Free energy estimation of short DNA duplex hybridizations

<p>Abstract</p> <p>Background</p> <p>Estimation of DNA duplex hybridization free energy is widely used for predicting cross-hybridizations in DNA computing and microarray experiments. A number of software programs based on different methods and parametrizations are available for the theoretical estimation of duplex free energies. However, significant differences in free energy values are sometimes observed among estimations obtained with various methods, thus being difficult to decide what value is the accurate one.</p> <p>Results</p> <p>We present in this study a quantitative comparison of the similarities and differences among four published DNA/DNA duplex free energy calculation methods and an extended Nearest-Neighbour Model for perfect matches based on triplet interactions. The comparison was performed on a benchmark data set with 695 pairs of short oligos that we collected and manually curated from 29 publications. Sequence lengths range from 4 to 30 nucleotides and span a large GC-content percentage range. For perfect matches, we propose an extension of the Nearest-Neighbour Model that matches or exceeds the performance of the existing ones, both in terms of correlations and root mean squared errors. The proposed model was trained on experimental data with temperature, sodium and sequence concentration characteristics that span a wide range of values, thus conferring the model a higher power of generalization when used for free energy estimations of DNA duplexes under non-standard experimental conditions.</p> <p>Conclusions</p> <p>Based on our preliminary results, we conclude that no statistically significant differences exist among free energy approximations obtained with 4 publicly available and widely used programs, when benchmarked against a collection of 695 pairs of short oligos collected and curated by the authors of this work based on 29 publications. The extended Nearest-Neighbour Model based on triplet interactions presented in this work is capable of performing accurate estimations of free energies for perfect match duplexes under both standard and non-standard experimental conditions and may serve as a baseline for further developments in this area of research.</p

RNAstructure: software for RNA secondary structure prediction and analysis

<p>Abstract</p> <p>Background</p> <p>To understand an RNA sequence's mechanism of action, the structure must be known. Furthermore, target RNA structure is an important consideration in the design of small interfering RNAs and antisense DNA oligonucleotides. RNA secondary structure prediction, using thermodynamics, can be used to develop hypotheses about the structure of an RNA sequence.</p> <p>Results</p> <p>RNAstructure is a software package for RNA secondary structure prediction and analysis. It uses thermodynamics and utilizes the most recent set of nearest neighbor parameters from the Turner group. It includes methods for secondary structure prediction (using several algorithms), prediction of base pair probabilities, bimolecular structure prediction, and prediction of a structure common to two sequences. This contribution describes new extensions to the package, including a library of C++ classes for incorporation into other programs, a user-friendly graphical user interface written in JAVA, and new Unix-style text interfaces. The original graphical user interface for Microsoft Windows is still maintained.</p> <p>Conclusion</p> <p>The extensions to RNAstructure serve to make RNA secondary structure prediction user-friendly. The package is available for download from the Mathews lab homepage at <url>http://rna.urmc.rochester.edu/RNAstructure.html</url>.</p

Granulomatosis with Polyangiitis as a Cause of Sudden-Onset Bilateral Sensorineural Hearing Loss: Case Report and Recommendations for Initial Assessment

Granulomatosis with polyangiitis (GPA) is a severe systemic vasculitis that commonly affects the paranasal sinuses, upper and lower respiratory tracts, and kidneys. GPA has also been associated with sensorineural hearing loss (SNHL), through inflammation of the cochlear apparatus. Early recognition, diagnostic laboratory evaluation, and appropriate treatment are essential to improve outcomes and achieve remission for patients with GPA. Here, we present a case of bilateral sudden sensorineural hearing loss (SSNHL) and distal symmetric polyneuropathy as the first presenting signs of GPA. A specific diagnostic work-up to rule out autoimmune inner-ear disease in patients with bilateral SSNHL is not clearly stated in the clinical practice guidelines from the American Academy of Otolaryngology-Head and Neck Surgery. The aim of this paper is to delineate an appropriate diagnostic work-up for patients with bilateral SSNHL when there is concern for autoimmune disease

Granulomatosis with Polyangiitis as a Cause of Sudden-Onset Bilateral Sensorineural Hearing Loss: Case Report and Recommendations for Initial Assessment

Granulomatosis with polyangiitis (GPA) is a severe systemic vasculitis that commonly affects the paranasal sinuses, upper and lower respiratory tracts, and kidneys. GPA has also been associated with sensorineural hearing loss (SNHL), through inflammation of the cochlear apparatus. Early recognition, diagnostic laboratory evaluation, and appropriate treatment are essential to improve outcomes and achieve remission for patients with GPA. Here, we present a case of bilateral sudden sensorineural hearing loss (SSNHL) and distal symmetric polyneuropathy as the first presenting signs of GPA. A specific diagnostic work-up to rule out autoimmune inner-ear disease in patients with bilateral SSNHL is not clearly stated in the clinical practice guidelines from the American Academy of Otolaryngology-Head and Neck Surgery. The aim of this paper is to delineate an appropriate diagnostic work-up for patients with bilateral SSNHL when there is concern for autoimmune disease.</jats:p