A fixed-point alignment technique for detection of recurrent and common sequence motifs associated with biological features

A fixed-point alignment analysis technique is presented whichis designed to locate common sequence motifs in collectionsof proteins or nucleic acids. Initially a program aligns a collectionof sequences by a common sequence pattern or known biologicalfeature. The common pattern or feature (fixed-point) may bea user-specified sequence string or a known sequence positionlike mRNA start site, which may be taken directly from the annotatedfeature table of GenBank. Once all alignment markers are located,the sequences are scanned for occurrences of given oligomerswithin a specified span both upstream and downstream of thefixed-point. The occurrences may then be plotted as a functionof the position relative to the fixed-point, displayed as anactual sequence alignment or selectively summarized via variousprogram options. Applications of the technique are discussed. Received on August 17, 1987; accepted on November 17, 1987     

A computational procedure for assessing the significance of RNA secondary structure

In our recent series of papers, we have used the structuresof statistical significance from Monte Carlo simulations toimprove the predictions of secondary structure of RNA and toanalyze the possible role of locally significant structuresin the ljfe cycle of human immunodeficiency virus. Because ofintensive computational requirements for Monte Carlo simulation,it becomes impractical even using a supercomputer to assessthe significance of a structure with a window size > 200along an RNA sequence of 1000 bases or more. In this paper,we have developed a new procedure that drastically reduces thetime needed to assess the significance of structures. In fact,the efficiency of this new method allows us to assess structureson the VAX as well as the CRAY Received on May 11, 1989; accepted on August 22, 1989     

An interactive dot matrix system for locating potentially significant features in nucleic acid molecules

An interactive computer system using a dot matrix approach has been developed and used to determine potentially significant features due to distortions in the B-DNA helix as a result of variations of purine and pyrimidine patterns. Sequences were compared using matrices which were generated using the Calladine-Dickerson rules (C.R. Calladine, J. Mol. Biol. 161, 343-352, 1982 and R.E. Dickerson, J. Mol. Biol. 166, 419-441, 1983). Having control over various parameters to enhance different aspects of the visual appearance of these matrices was helpful in discovering patterns that were not known a priori. Specifically, it was found that a pattern of alternating doublets of purines and pyrimidines appear to exist in regulatory regions. This event is shown to be beyond probabilistic expectation.     

A program for predicting significant RNA secondary structures

We describe a program for the analysis of RNA secondary structure.There are two new features in this program. (i) To get vectorspeeds on a vector pipeline machine (such as Cray X-MP/24) wehave vectorized the secondary structure dynamic algorithm. (ii)The statistical significance of a locally ‘optimal’secondary structure is assessed by a Monte Carlo method. Theresults can be depicted graphically including profiles of thestability of local secondary structures and the distributionof the potentially significant secondary structures in the RNAmolecules. Interesting regions where both the potentially significantsecondary structures and ‘open’ structures (single-strandedcoils) occur can be identified by the plots mentioned above.Furthermore, the speed of the vectorized code allows repeatedMonte Carlo simulations with different overlapping window sizes.Thus, the optimal size of the significant secondary structureoccurring in the interesting region can be assessed by repeatingthe Monte Carlo simulation. The power of the program is demonstratedin the analysis of local secondary structures of human T-celllymphotrophic virus type III (HIV). Received on August 17, 1987; accepted on January 5, 1988     

Proliferation of human B lymphocytes mediated by a soluble factor

Recent studies have established the ability of a proportion of activated human B lymphocytes to undergo G1 phase cell cycle progression and subsequent S phase entry on exposure to factor(s) present in lectin-stimulated mononuclear cell-conditioned media. One factor capable of stimulating activated human B lymphocyte proliferation may be separated from peripheral blood lymphocyte-conditioned media by successive ammonium sulfate precipitation, ion exchange, and gel filtration chromatography. The isolated factor is distinct from the other well-described cytokines, possesses a molecular weight of 12,000-13,000, has a mildly acidic isoelectric point (at pH 6.3-6.6), is protease sensitive, and is relatively heat sensitive. The human B cell mitogenic factor possesses functional and cellular specificity in that its action is restricted to B lymphocytes and its function is proliferative. The production of the B cell mitogenic factor by T lymphocytes is augmented by the presence of a macrophage and further stimulated by syngeneic B cells.