Predicting B Cell Receptor Substitution Profiles Using Public Repertoire Data

B cells develop high affinity receptors during the course of affinity maturation, a cyclic process of mutation and selection. At the end of affinity maturation, a number of cells sharing the same ancestor (i.e. in the same "clonal family") are released from the germinal center, their amino acid frequency profile reflects the allowed and disallowed substitutions at each position. These clonal-family-specific frequency profiles, called "substitution profiles", are useful for studying the course of affinity maturation as well as for antibody engineering purposes. However, most often only a single sequence is recovered from each clonal family in a sequencing experiment, making it impossible to construct a clonal-family-specific substitution profile. Given the public release of many high-quality large B cell receptor datasets, one may ask whether it is possible to use such data in a prediction model for clonal-family-specific substitution profiles. In this paper, we present the method "Substitution Profiles Using Related Families" (SPURF), a penalized tensor regression framework that integrates information from a rich assemblage of datasets to predict the clonal-family-specific substitution profile for any single input sequence. Using this framework, we show that substitution profiles from similar clonal families can be leveraged together with simulated substitution profiles and germline gene sequence information to improve prediction. We fit this model on a large public dataset and validate the robustness of our approach on an external dataset. Furthermore, we provide a command-line tool in an open-source software package (https://github.com/krdav/SPURF) implementing these ideas and providing easy prediction using our pre-fit models.Comment: 23 page

Registration-based multi-orientation tomography

We propose a combination of an experimental approach and a reconstruction technique that leads to reduction of artefacts in X-ray computer tomography of strongly attenuating objects. Through fully automatic data alignment, data generated in multiple experiments with varying object orientations are combined. Simulations and exp

The Speech-Language Interface in the Spoken Language Translator

The Spoken Language Translator is a prototype for practically useful systems capable of translating continuous spoken language within restricted domains. The prototype system translates air travel (ATIS) queries from spoken English to spoken Swedish and to French. It is constructed, with as few modifications as possible, from existing pieces of speech and language processing software. The speech recognizer and language understander are connected by a fairly conventional pipelined N-best interface. This paper focuses on the ways in which the language processor makes intelligent use of the sentence hypotheses delivered by the recognizer. These ways include (1) producing modified hypotheses to reflect the possible presence of repairs in the uttered word sequence; (2) fast parsing with a version of the grammar automatically specialized to the more frequent constructions in the training corpus; and (3) allowing syntactic and semantic factors to interact with acoustic ones in the choice of a meaning structure for translation, so that the acoustically preferred hypothesis is not always selected even if it is within linguistic coverage.Comment: 9 pages, LaTeX. Published: Proceedings of TWLT-8, December 199

Iterative Automatic Segmentation in cardiac PET based on TAC correlation: preliminary results

Proceeding of: 2010 IEEE Nuclear Science Symposium, Medical Imaging Conference and 17th Room Temperature Semiconductor Detector Workshop (IEEE), Knoxville, Tennessee, USA, October 30 - November 6, 2010Conventional kinetic parameter estimation based on compartmental models requires an accurate estimation of arterial blood input function. To avoid invasive blood sampling, an image-derived input function can be obtained by manually defining a Region of Interest. Here we propose a new and simple, iterative method for automatic segmentation and input function calculation of PET cardiac studies using correlation as a distance metric between a priori information regarding the approximate shape of the final time-activity curve (TAC) and the actual TAC extracted from the image temporal series.This work was supported in part by the CENIT-AMIT Ingenio 2010, Ministerio de Ciencia e Innovación, TEC2007-64731, TEC 2008-06715-C02-1, RETIC-RECAVA, Ministerio de Sanidad y Consumo, and the ARTEMIS de la Comunidad de Madrid (S2009/DPI-1802) programsPublicad

Stellar Content from high resolution galactic spectra via Maximum A Posteriori

This paper describes STECMAP (STEllar Content via Maximum A Posteriori), a flexible, non-parametric inversion method for the interpretation of the integrated light spectra of galaxies, based on synthetic spectra of single stellar populations (SSPs). We focus on the recovery of a galaxy's star formation history and stellar age-metallicity relation. We use the high resolution SSPs produced by PEGASE-HR to quantify the informational content of the wavelength range 4000 - 6800 Angstroms. A detailed investigation of the properties of the corresponding simplified linear problem is performed using singular value decomposition. It turns out to be a powerful tool for explaining and predicting the behaviour of the inversion. We provide means of quantifying the fundamental limitations of the problem considering the intrinsic properties of the SSPs in the spectral range of interest, as well as the noise in these models and in the data. We performed a systematic simulation campaign and found that, when the time elapsed between two bursts of star formation is larger than 0.8 dex, the properties of each episode can be constrained with a precision of 0.04 dex in age and 0.02 dex in metallicity from high quality data (R=10 000, signal-to-noise ratio SNR=100 per pixel), not taking model errors into account. The described methods and error estimates will be useful in the design and in the analysis of extragalactic spectroscopic surveys.Comment: 31 pages, 23 figures, accepted for publication in MNRA