Physicochemical property distributions for accurate and rapid pairwise protein homology detection

<p>Abstract</p> <p>Background</p> <p>The challenge of remote homology detection is that many evolutionarily related sequences have very little similarity at the amino acid level. Kernel-based discriminative methods, such as support vector machines (SVMs), that use vector representations of sequences derived from sequence properties have been shown to have superior accuracy when compared to traditional approaches for the task of remote homology detection.</p> <p>Results</p> <p>We introduce a new method for feature vector representation based on the physicochemical properties of the primary protein sequence. A distribution of physicochemical property scores are assembled from 4-mers of the sequence and normalized based on the null distribution of the property over all possible 4-mers. With this approach there is little computational cost associated with the transformation of the protein into feature space, and overall performance in terms of remote homology detection is comparable with current state-of-the-art methods. We demonstrate that the features can be used for the task of pairwise remote homology detection with improved accuracy versus sequence-based methods such as BLAST and other feature-based methods of similar computational cost.</p> <p>Conclusions</p> <p>A protein feature method based on physicochemical properties is a viable approach for extracting features in a computationally inexpensive manner while retaining the sensitivity of SVM protein homology detection. Furthermore, identifying features that can be used for generic pairwise homology detection in lieu of family-based homology detection is important for applications such as large database searches and comparative genomics.</p

A defect in myoblast fusion underlies Carey-Fineman-Ziter syndrome

Multinucleate cellular syncytial formation is a hallmark of skeletal muscle differentiation. Myomaker, encoded by Mymk (Tmem8c), is a well-conserved plasma membrane protein required for myoblast fusion to form multinucleated myotubes in mouse, chick, and zebrafish. Here, we report that autosomal recessive mutations in MYMK (OMIM 615345) cause Carey-Fineman-Ziter syndrome in humans (CFZS; OMIM 254940) by reducing but not eliminating MYMK function. We characterize MYMK-CFZS as a congenital myopathy with marked facial weakness and additional clinical and pathologic features that distinguish it from other congenital neuromuscular syndromes. We show that a heterologous cell fusion assay in vitro and allelic complementation experiments in mymk knockdown and mymk insT/insT zebrafish in vivo can differentiate between MYMK wild type, hypomorphic and null alleles. Collectively, these data establish that MYMK activity is necessary for normal muscle development and maintenance in humans, and expand the spectrum of congenital myopathies to include cell-cell fusion deficits

A roadmap for the Human Developmental Cell Atlas

The Human Developmental Cell Atlas (HDCA) initiative, which is part of the Human Cell Atlas, aims to create a comprehensive reference map of cells during development. This will be critical to understanding normal organogenesis, the effect of mutations, environmental factors and infectious agents on human development, congenital and childhood disorders, and the cellular basis of ageing, cancer and regenerative medicine. Here we outline the HDCA initiative and the challenges of mapping and modelling human development using state-of-the-art technologies to create a reference atlas across gestation. Similar to the Human Genome Project, the HDCA will integrate the output from a growing community of scientists who are mapping human development into a unified atlas. We describe the early milestones that have been achieved and the use of human stem-cell-derived cultures, organoids and animal models to inform the HDCA, especially for prenatal tissues that are hard to acquire. Finally, we provide a roadmap towards a complete atlas of human development

Search for a Technicolor omega_T Particle in Events with a Photon and a b-quark Jet at CDF

If the Technicolor omega_T particle exists, a likely decay mode is omega_T -> gamma pi_T, followed by pi_T -> bb-bar, yielding the signature gamma bb-bar. We have searched 85 pb^-1 of data collected by the CDF experiment at the Fermilab Tevatron for events with a photon and two jets, where one of the jets must contain a secondary vertex implying the presence of a b quark. We find no excess of events above standard model expectations. We express the result of an exclusion region in the M_omega_T - M_pi_T mass plane.Comment: 14 pages, 2 figures. Available from the CDF server (PS with figs): http://www-cdf.fnal.gov/physics/pub98/cdf4674_omega_t_prl_4.ps FERMILAB-PUB-98/321-

Measurement of the B0 anti-B0 oscillation frequency using l- D*+ pairs and lepton flavor tags

The oscillation frequency Delta-md of B0 anti-B0 mixing is measured using the partially reconstructed semileptonic decay anti-B0 -> l- nubar D*+ X. The data sample was collected with the CDF detector at the Fermilab Tevatron collider during 1992 - 1995 by triggering on the existence of two lepton candidates in an event, and corresponds to about 110 pb-1 of pbar p collisions at sqrt(s) = 1.8 TeV. We estimate the proper decay time of the anti-B0 meson from the measured decay length and reconstructed momentum of the l- D*+ system. The charge of the lepton in the final state identifies the flavor of the anti-B0 meson at its decay. The second lepton in the event is used to infer the flavor of the anti-B0 meson at production. We measure the oscillation frequency to be Delta-md = 0.516 +/- 0.099 +0.029 -0.035 ps-1, where the first uncertainty is statistical and the second is systematic.Comment: 30 pages, 7 figures. Submitted to Physical Review

Diffractive Dijet Production at sqrt(s)=630 and 1800 GeV at the Fermilab Tevatron

We report a measurement of the diffractive structure function $F_{jj}^D$ of the antiproton obtained from a study of dijet events produced in association with a leading antiproton in $\bar pp$ collisions at $\sqrt s=630$ GeV at the Fermilab Tevatron. The ratio of $F_{jj}^D$ at $\sqrt s=630$ GeV to $F_{jj}^D$ obtained from a similar measurement at $\sqrt s=1800$ GeV is compared with expectations from QCD factorization and with theoretical predictions. We also report a measurement of the $\xi$ ($x$-Pomeron) and $\beta$ ($x$ of parton in Pomeron) dependence of $F_{jj}^D$ at $\sqrt s=1800$ GeV. In the region $0.035<\xi<0.095$, $|t|<1$ GeV$^2$ and $\beta<0.5$, $F_{jj}^D(\beta,\xi)$ is found to be of the form $\beta^{-1.0\pm 0.1} \xi^{-0.9\pm 0.1}$, which obeys $\beta$-$\xi$ factorization.Comment: LaTeX, 9 pages, Submitted to Phys. Rev. Letter

Search for New Particles Decaying to top-antitop in proton-antiproton collisions at squareroot(s)=1.8 TeV

We use 106 \ipb of data collected with the Collider Detector at Fermilab to search for narrow-width, vector particles decaying to a top and an anti-top quark. Model independent upper limits on the cross section for narrow, vector resonances decaying to \ttbar are presented. At the 95% confidence level, we exclude the existence of a leptophobic \zpr boson in a model of topcolor-assisted technicolor with mass M_{\zpr} $<$ 480 \gev for natural width $\Gamma$ = 0.012 M_{\zpr}, and M_{\zpr} $<$ 780 \gev for $\Gamma$ = 0.04 M_{\zpr}.Comment: The CDF Collaboration, submitted to PRL 25-Feb-200

Double Diffraction Dissociation at the Fermilab Tevatron Collider

We present results from a measurement of double diffraction dissociation in $\bar pp$ collisions at the Fermilab Tevatron collider. The production cross section for events with a central pseudorapidity gap of width $\Delta\eta^0>3$ (overlapping $\eta=0$) is found to be $4.43\pm 0.02{(stat)}{\pm 1.18}{(syst) mb}$ [$3.42\pm 0.01{(stat)}{\pm 1.09}{(syst) mb}$] at $\sqrt{s}=1800$ [630] GeV. Our results are compared with previous measurements and with predictions based on Regge theory and factorization.Comment: 10 pages, 4 figures, using RevTeX. Submitted to Physical Review Letter

A Measurement of the Differential Dijet Mass Cross Section in p-pbar Collisions at sqrt{s}=1.8 TeV

We present a measurement of the cross section for production of two or more jets as a function of dijet mass, based on an integrated luminosity of 86 pb^-1 collected with the Collider Detector at Fermilab. Our dijet mass spectrum is described within errors by next-to-leading order QCD predictions using CTEQ4HJ parton distributions, and is in good agreement with a similar measurement from the D0 experiment.Comment: 18 pages including 2 figures and 3 tables. Submitted to Phys. Rev. D Rapid Communication

Search for Gluinos and Scalar Quarks in ppˉp\bar{p} Collisions at s=1.8\sqrt{s}=1.8 TeV using the Missing Energy plus Multijets Signature

We have performed a search for gluinos (\gls) and squarks (\sq) in a data sample of 84 pb$^{-1}$ of \ppb collisions at $\sqrt{s}$ = 1.8 TeV, recorded by the Collider Detector at Fermilab, by investigating the final state of large missing transverse energy and 3 or more jets, a characteristic signature in R-parity-conserving supersymmetric models. The analysis has been performed `blind', in that the inspection of the signal region is made only after the predictions from Standard Model backgrounds have been calculated. Comparing the data with predictions of constrained supersymmetric models, we exclude gluino masses below 195 \gev (95% C.L.), independent of the squark mass. For the case \msq \approx \mgls, gluino masses below 300 \gev are excluded.Comment: 7 pages, 3 figure