The Human Intermediate Filament Database: comprehensive information on a gene family involved in many human diseases.

We describe a revised and expanded database on human intermediate filament proteins, a major component of the eukaryotic cytoskeleton. The family of 70 intermediate filament genes (including those encoding keratins, desmins, and lamins) is now known to be associated with a wide range of diverse diseases, at least 72 distinct human pathologies, including skin blistering, muscular dystrophy, cardiomyopathy, premature aging syndromes, neurodegenerative disorders, and cataract. To date, the database catalogs 1,274 manually-curated pathogenic sequence variants and 170 allelic variants in intermediate filament genes from over 459 peer-reviewed research articles. Unrelated cases were collected from all of the six sequence homology groups and the sequence variations were described at cDNA and protein levels with links to the related diseases and reference articles. The mutations and polymorphisms are presented in parallel with data on protein structure, gene, and chromosomal location and basic information on associated diseases. Detailed statistics relating to the variants records in the database are displayed by homology group, mutation type, affected domain, associated diseases, and nucleic and amino acid substitutions. Multiple sequence alignment algorithms can be run from queries to determine DNA or protein sequence conservation. Literature sources can be interrogated within the database and external links are provided to public databases. The database is freely and publicly accessible online at www.interfil.org (last accessed 13 September 2007). Users can query the database by various keywords and the search results can be downloaded. It is anticipated that the Human Intermediate Filament Database (HIFD) will provide a useful resource to study human genome variations for basic scientists, clinicians, and students alike.

Use and Misuse of Laplace's Law in Ophthalmology.

PURPOSE: Laplace's Law, with its compactness and simplicity, has long been employed in ophthalmology for describing the mechanics of the corneoscleral shell. We questioned the appropriateness of Laplace's Law for computing wall stress in the eye considering the advances in knowledge of ocular biomechanics. METHODS: In this manuscript we recapitulate the formulation of Laplace's Law, as well as common interpretations and uses in ophthalmology. Using numerical modeling, we study how Laplace's Law cannot account for important characteristics of the eye, such as variations in globe shape and size or tissue thickness, anisotropy, viscoelasticity, or that the eye is a living, dynamic organ. RESULTS: We show that accounting for various geometrical and material factors, excluded from Laplace's Law, can alter estimates of corneoscleral wall stress as much as 456% and, therefore, that Laplace's Law is unreliable. CONCLUSIONS: We conclude by illustrating how computational techniques, such as finite element modeling, can account for the factors mentioned above, and are thus more suitable tools to provide quantitative characterization of corneoscleral biomechanics.

Enhancement of Corneal Visibility in Optical Coherence Tomography Images with Corneal Opacification.

PURPOSE: To establish and to rank the performance of a corneal adaptive compensation (CAC) algorithm in enhancing corneal images with scars acquired from three commercially available anterior segment optical coherence tomography (ASOCT) devices. METHODS: Horizontal B-scans of the cornea were acquired from 10 patients using three ASOCT devices (Spectralis, RTVue, and Cirrus). We compared ASOCT image quality (with and without CAC) by computing the intralayer contrast (a measure of shadow removal), the interlayer contrast (a measure of tissue boundary visibility), and the tissue/background contrast (a measure of overall corneal visibility). All six groups (Spectralis, RTVue, Cirrus, Spectralis+CAC, RTVue+CAC, and Cirrus+CAC) were ranked according to a global performance index that averaged all contrast quantities. RESULTS: CAC provided mean intralayer contrasts improvement for all devices (all P < 0.05). Mean tissue/boundary contrasts were also improved for Spectralis and Cirrus (both P < 0.001). Mean interlayer contrasts were increased for Spectralis (P = 0.011) only. When comparing global performance indices, all CAC groups outperformed their corresponding baseline groups significantly. RTVue performed best without CAC, but Spectralis+CAC was ranked first. CONCLUSIONS: ASOCT images of corneal scars may be enhanced by CAC through shadow removal, improved tissue boundary visibility, and enhanced corneal visibility against the image background. RTVue produces the finest baseline images but the best image quality can be achieved by applying CAC to Spectralis images. TRANSLATIONAL RELEVANCE: CAC could enhance visibility of corneal images with scars acquired from commercially available ASOCT devices and could aid preoperative planning of patients for ophthalmic procedures.

Enhancement of Corneal Visibility in Optical Coherence Tomography Images Using Corneal Adaptive Compensation.

PURPOSE: To improve the contrast of optical coherence tomography (OCT) images of the cornea (post processing). METHODS: We have recently developed standard compensation (SC) algorithms to remove light attenuation artifacts. A more recent approach, namely adaptive compensation (AC), further limited noise overamplification within deep tissue regions. AC was shown to work efficiently when all A-scan signals were fully attenuated at high depth. But in many imaging applications (e.g., OCT imaging of the cornea), such an assumption is not satisfied, which can result in strong noise overamplification. A corneal adaptive compensation (CAC) algorithm was therefore developed to overcome such limitation. CAC benefited from local A-scan processing (rather than global as in AC) and its performance was compared with that of SC and AC using Fourier-domain OCT images of four human corneas. RESULTS: CAC provided considerably superior image contrast improvement than SC or AC did, with excellent visibility of the corneal stroma, low noise overamplification, homogeneous signal amplification, and high contrast. Specifically, CAC provided mean interlayer contrasts (a measure of high stromal visibility and low noise) greater than 0.97, while SC and AC provided lower values ranging from 0.38 to 1.00. CONCLUSION: CAC provided considerable improvement compared with SC and AC by eliminating noise overamplification, while maintaining all benefits of compensation, thus making the corneal endothelium and corneal thickness easily identifiable. TRANSLATIONAL RELEVANCE: CAC may find wide applicability in clinical practice and could contribute to improved morphometric and biomechanical understanding of the cornea.

In silico analysis of p53 using the p53 knowledgebase: mutations, polymorphisms, microRNAs and pathways.

P53 is probably the most important tumor suppressor known. Over the years, information about this gene has increased dramatically. We have built a comprehensive knowledgebase of p53, which aims to facilitate wet-lab biologists to formulate their experiments and new-comers to learn whatever they need about the gene and bioinformaticians to make new discoveries through data analysis. Using the information curated, including mutation information, transcription factors, transcriptional targets, and single nucleotide polymorphisms, we have performed extensive bioinformatics analysis, and made several new discoveries about p53. We have identified point missense mutations that are over-represented in cancers, but lack of functional studies. By assessing the capability of six p53 transcriptional targets' tag SNPs selected from HapMap to capture SNPs obtained from National Institute of Environmental Health Sciences (NIEHS) Environmental Genome project and vice versa, we conclude that NIEHS data is a better source for tagSNP selections of these genes in future association studies. Analysis of microRNA regulation in the transcriptional network of the p53 gene reveals potentially important regulatory relationships between oncogenic microRNAs and transcription factors of p53. By mapping transcription factors of p53 to pathways involved in cell cycle and apoptosis, we have identified distinctive transcriptional controls of p53 in these two physiological states.

Gastric Cancer (Biomarkers) Knowledgebase (GCBKB): A Curated and Fully Integrated Knowledgebase of Putative Biomarkers Related to Gastric Cancer.

The Gastric Cancer (Biomarkers) Knowledgebase (GCBKB) (http://biomarkers.bii.a-star.edu.sg/background/gastricCancerBiomarkersKb.php) is a curated and fully integrated knowledgebase that provides data relating to putative biomarkers that may be used in the diagnosis and prognosis of gastric cancer. It is freely available to all users. The data contained in the knowledgebase was derived from a large literature source and the putative biomarkers therein have been annotated with data from the public domain. The knowledgebase is maintained by a curation team who update the data from a defined source. As well as mining data from the literature, the knowledgebase will also be populated with unpublished experimental data from investigators working in the gastric cancer biomarker discovery field. Users can perform searches to identify potential markers defined by experiment type, tissue type and disease state. Search results may be saved, manipulated and retrieved at a later date. As far as the authors are aware this is the first open access database dedicated to the discovery and investigation of gastric cancer biomarkers.