Biomedical subjects

Daniel P Aalberts

Publications and source records attributed to Daniel P Aalberts.

5 recordsLinked to original sources

PubMed2005

Quantifying optimal accuracy of local primary sequence bioinformatics methods.

MOTIVATION: Traditional bioinformatics methods scan primary sequences for local patterns. It is important to assess how accurate local primary sequence methods can be. RESULTS: We study the problem of donor pre-mRNA splice site recognition, where the sequence overlaps between real and decoy datasets can be quantified, exposing the intrinsic limitations of the performance of local primary sequence methods. We assess the accuracy of primary sequence methods generally by studying how they scale with dataset size and demonstrate that our new primary sequence ranking methods have superior performance.

Algorithms↗

PubMed2005

Asymmetry in RNA pseudoknots: observation and theory.

RNA can fold into a topological structure called a pseudoknot, composed of non-nested double-stranded stems connected by single-stranded loops. Our examination of the PseudoBase database of pseudoknotted RNA structures reveals asymmetries in the stem and loop lengths and provocative composition differences between the loops. By taking into account differences between major and minor grooves of the RNA double helix, we explain much of the asymmetry with a simple polymer physics model and statistical mechanical theory, with only one adjustable parameter.

Biopolymers↗

PubMed2004

Efficient computation of optimal oligo-RNA binding.

We present an algorithm that calculates the optimal binding conformation and free energy of two RNA molecules, one or both oligomeric. This algorithm has applications to modeling DNA microarrays, RNA splice-site recognitions and other antisense problems. Although other recent algorithms perform the same calculation in time proportional to the sum of the lengths cubed, O((N1 + N2)3), our oligomer binding algorithm, called bindigo, scales as the product of the sequence lengths, O(N1*N2). The algorithm performs well in practice with the aid of a heuristic for large asymmetric loops. To demonstrate its speed and utility, we use bindigo to investigate the binding proclivities of U1 snRNA to mRNA donor splice sites.

Algorithms↗

PubMed2004

Thermodynamic modeling of donor splice site recognition in pre-mRNA.

When eukaryotic genes are edited by the spliceosome, the first step in intron recognition is the binding of a U1 small nuclear RNA with the donor ( 5(') ) splice site. We model this interaction thermodynamically to identify splice sites. Applied to a set of 65 annotated genes, our "finding with binding" method achieves a significant separation between real and false sites. Analyzing binding patterns allows us to discard a large number of decoy sites. Our results improve statistics-based methods for donor site recognition, demonstrating the promise of physical modeling to find functional elements in the genome.

Base Pairing↗

PubMed2003

Single-strand stacking free energy from DNA beacon kinetics.

DNA beacons are short single-stranded chains which can form closed hairpin shapes through complementary base pairing at their ends. Contrary to the common polymer theory assumption that only their loop length matters, experiments show that their closing kinetics depend on the loop composition. We have modeled the closing kinetics and in so doing have obtained stacking enthalpies and entropies for single-stranded nucleic acids. The resulting change of persistence length with temperature effects the dynamics. With a Monte Carlo study, we answer another polymer question of how the closing time scales with chain length, finding tau approximately N(2.44+/-0.02). There is a significant crossover for shorter chains, bringing the effective exponent into good agreement with experiment.

Biopolymers↗