SUMMARY: The DNA in eukaryotic cells is packed into the chromatin that is composed of nucleosomes. Positioning of the nucleosome core particles on the sequence is a problem of great interest because of the role nucleosomes play in different cellular processes including gene regulation. Using the sequence structure of 10.4 base DNA repeat presented in our previous works and nucleosome core DNA sequences database, we have derived the complete nucleosome DNA bendability matrix of Caenorhabditis elegans. We have developed a web server named FineStr that allows users to upload genomic sequences in FASTA format and to perform a single-base-resolution nucleosome mapping on them. AVAILABILITY: FineStr server is freely available for use on the web at http:/www.cs.bgu.ac.il/ approximately nucleom. The site contains a help file with explanation regarding the exact usage. CONTACT: [email protected].

Nucleotide and amino acid sequences carry many different codes, patterns recognized by numerous different reading devices. To name a few: THE triplet code, gene splicing code, translation framing code, chromatin code. One very basic property of the codes is their overlapping, so that one and the same character in given position of given sequence is involved simultaneously in several different messages. Progress in elucidation of the chromatin code will be reported. A newly discovered proteomic code of protein sequences will be discussed. It is based on the universal loop fold structure of globular proteins. The abundant standard size closed loops, 25-35 amino-acid residues, apparently, represent descendants of the ancestral closed loops, each with its specific sequence and structure. The evolution of the triplet code and early evolution of proteins will be outlined.

This review is a brief outline of the chronology and essence of early events in bioinformatics, covering the period from 1869 (discovery of DNA by Miescher) to 1980-1981 (beginning of massive sequencing). For the purpose of this review, bioinformatics is understood as a chapter of molecular biology dealing with the amino acid and nucleotide sequences and with the information they carry.

MOTIVATION: Completely sequenced genomes allow for detection and analysis of the relatively weak periodicities of 10-11 basepairs (bp). Two sources contribute to such signals: correlations in the corresponding protein sequences due to the amphipatic character of alpha-helices and the folding of DNA (nucleosomal patterns, DNA supercoiling). Since the topological state of genomic DNA is of importance for its replication, recombination and transcription, there is an immediate interest to obtain information about the supercoiled state from sequence periodicities. RESULTS: We show that correlations within proteins affect mainly the oscillations at distances below 35 bp. The long-ranging correlations up to 100 bp reflect primarily DNA folding. For the yeast genome these oscillations are consistent in detail with the chromatin structure. For eubacteria and archaea the periods deviate significantly from the 10.55 bp value for free DNA. These deviations suggest that while a period of 11 bp in bacteria reflects negative supercoiling, the significantly different period of thermophilic archaea close to 10 bp corresponds to positive supercoiling of thermophilic archaeal genomes. AVAILABILITY: Protein sets and C programs for the calculation of correlation functions are available on request from the authors (see http://itb.biologie.hu-berlin.de).

MOTIVATION: A nucleosome DNA positioning pattern is known to be one of the weakest (highly degenerated) patterns. The alignment procedure that has been developed recently for the extraction of such a pattern is based on a statistical matching of the sequences, and its success depends on the pattern/background ratio in the individual sequences and in the generated pattern. The heuristic nature of the method and distinctive properties of the pattern bring up the question of efficiency and sensitivity in the procedure. This paper presents a method of verification for this multiple sequence alignment algorithm. RESULTS: To verify the applicability of the multiple alignment approach, we constructed a set of sequences carrying the hidden pattern. The pattern was presented by weak ('signal') oscillations of occurrences of AA and TT dinucleotides along otherwise random sequences. Only a few dinucleotides of any given 145 base long sequence would correspond to the signal, appearing in about the same phase within the simulated periodic pattern. The novelty of our simulation approach is that we simulated a database as a whole, as opposed to simulating each sequence separately. The correlation between the hidden pattern and a sequence from the database is negligible on average, but our statistical multicycle alignment procedure produced the pattern with attributes very close to the simulated ones. The accuracy of the procedure was tested and calibrated. The presence in a typical sequence of as little as three dinucleotides corresponding to the signal is sufficient to generate (detect) the pattern hidden in a collection of 204 sequences.

MOTIVATION: Although one would normally expect a given regulatory element to perform best when it fully matches its consensus sequence, this is generally far from being the case. Usually, almost none of the actual sites fits the consensus exactly, and some of those that do fit do not perform well. The main reason for that is the very nature of the sequences and the messages (codes) they contain. Normally, any given stretch of the sequence with one or another regulatory site not only carries this regulatory message, but several more messages of various types as well. These messages overlap with the regulatory element in such a way that the letter (base) which actually appears in any given sequence position simultaneously belongs to one or more additional codes. Apart from numerous individual codes (sequence patterns) specific for a given species or gene, there are many different general (universal) sequence codes all interacting with one another. These are the classical triplet code, DNA shape code, chromatin code, gene splicing code, modulation code and many more, including those that have not yet been discovered. Examples of overlapping of different codes and their interaction are discussed, as well as the role of degeneracy of the codes and the sequence complexity as a function of code density.

Software is presented to plot the sequence-dependent spatial trajectory of the DNA double helix and/or distribution of curvature along the DNA molecule. The nearest-neighbor wedge model is implemented to calculate overall DNA path using local helix parameters: helix twist angle, wedge (deflection) angle and direction (of deflection) angle. The procedures described proved to be very convenient as tools for investigation of a relationship between overall DNA curvature and its gel electrophoretic mobility. All parameters of the model had been estimated from experimental data. Using these wedge parameters the program takes, as input, any DNA sequence and calculates the likely degree of curvature at each point along the molecule. This information is displayed both graphically and in the form of simplified representations of curved double helices. The Software, CURVATURE, can thus be used to investigate possible roles of curvature in modulation of gene expression and for location of curved portions of DNA, which may play an important role in sequence-specific protein--DNA interactions.