Scott Schwartz

A Greedy Algorithm for Aligning DNA Sequences

For aligning DNA sequences that differ only by sequencing errors, or by equivalent errors from other sources, a greedy algorithm can be much faster than traditional dynamic programming approaches and yet produce an alignment that is guaranteed to be theoretically optimal. We introduce a new greedy alignment algorithm with particularly good performance and show that it computes the same alignment as does a certain dynamic programming algorithm, while executing over 10 times faster on appropriate data. An implementation of this algorithm is currently used in a program that assembles the UniGene database at the National Center for Biotechnology Information.

Comparative analyses of multi-species sequences from targeted genomic regions

The systematic comparison of genomic sequences from different organisms represents a central focus of contemporary genome analysis. Comparative analyses of vertebrate sequences can identify coding and conserved non-coding regions, including regulatory elements, and provide insight into the forces that have rendered modern-day genomes. As a complement to whole-genome sequencing efforts, we are sequencing and comparing targeted genomic regions in multiple, evolutionarily diverse vertebrates. Here we report the generation and analysis of over 12 megabases (Mb) of sequence from 12 species, all derived from the genomic region orthologous to a segment of about 1.8 Mb on human chromosome 7 containing ten genes, including the gene mutated in cystic fibrosis. These sequences show conservation reflecting both functional constraints and the neutral mutational events that shaped this genomic region. In particular, we identify substantial numbers of conserved non-coding segments beyond those previously identified experimentally, most of which are not detectable by pair-wise sequence comparisons alone. Analysis of transposable element insertions highlights the variation in genome dynamics among these species and confirms the placement of rodents as a sister group to the primates.

Parallelization of a local similarity algorithm

The local similarity problem is to determine the similar regions within two given sequences. We recently developed a dynamic programming algorithm for the local similarity problem that requires only space proportional to the sum of the two sequence lengths, whereas earlier methods use space proportional to the product of the lengths. In this paper, we describe how to parallelize the new algorithm and present results of experimental studies on an Intel hypercube. The parallel method provides rapid, high-resolution alignments for users of our software toolkit for pairwise sequence comparison, as illustrated here by a comparison of the chloroplast genomes of tobacco and liverwort.

EnteriX 2003: visualization tools for genome alignments of Enterobacteriaceae

We describe EnteriX, a suite of three web-based visualization tools for graphically portraying alignment information from comparisons among several fixed and user-supplied sequences from related enterobacterial species, anchored on a reference genome (http://bio.cse.psu.edu/). The first visualization, Enteric, displays stacked pairwise alignments between a reference genome and each of the related bacteria, represented schematically as PIPs (Percent Identity Plots). Encoded in the views are large-scale genomic rearrangement events and functional landmarks. The second visualization, Menteric, computes and displays 1 Kb views of nucleotide-level multiple alignments of the sequences, together with annotations of genes, regulatory sites and conserved regions. The third, a Java-based tool named Maj, displays alignment information in two formats, corresponding roughly to the Enteric and Menteric views, and adds zoom-in capabilities. The uses of such tools are diverse, from examining the multiple sequence alignment to infer conserved sites with potential regulatory roles, to scrutinizing the commonalities and differences between the genomes for pathogenicity or phylogenetic studies. The EnteriX suite currently includes >15 enterobacterial genomes, generates views centered on four different anchor genomes and provides support for including user sequences in the alignments.

PipMaker: A World Wide Web Server for Genomic Sequence Alignments

PipMaker is a World‐Wide Web site used to compare two long genomic sequences and identify conserved segments between them. This unit describes the use of the PipMaker server and explains the resulting output files. PipMaker provides an efficient method of aligning genomic sequences and returns a compact, but easy‐to‐interpret form of output, the percent identity plot (pip). For each aligning segment between two sequences the pip shows both the position relative to the first sequence and the degree of similarity. Optional annotations on the pip provide additional information to assist in the interpretation of the alignment. The default parameters of the underlying blastz alignment program are tuned for human‐mouse alignments.

A point of contact between computer science and molecular biology

Molecular biology is rapidly becoming a data-rich science with extensive computational needs. The sheer volume of data poses a serious challenge in storing and retrieving biological information, and the rate of growth is exponential. Linking the heterogeneous data libraries of molecular biology, organizing its diverse and interrelated data sets, and developing effective query options for its databases are all areas for cross-fertilization between molecular biology and computer science. However, even the apparently simple task of analyzing a single sequence of DNA requires complex collaboration. For several years, we have been developing a computer toolkit for analyzing DNA sequences. The biology of gene regulation in mammals has driven the design of the sequence comparison toolkit to emphasize space-efficient algorithms with a high degree of sensitivity and has profoundly affected choice of tools and the development of algorithms. We sketch the biology of this class of problem and show how it specifically drives the software development. The main components of this toolkit are outlined.<<ETX>>

A database for globin gene expression data

We describe a prototype database of sequence alignments and experimental results for the /spl beta/-like globin gene cluster of mammals. This data repository is intended to help the international community of globin gene biologists to plan experiments, to design models and, ultimately, to understand regulation of those genes. Moreover, the approaches and software developed for this project will be applicable to other sequence-analysis problems. Our first steps were to develop a program that can simultaneously align a few very long sequences and to establish an e-mail server that formats any requested portion of the alignment, annotated to indicate highly conserved regions and known run sequence features. We are currently developing a World-Wide Web server that will provide access to the wealth of pertinent experimental data, in register with the annotated alignment, through a variety of query languages and graphical presentations.<<ETX>>