Bayesian DNA copy number analysis

BACKGROUND: Some diseases, like tumors, can be related to chromosomal aberrations, leading to changes of DNA copy number. The copy number of an aberrant genome can be represented as a piecewise constant function, since it can exhibit regions of deletions or gains. Instead, in a healthy cell the copy number is two because we inherit one copy of each chromosome from each our parents. Bayesian Piecewise Constant Regression (BPCR) is a Bayesian regression method for data that are noisy observations of a piecewise constant function. The method estimates the unknown segment number, the endpoints of the segments and the value of the segment levels of the underlying piecewise constant function. The Bayesian Regression Curve (BRC) estimates the same data with a smoothing curve. However, in the original formulation, some estimators failed to properly determine the corresponding parameters. For example, the boundary estimator did not take into account the dependency among the boundaries and succeeded in estimating more than one breakpoint at the same position, losing segments. RESULTS: We derived an improved version of the BPCR (called mBPCR) and BRC, changing the segment number estimator and the boundary estimator to enhance the fitting procedure. We also proposed an alternative estimator of the variance of the segment levels, which is useful in case of data with high noise. Using artificial data, we compared the original and the modified version of BPCR and BRC with other regression methods, showing that our improved version of BPCR generally outperformed all the others. Similar results were also observed on real data. CONCLUSION: We propose an improved method for DNA copy number estimation, mBPCR, which performed very well compared to previously published algorithms. In particular, mBPCR was more powerful in the detection of the true position of the breakpoints and of small aberrations in very noisy data. Hence, from a biological point of view, our method can be very useful, for example, to find targets of genomic aberrations in clinical cancer samples

An integrated Bayesian analysis of LOH and copy number data

BACKGROUND Cancer and other disorders are due to genomic lesions. SNP-microarrays are able to measure simultaneously both genotype and copy number (CN) at several Single Nucleotide Polymorphisms (SNPs) along the genome. CN is defined as the number of DNA copies, and the normal is two, since we have two copies of each chromosome. The genotype of a SNP is the status given by the nucleotides (alleles) which are present on the two copies of DNA. It is defined homozygous or heterozygous if the two alleles are the same or if they differ, respectively. Loss of heterozygosity (LOH) is the loss of the heterozygous status due to genomic events. Combining CN and LOH data, it is possible to better identify different types of genomic aberrations. For example, a long sequence of homozygous SNPs might be caused by either the physical loss of one copy or a uniparental disomy event (UPD), i.e. each SNP has two identical nucleotides both derived from only one parent. In this situation, the knowledge of the CN can help in distinguishing between these two events. RESULTS To better identify genomic aberrations, we propose a method (called gBPCR) which infers the type of aberration occurred, taking into account all the possible influence in the microarray detection of the homozygosity status of the SNPs, resulting from an altered CN level. Namely, we model the distributions of the detected genotype, given a specific genomic alteration and we estimate the parameters involved on public reference datasets. The estimation is performed similarly to the modified Bayesian Piecewise Constant Regression, but with improved estimators for the detection of the breakpoints.Using artificial and real data, we evaluate the quality of the estimation of gBPCR and we also show that it outperforms other well-known methods for LOH estimation. CONCLUSIONS We propose a method (gBPCR) for the estimation of both LOH and CN aberrations, improving their estimation by integrating both types of data and accounting for their relationships. Moreover, gBPCR performed very well in comparison with other methods for LOH estimation and the estimated CN lesions on real data have been validated with another technique.This work was supported by Swiss National Science Foundation (grants 205321-112430, 205320-121886/1); Oncosuisse grants OCS-1939-8-2006 and OCS - 02296-08-2008; Cantone Ticino ("Computational life science/Ticino in rete” program); Fondazione per la Ricerca e la Cura sui Linfomi (Lugano, Switzerland)

Pulsar Wind Nebulae as a source of the observed electron and positron excess at high energy: the case of Vela-X

We investigate, in terms of production from pulsars and their nebulae, the cosmic ray positron and electron fluxes above $\sim10$ GeV, observed by the AMS-02 experiment up to 1 TeV. We concentrate on the Vela-X case. Starting from the gamma-ray photon spectrum of the source, generated via synchrotron and inverse Compton processes, we estimated the electron and positron injection spectra. Several features are fixed from observations of Vela-X and unknown parameters are borrowed from the Crab nebula. The particle spectra produced in the pulsar wind nebula are then propagated up to the Solar System, using a diffusion model. Differently from previous works, the omnidirectional intensity excess for electrons and positrons is obtained as a difference between the AMS-02 data and the corresponding local interstellar spectrum. An equal amount of electron and positron excess is observed and we interpreted this excess (above $\sim$100 GeV in the AMS-02 data) as a supply coming from Vela-X. The particle contribution is consistent with models predicting the gamma-ray emission at the source. The input of a few more young pulsars is also allowed, while below $\sim$100 GeV more aged pulsars could be the main contributors.Comment: Accepted for publication in Journal of High Energy Astrophysics (2015

Possible Contribution to Electron and Positron Fluxes from Pulsars and their Nebulae

The AMS-02 experiment confirms the excess of positrons in cosmic rays (CRs) for energy above 10 GeV with respect to the secondary production of positrons in the interstellar medium. This is interpreted as evidence of the existence of a primary source of these particles. Possible candidates are dark matter or astrophysical sources. In this work we discuss the possible contribution due to pulsars and their nebulae. Our key assumption is that the primary spectrum of electrons and positrons at the source is the same of the well known photon spectrum observed from gamma-rays telescopes. Using a diffusion model in the Galaxy we propagate the source spectra up to the Solar System. We compare our results with the recent experiments and with the LIS modelComment: To appear in the Proceedings of the 14th ICATPP Conference, Villa Olmo 23-27 September 201

NIEL Dose Dependence for Solar Cells Irradiated with Electrons and Protons

The investigation of solar cells degradation and the prediction of its end-of-life performance is of primary importance in the preparation of a space mission. In the present work, we investigate the reduction of solar-cells' maximum power resulting from irradiations with electrons and protons. Both GaAs single junction and GaInP/GaAs/Ge triple junction solar cells were studied. The results obtained indicate how i) the dominant radiation damaging mechanism is due to atomic displacements, ii) the relative maximum power degradation is almost independent of the type of incoming particle, i.e., iii) to a first approximation, the fitted semi-empirical function expressing the decrease of maximum power depends only on the absorbed NIEL dose, and iv) the actual displacement threshold energy value (Ed=21 eV) accounts for annealing treatments, mostly due to self-annealing induced effects. Thus, for a given type of solar cell, a unique maximum power degradation curve can be determined as a function of the absorbed NIEL dose. The latter expression allows one to predict the performance of those solar cells in space radiation environment.Comment: To appear on the Proceedings of the 13th ICATPP Conference on Astroparticle, Particle, Space Physics and Detectors for Physics Applications, Villa Olmo (Como, Italy), 23--27 October, 2013, to be published by World Scientific (Singapore

FAST FRONT-END ELECTRONICS FOR EXPERIMENTS USING SILICON CALORIMETERS AT SSC /LHC COLLIDERS

Abstract A fast VLSI preamplifier using HF2CMOS technology was designed and built. The preamplifier meets the requirements for silicon calorimetry application in experiments at hadron colliders SSC/LHC. The overall power consumption is less than 45 mW for a maximum output voltage swing of 5 V (≈ 7 ns rise time). The slew rate is about 700 V/μs for an input capacitance of 150 pF. The measured value of ENC (equivalent noise charge), for an RC-CR shaping time of 20 ns and an input capacitance of 150 pF, is 17 ke RMS

Nuclear and Non-Ionizing Energy-Loss for Coulomb Scattered Particles from Low Energy up to Relativistic Regime in Space Radiation Environment

In the space environment, instruments onboard of spacecrafts can be affected by displacement damage due to radiation. The differential scattering cross section for screened nucleus--nucleus interactions - i.e., including the effects due to screened Coulomb nuclear fields -, nuclear stopping powers and non-ionization energy losses are treated from about 50 keV/nucleon up to relativistic energies.Comment: Accepted for publication in the Proceedings of the ICATPP Conference on Cosmic Rays for Particle and Astroparticle Physics, Villa Olmo (Como, Italy), 7--8 October, 2010, to be published by World Scientifi

Displacement Damage dose and DLTS Analyses on Triple and Single Junction solar cells irradiated with electrons and protons

Space solar cells radiation hardness is of fundamental importance in view of the future missions towards harsh radiation environment (like e.g. missions to Jupiter) and for the new spacecraft using electrical propulsion. In this paper we report the radiation data for triple junction (TJ) solar cells and related component cells. Triple junction solar cells, InGaP top cells and GaAs middle cells degrade after electron radiation as expected. With proton irradiation, a high spread in the remaining factors was observed, especially for the TJ and bottom cells. Very surprising was the germanium bottom junction that showed very high degradation after protons whereas it is quite stable against electrons. Radiation results have been analyzed by means of the Displacement Damage Dose method and DLTS spectroscopy.Comment: Abstract accepted for poster session at 2017 IEEE Nuclear and Space Radiation Effects Conference, July 17-21, New Orlean