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Biomedical subjects

I Pe'er

Publications and source records attributed to I Pe'er.

5 recordsLinked to original sources

On the complexity of positional sequencing by hybridization.

In sequencing by hybridization (SBH), one has to reconstruct a sequence from its l-long substrings. SBH was proposed as an alternative to gel-based DNA sequencing approaches, but in its original form the method is not competitive. Positional SBH (PSBH) is a recently proposed enhancement of SBH in which one has additional information about the possible positions of each substring along the target sequence. We give a linear time algorithm for solving PSBH when each substring has at most two possible positions. On the other hand, we prove that the problem is NP-complete if each substring has at most three possible positions. We also show that PSBH is NP-complete if the set of allowed positions for each substring is an interval of length k and provide a fast algorithm for the latter problem when k is bounded.

Algorithms↗

An algorithm combining discrete and continuous methods for optical mapping.

Optical mapping is a novel technique for generating the restriction map of a DNA molecule by observing many single, partially digested copies of it, using fluorescence microscopy. The real-life problem is complicated by numerous factors: false positive and false negative cut observations, inaccurate location measurements, unknown orientations, and faulty molecules. We present an algorithm for solving the real-life problem. The algorithm combines continuous optimization and combinatorial algorithms applied to a nonuniform discretization of the data. We present encouraging results on real experimental data and on simulated data.

Algorithms↗

A fast algorithm for joint reconstruction of ancestral amino acid sequences.

A dynamic programming algorithm is developed for maximum-likelihood reconstruction of the set of all ancestral amino acid sequences in a phylogenetic tree. To date, exhaustive algorithms that find the most likely set of ancestral states (joint reconstruction) have running times that scale exponentially with the number of sequences and are thus limited to very few taxa. The time requirement of our new algorithm scales linearly with the number of sequences and is therefore applicable to practically any number of taxa. A detailed description of the new algorithm and an example of its application to cytochrome b sequences are provided.

Algorithms↗

Spectrum alignment: efficient resequencing by hybridization.

Recent high-density microarray technologies allow, in principle, the determination of all k-mers that appear along a DNA sequence, for k = 8 - 10 in a single experiment on a standard chip. The k-mer contents, also called the spectrum of the sequence, is not sufficient to uniquely reconstruct a sequence longer than a few hundred bases. We have devised a polynomial algorithm that reconstructs the sequence, given the spectrum and a homologous sequence. This situation occurs, for example, in the identification of single nucleotide polymorphisms (SNPs), and whenever a homologue of the target sequence is known. The algorithm is robust, can handle errors in the spectrum and assumes no knowledge of the k-mer multiplicities. Our simulations show that with realistic levels of SNPs, the algorithm correctly reconstructs a target sequence of length up to 2,000 nucleotides when a polymorphic sequence is known. The technique is generalized to handle profiles and HMMs as input instead of a single homologous sequence.

Algorithms↗

An algorithm combining discrete and continuous methods for optical mapping.

Optical mapping is a novel technique for generating the restriction map of a DNA molecule by observing many single, partially digested, copies of it, using fluorescence microscopy. The real-life problem is complicated by numerous factors: false positive and false negative cut observations, inaccurate location measurements, unknown orientations and faulty molecules. We present an algorithm for solving the real-life problem. The algorithm combines continuous optimization and combinatorial algorithms, applied to a non-uniform discretization of the data. We present encouraging results on real experimental data.

Algorithms↗