Exact Asymptotic Results for a Model of Sequence Alignment

Finding analytically the statistics of the longest common subsequence (LCS) of a pair of random sequences drawn from c alphabets is a challenging problem in computational evolutionary biology. We present exact asymptotic results for the distribution of the LCS in a simpler, yet nontrivial, variant of the original model called the Bernoulli matching (BM) model which reduces to the original model in the large c limit. We show that in the BM model, for all c, the distribution of the asymptotic length of the LCS, suitably scaled, is identical to the Tracy-Widom distribution of the largest eigenvalue of a random matrix whose entries are drawn from a Gaussian unitary ensemble. In particular, in the large c limit, this provides an exact expression for the asymptotic length distribution in the original LCS problem.Comment: 4 pages Revtex, 2 .eps figures include

Bethe Ansatz in the Bernoulli Matching Model of Random Sequence Alignment

For the Bernoulli Matching model of sequence alignment problem we apply the Bethe ansatz technique via an exact mapping to the 5--vertex model on a square lattice. Considering the terrace--like representation of the sequence alignment problem, we reproduce by the Bethe ansatz the results for the averaged length of the Longest Common Subsequence in Bernoulli approximation. In addition, we compute the average number of nucleation centers of the terraces.Comment: 14 pages, 5 figures (some points are clarified

Use of multiphoton tomography and fluorescence lifetime imaging to investigate skin pigmentation in vivo

There is a growing body of literature showing the usefulness of multiphoton tomography (MPT) and fluorescence lifetime imaging for in situ characterization of skin constituents and the ensuing development of noninvasive diagnostic tools against skin diseases. Melanin and pigmentation-associated skin cancers constitute some of the major applications. We show that MPT and fluorescence lifetime imaging can be used to measure changes in cutaneous melanin concentration and that these can be related to the visible skin color. Melanin in the skin of African, Indian, Caucasian, and Asian volunteers is detected on the basis of its emission wavelength and fluorescence lifetimes in solution and in a melanocyte-keratinocyte cell culture. Fluorescence intensity is used to characterize the melanin content and distribution as a function of skin type and depth into the skin (stratum granulosum and stratum basale). The measured fluorescence intensities in given skin types agree with melanin amounts reported by others using biopsies. Our results suggest that spatial distribution of melanin in skin can be studied using MPT and fluorescence lifetime imaging, but further studies are needed to ascertain that the method can resolve melanin amount in smaller depth intervals

Comparison of Spectra in Unsequenced Species

International audienceWe introduce a new algorithm for the mass spectromet- ric identication of proteins. Experimental spectra obtained by tandem MS/MS are directly compared to theoretical spectra generated from pro- teins of evolutionarily closely related organisms. This work is motivated by the need of a method that allows the identication of proteins of unsequenced species against a database containing proteins of related organisms. The idea is that matching spectra of unknown peptides to very similar MS/MS spectra generated from this database of annotated proteins can lead to annotate unknown proteins. This process is similar to ortholog annotation in protein sequence databases. The difficulty with such an approach is that two similar peptides, even with just one mod- ication (i.e. insertion, deletion or substitution of one or several amino acid(s)) between them, usually generate very dissimilar spectra. In this paper, we present a new dynamic programming based algorithm: Packet- SpectralAlignment. Our algorithm is tolerant to modications and fully exploits two important properties that are usually not considered: the notion of inner symmetry, a relation linking pairs of spectrum peaks, and the notion of packet inside each spectrum to keep related peaks together. Our algorithm, PacketSpectralAlignment is then compared to SpectralAlignment [1] on a dataset of simulated spectra. Our tests show that PacketSpectralAlignment behaves better, in terms of results and execution tim

Proper Alignment of MS/MS Spectra from Unsequenced Species

International audienceCorrect interpretation of tandem mass spectrom- etry (MS/MS) data is a critical step in the protein identifi- cation process. Comparing experimental spectra against a library of simulated spectra generated from a database is the most common strategy for this interpretation. Unfortunately, problems arise when treating unsequenced species since, in this case, the proteins to be identified are absent from the databanks and experimental spectra can only be compared to theoretical spectra from close and already sequenced organisms. In this context, spectra comparisons become a notoriously difficult problem. In this paper, we deal with this problem by considerably improving PacketSpectralAlignment ( PSA ), a method we presented in [1]. First, we explain how to take full advantage of PSA by carefully selecting the most promising alignment positions during the algorithm, and how to precisely fix the parameters of PSA . Second, we present a new method, referred to as PSAwEL , which allows a better localisation of modifications. We then propose a new peptide identification framework that integrates these improvements. Finally, we propose a comparison between PSA and the reference, SpectralAlignment [2], which shows that PSA behaves better in terms of: (i) quality of the results; and (ii) execution time. Our tests were conducted on the ISB dataset [3]. We then validate our new framework on Brachypod

Intraclonal Variation in Wood Density of Trembling Aspen in Alberta

Four trees from each of three putative clones of trembling aspen (Populus tremuloides Michx.) at one site in north-central Alberta were sampled to determine the patterns of wood density variation within stems and within clones. Sample disks were removed at five heights from each tree to examine variation among cardinal directions and across the southern radius at each height. Although only three clones were sampled, there were significant differences (0.05 level) among clones. Wood density tends to be high at the bottom of the tree, decreases to a minimum at midheight, then increases again near the top of the tree. In the radial direction, wood density is high near the pith (at all heights), decreases, then increases again in the mature wood zone (after rings 15-20+). Average wood density values within the twelve stems varied from 0.348 g/cc to 0.402 g/cc

Employing Dietary Comparators to Perform Risk Assessments for Anti-Androgens Without Using Animal Data

This study investigated the use of androgen receptor (AR) reporter gene assay data in a non-animal exposure-led risk assessment in which in vitro anti-androgenic activity and exposure data were put into context using a naturally occurring comparator substance with a history of dietary consumption. First, several dietary components were screened to identify which selectively interfered with AR signaling in vitro, using the AR CALUX® test. The IC50 values from these dose-response data together with measured or predicted human exposure levels were used to calculate exposure:activity ratios (EARs) for the dietary components and a number of other well-known anti-androgenic substances. Both diindolylmethane (DIM) and resveratrol are specifically-acting dietary anti-androgens. The EARs for several anti-androgens were therefore expressed relative to the EAR of DIM, and how this ‘dietary comparator ratio’ (DCR) approach may be used to make safety decisions was assessed using an exposure-led case study for an anti-androgenic botanical ingredient. This highlights a pragmatic approach which allows novel chemical exposures to be put into context against dietary exposures to natural anti-androgenic substances. The DCR approach may have utility for other modes of action where appropriate comparators can be identified