole exomes. New sequencing technologies now routinely detect hundreds of thousands of sequence variants in a single study, many of which are rare or even novel. The limitation of classical single-marker association analysis for rare variants has been a challenge in such studies. A new generation of statistical methods for case-control association studies has been developed to meet this challenge. A common approach to association analysis of rare variants is the burden-style collapsing methods to combine rare variant data within individuals across or within genes. Here, we propose a new hybrid likelihood model that combines a burden test with a test of the position distribution of variants. In extensive simulations and on empirical data from the Dallas Heart Study, the new model demonstrates consistently good power, in particular when applied to a gene set (e.g., multiple candidate genes with shared biological function or pathway), when rare variants cluster in key functional regions of a gene, and when protective variants are present. When applied to data from an ongoing sequencing study of bipolar disorder (191 cases, 107 controls), the model identifies seven gene sets with nominal p-values<0.05, of which one MAPK signaling pathway (KEGG) reaches trend-level significance after correcting for multiple testing. © 2013 Chen et al
Exact solution of a two-type branching process: Clone size distribution in cell division kinetics
We study a two-type branching process which provides excellent description of
experimental data on cell dynamics in skin tissue (Clayton et al., 2007). The
model involves only a single type of progenitor cell, and does not require
support from a self-renewed population of stem cells. The progenitor cells
divide and may differentiate into post-mitotic cells. We derive an exact
solution of this model in terms of generating functions for the total number of
cells, and for the number of cells of different types. We also deduce large
time asymptotic behaviors drawing on our exact results, and on an independent
diffusion approximation.Comment: 16 page
Atomic mass dependence of \Xi^- and \overline{\Xi}^+ production in central 250 GeV \pi^- nucleon interactions
We present the first measurement of the atomic mass dependence of central
\Xi^- and \overline{\Xi}^+ production. It is measured using a sample of 22,459
\Xi^-'s and \overline{\Xi}^+'s produced in collisions between a 250 GeV \pi^-
beam and targets of beryllium, aluminum, copper, and tungsten. The relative
cross sections are fit to the two parameter function \sigma_0 A^\alpha, where A
is the atomic mass. We measure \alpha = 0.924+-0.020+-0.025, for Feynman-x in
the range -0.09 < x_F < 0.15.Comment: 10 pages, revtex, 2 figures, submitted to Phys. Rev.
Construction and Performance of Large-Area Triple-GEM Prototypes for Future Upgrades of the CMS Forward Muon System
At present, part of the forward RPC muon system of the CMS detector at the
CERN LHC remains uninstrumented in the high-\eta region. An international
collaboration is investigating the possibility of covering the 1.6 < |\eta| <
2.4 region of the muon endcaps with large-area triple-GEM detectors. Given
their good spatial resolution, high rate capability, and radiation hardness,
these micro-pattern gas detectors are an appealing option for simultaneously
enhancing muon tracking and triggering capabilities in a future upgrade of the
CMS detector. A general overview of this feasibility study will be presented.
The design and construction of small (10\times10 cm2) and full-size trapezoidal
(1\times0.5 m2) triple-GEM prototypes will be described. During detector
assembly, different techniques for stretching the GEM foils were tested.
Results from measurements with x-rays and from test beam campaigns at the CERN
SPS will be shown for the small and large prototypes. Preliminary simulation
studies on the expected muon reconstruction and trigger performances of this
proposed upgraded muon system will be reported.Comment: 7 pages, 25 figures, submitted for publication in conference record
of the 2011 IEEE Nuclear Science Symposium, Valencia, Spai
An overview of the design, construction and performance of large area triple-GEM prototypes for future upgrades of the CMS forward muon system
GEM detectors are used in high energy physics experiments given their good spatial resolution, high rate capability and radiation hardness. An international collaboration is investigating the possibility of covering the 1.6 < vertical bar eta vertical bar < 2.4 region of the CMS muon endcaps with large-area triple-GEM detectors. The CMS high-eta area is actually not fully instrumented, only Cathode Strip Chamber (CSC) are installed. The vacant area presents an opportunity for a detector technology able to to cope with the harsh radiation environment; these micropattern gas detectors are an appealing option to simultaneously enhance muon tracking and triggering capabilities in a future upgrade of the CMS detector. A general overview of this feasibility study is presented. Design and construction of small (10cm x 10cm) and full-size trapezoidal (1m x 0.5m) triple-GEM prototypes is described. Results from measurements with x-rays and from test beam campaigns at the CERN SPS is shown for the small and large prototypes. Preliminary simulation studies on the expected muon reconstruction and trigger performances of this proposed upgraded muon system are reported
Operational experience with the GEM detector assembly lines for the CMS forward muon upgrade
The CMS Collaboration has been developing large-area triple-gas electron multiplier (GEM) detectors to be installed in the muon Endcap regions of the CMS experiment in 2019 to maintain forward muon trigger and tracking performance at the High-Luminosity upgrade of the Large Hadron Collider (LHC); 10 preproduction detectors were built at CERN to commission the first assembly line and the quality controls (QCs). These were installed in the CMS detector in early 2017 and participated in the 2017 LHC run. The collaboration has prepared several additional assembly and QC lines for distributed mass production of 160 GEM detectors at various sites worldwide. In 2017, these additional production sites have optimized construction techniques and QC procedures and validated them against common specifications by constructing additional preproduction detectors. Using the specific experience from one production site as an example, we discuss how the QCs make use of independent hardware and trained personnel to ensure fast and reliable production. Preliminary results on the construction status of CMS GEM detectors are presented with details of the assembly sites involvement
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