ISOWN: accurate somatic mutation identification in the absence of normal tissue controls.

BackgroundA key step in cancer genome analysis is the identification of somatic mutations in the tumor. This is typically done by comparing the genome of the tumor to the reference genome sequence derived from a normal tissue taken from the same donor. However, there are a variety of common scenarios in which matched normal tissue is not available for comparison.ResultsIn this work, we describe an algorithm to distinguish somatic single nucleotide variants (SNVs) in next-generation sequencing data from germline polymorphisms in the absence of normal samples using a machine learning approach. Our algorithm was evaluated using a family of supervised learning classifications across six different cancer types and ~1600 samples, including cell lines, fresh frozen tissues, and formalin-fixed paraffin-embedded tissues; we tested our algorithm with both deep targeted and whole-exome sequencing data. Our algorithm correctly classified between 95 and 98% of somatic mutations with F1-measure ranges from 75.9 to 98.6% depending on the tumor type. We have released the algorithm as a software package called ISOWN (Identification of SOmatic mutations Without matching Normal tissues).ConclusionsIn this work, we describe the development, implementation, and validation of ISOWN, an accurate algorithm for predicting somatic mutations in cancer tissues in the absence of matching normal tissues. ISOWN is available as Open Source under Apache License 2.0 from https://github.com/ikalatskaya/ISOWN

Molecular dynamics of folding of secondary structures in Go-type models of proteins

We consider six different secondary structures of proteins and construct two types of Go-type off-lattice models: with the steric constraints and without. The basic aminoacid-aminoacid potential is Lennard Jones for the native contacts and a soft repulsion for the non-native contacts. The interactions are chosen to make the target secondary structure be the native state of the system. We provide a thorough equilibrium and kinetic characterization of the sequences through the molecular dynamics simulations with the Langevin noise. Models with the steric constraints are found to be better folders and to be more stable, especially in the case of the $\beta$-structures. Phononic spectra for vibrations around the native states have low frequency gaps that correlate with the thermodynamic stability. Folding of the secondary structures proceeds through a well defined sequence of events. For instance, $\alpha$-helices fold from the ends first. The closer to the native state, the faster establishment of the contacts. Increasing the system size deteriorates the folding characteristics. We study the folding times as a function of viscous friction and find a regime of moderate friction with the linear dependence. We also consider folding when one end of a structure is pinned which imitates instantaneous conditions when a protein is being synthesized. We find that, under such circumstances, folding of helices is faster and of the $\beta$-sequences slower.Comment: REVTeX, 14 pages, EPS figures included, JCP in pres

A new root-knot nematode, Meloidogyne moensi n. sp. (Nematoda : Meloidogynidae), parasitizing Robusta coffee from Western Highlands, Vietnam

A new root-knot nematode, parasitizing Robusta coffee in Dak Lak Province, Western Highlands of Vietnam, is described as Meloidogyne moensi n. sp. Morphological and molecular analyses demonstrated that this species differs clearly from other previously described root-knot nematodes. Morphologically, the new species is characterized by a swollen body of females with a small posterior protuberance that elongated from ovoid to saccate; perineal patterns with smooth striae, continuous and low dorsal arch; lateral lines marked as a faint space or linear depression at junction of the dorsal and ventral striate; distinct phasmids; perivulval region free of striae; visible and wide tail terminus surrounding by concentric circles of striae; medial lips of females in dumbbell-shaped and slightly raised above lateral lips; female stylet is normally straight with posteriorly sloping stylet knobs; lip region of second stage juvenile (J2) is not annulated; medial lips and labial disc of J2 formed dumbbell shape; lateral lips are large and triangular; tail of J2 is conoid with rounded unstriated tail tip; distinct phasmids and hyaline; dilated rectum. Meloidogyne moensi n. sp. is most similar to M. africana, M. ottersoni by prominent posterior protuberance. Results of molecular analysis of rDNA sequences including the D2-D3 expansion regions of 28S rDNA, COI, and partial COII/16S rRNA of mitochondrial DNA support for the new species status

The Spitzer View of Low-Metallicity Star Formation: II. Mrk 996, a Blue Compact Dwarf Galaxy with an Extremely Dense Nucleus

(abridged) We present new Spitzer, UKIRT and MMT observations of the blue compact dwarf galaxy (BCD) Mrk 996, with an oxygen abundance of 12+log(O/H)=8.0. This galaxy has the peculiarity of possessing an extraordinarily dense nuclear star-forming region, with a central density of ~10^6 cm^{-3}. The nuclear region of Mrk 996 is characterized by several unusual properties: a very red color J-K = 1.8, broad and narrow emission-line components, and ionizing radiation as hard as 54.9 eV, as implied by the presence of the OIV 25.89 micron line. The nucleus is located within an exponential disk with colors consistent with a single stellar population of age >1 Gyr. The infrared morphology of Mrk 996 changes with wavelength. The IRS spectrum shows strong narrow Polycyclic Aromatic Hydrocarbon (PAH) emission, with narrow line widths and equivalent widths that are high for the metallicity of Mrk 996. Gaseous nebular fine-structure lines are also seen. A CLOUDY model requires that they originate in two distinct HII regions: a very dense HII region of radius ~580 pc with densities declining from ~10^6 at the center to a few hundreds cm^{-3} at the outer radius, where most of the optical lines arise; and a HII region with a density of ~300 cm^{-3} that is hidden in the optical but seen in the MIR. We suggest that the infrared lines arise mainly in the optically obscured HII region while they are strongly suppressed by collisional deexcitation in the optically visible one. The hard ionizing radiation needed to account for the OIV 25.89 micron line is most likely due to fast radiative shocks propagating in an interstellar medium. A hidden population of Wolf-Rayet stars of type WNE-w or a hidden AGN as sources of hard ionizing radiation are less likely possibilities.Comment: 48 pages, 13 figures, accepted for publication in the Astrophysical Journa

Calculation of the Hidden Symmetry Operator in PT-Symmetric Quantum Mechanics

In a recent paper it was shown that if a Hamiltonian H has an unbroken PT symmetry, then it also possesses a hidden symmetry represented by the linear operator C. The operator C commutes with both H and PT. The inner product with respect to CPT is associated with a positive norm and the quantum theory built on the associated Hilbert space is unitary. In this paper it is shown how to construct the operator C for the non-Hermitian PT-symmetric Hamiltonian $H={1\over2}p^2+{1\over2}x^2 +i\epsilon x^3$ using perturbative techniques. It is also shown how to construct the operator C for $H={1\over2}p^2+{1\over2}x^2-\epsilon x^4$ using nonperturbative methods

Analytic calculation of radio emission from parametrized extensive air showers:A tool to extract shower parameters

The radio intensity and polarization footprint of a cosmic-ray induced extensive air shower is determined by the time-dependent structure of the current distribution residing in the plasma cloud at the shower front. In turn, the time dependence of the integrated charge-current distribution in the plasma cloud, the longitudinal shower structure, is determined by interesting physics which one would like to extract, such as the location and multiplicity of the primary cosmic-ray collision or the values of electric fields in the atmosphere during thunderstorms. To extract the structure of a shower from its footprint requires solving a complicated inverse problem. For this purposewe have developed a code that semianalytically calculates the radio footprint of an extensive air shower given an arbitrary longitudinal structure. This code can be used in an optimization procedure to extract the optimal longitudinal shower structure given a radio footprint. On the basis of air-shower universality we propose a simple parametrization of the structure of the plasma cloud. This parametrization is based on the results of Monte Carlo shower simulations. Deriving the parametrization also teaches which aspects of the plasma cloud are important for understanding the features seen in the radio-emission footprint. The calculated radio footprints are compared with microscopic CoREAS simulations