Definition of an automated Content-Based Image Retrieval (CBIR) system for the comparison of dermoscopic images of pigmented skin lesions

Background  

New generations of image-based diagnostic machines are based on digital technologies for data acquisition; consequently, the diffusion of digital archiving systems for diagnostic exams preservation and cataloguing is rapidly increasing. To overcome the limits of current state of art text-based access methods, we have developed a novel content-based search engine for dermoscopic images to support clinical decision making.     

Parameter estimation in systems biology models using spline approximation

Background  

Mathematical models for revealing the dynamics and interactions properties of biological systems play an important role in computational systems biology. The inference of model parameter values from time-course data can be considered as a "reverse engineering" process and is still one of the most challenging tasks. Many parameter estimation methods have been developed but none of these methods is effective for all cases and can overwhelm all other approaches. Instead, various methods have their advantages and disadvantages. It is worth to develop parameter estimation methods which are robust against noise, efficient in computation and flexible enough to meet different constraints.     

The contributions of interlocking loops and extensive nonlinearity to the properties of circadian clock models

Background

Sensitivity and robustness are essential properties of circadian clock systems, enabling them to respond to the environment but resist noisy variations. These properties should be recapitulated in computational models of the circadian clock. Highly nonlinear kinetics and multiple loops are often incorporated into models to match experimental time-series data, but these also impact on model properties for clock models.

Methodology/Principal Findings

Here, we study the consequences of complicated structure and nonlinearity using simple Goodwin-type oscillators and the complex Arabidopsis circadian clock models. Sensitivity analysis of the simple oscillators implies that an interlocked multi-loop structure reinforces sensitivity/robustness properties, enhancing the response to external and internal variations. Furthermore, we found that reducing the degree of nonlinearity could sometimes enhance the robustness of models, implying that ad hoc incorporation of nonlinearity could be detrimental to a model''s perceived credibility.

Conclusion

The correct multi-loop structure and degree of nonlinearity are therefore critical in contributing to the desired properties of a model as well as its capacity to match experimental data.     

Evaluation of the structural quality of modeled proteins by using globularity criteria

Background  

The knowledge of the three-dimensional structure of globular proteins is fundamental for a detailed investigation of their functional properties. Experimental methods are too slow for structure investigation on a large scale, while computational prediction methods offer alternatives that are continuously being improved. The international Comparative Assessment of Structure Prediction (CASP), an "a posteriori" evaluation of the quality of theoretical models when the experimental structure becomes available, demonstrates that predictions can be successful as well as unsuccessful, and this suggests the necessity for evaluations able to discard "a priori" the wrong models.     

The cosmological model of eternal inflation and the transition from chance to biological evolution in the history of life

Background  

Recent developments in cosmology radically change the conception of the universe as well as the very notions of "probable" and "possible". The model of eternal inflation implies that all macroscopic histories permitted by laws of physics are repeated an infinite number of times in the infinite multiverse. In contrast to the traditional cosmological models of a single, finite universe, this worldview provides for the origin of an infinite number of complex systems by chance, even as the probability of complexity emerging in any given region of the multiverse is extremely low. This change in perspective has profound implications for the history of any phenomenon, and life on earth cannot be an exception.     

A framework for evolutionary systems biology

Background  

Many difficult problems in evolutionary genomics are related to mutations that have weak effects on fitness, as the consequences of mutations with large effects are often simple to predict. Current systems biology has accumulated much data on mutations with large effects and can predict the properties of knockout mutants in some systems. However experimental methods are too insensitive to observe small effects.     

LitMiner: integration of library services within a bio-informatics application

Background

This paper examines how the adoption of a subject-specific library service has changed the way in which its users interact with a digital library. The LitMiner text-analysis application was developed to enable biologists to explore gene relationships in the published literature. The application features a suite of interfaces that enable users to search PubMed as well as local databases, to view document abstracts, to filter terms, to select gene name aliases, and to visualize the co-occurrences of genes in the literature. At each of these stages, LitMiner offers the functionality of a digital library. Documents that are accessible online are identified by an icon. Users can also order documents from their institution's library collection from within the application. In so doing, LitMiner aims to integrate digital library services into the research process of its users.

Methods

Case study

Results

This integration of digital library services into the research process of biologists results in increased access to the published literature.

Conclusion

In order to make better use of their collections, digital libraries should customize their services to suit the research needs of their patrons.

     

Determining the fate of selenium in wheat biofortification: an isotopically labelled field trial study

Background and aims

Root hair growth and development are important features of plant response to varying soil conditions and of nutrient and water uptake. Most current methods of characterizing root hairs in the field are unreliable or inefficient. We describe a method to quantify root hair area in digital images, such as those collected in situ by minirhizotron systems.

Methods

This method uses ImageJ and R open source software and is partially automated using code presented here. It requires manual tracing of a subset of root hair images (training data set) to which a multivariate logistic regression is fit with each color channel in the image as an independent variable. Thereafter the model is applied to complete sets of selected root hair sections to estimate total root hair area.

Results

There was good agreement between the training data sets and the predictions of the regression models in castor (Ricinus communis L.), maize (Zea mays L.), and papaya (Carica papaya L.).

Conclusion

This method enables time-efficient and consistent quantification of root hairs using in situ root imaging systems that are already widely in use.

     

Snazer: the simulations and networks analyzer

Background  

Networks are widely recognized as key determinants of structure and function in systems that span the biological, physical, and social sciences. They are static pictures of the interactions among the components of complex systems. Often, much effort is required to identify networks as part of particular patterns as well as to visualize and interpret them.     

Using ESTs to improve the accuracy of de novo gene prediction

Background  

ESTs are a tremendous resource for determining the exon-intron structures of genes, but even extensive EST sequencing tends to leave many exons and genes untouched. Gene prediction systems based exclusively on EST alignments miss these exons and genes, leading to poor sensitivity. De novo gene prediction systems, which ignore ESTs in favor of genomic sequence, can predict such "untouched" exons, but they are less accurate when predicting exons to which ESTs align. TWINSCAN is the most accurate de novo gene finder available for nematodes and N-SCAN is the most accurate for mammals, as measured by exact CDS gene prediction and exact exon prediction.     

The molecular portrait of in vitro growth by meta-analysis of gene-expression profiles

Background  

Cell lines as model systems of tumors and tissues are essential in molecular biology, although they only approximate the properties of in vivo cells in tissues. Cell lines have been selected under in vitro conditions for a long period of time, affecting many specific cellular pathways and processes.     

Exploring biological network structure with clustered random networks

Background  

Complex biological systems are often modeled as networks of interacting units. Networks of biochemical interactions among proteins, epidemiological contacts among hosts, and trophic interactions in ecosystems, to name a few, have provided useful insights into the dynamical processes that shape and traverse these systems. The degrees of nodes (numbers of interactions) and the extent of clustering (the tendency for a set of three nodes to be interconnected) are two of many well-studied network properties that can fundamentally shape a system. Disentangling the interdependent effects of the various network properties, however, can be difficult. Simple network models can help us quantify the structure of empirical networked systems and understand the impact of various topological properties on dynamics.     

Color standardization and optimization in Whole Slide Imaging

Introduction

Standardization and validation of the color displayed by digital slides is an important aspect of digital pathology implementation. While the most common reason for color variation is the variance in the protocols and practices in the histology lab, the color displayed can also be affected by variation in capture parameters (for example, illumination and filters), image processing and display factors in the digital systems themselves.

Method

We have been developing techniques for color validation and optimization along two paths. The first was based on two standard slides that are scanned and displayed by the imaging system in question. In this approach, one slide is embedded with nine filters with colors selected especially for H&;E stained slides (looking like tiny Macbeth color chart); the specific color of the nine filters were determined in our previous study and modified for whole slide imaging (WSI). The other slide is an H&;E stained mouse embryo. Both of these slides were scanned and the displayed images were compared to a standard. The second approach was based on our previous multispectral imaging research.

Discussion

As a first step, the two slide method (above) was used to identify inaccurate display of color and its cause, and to understand the importance of accurate color in digital pathology. We have also improved the multispectral-based algorithm for more consistent results in stain standardization. In near future, the results of the two slide and multispectral techniques can be combined and will be widely available.We have been conducting a series of researches and developing projects to improve image quality to establish Image Quality Standardization. This paper discusses one of most important aspects of image quality – color.

     

GEM System: automatic prototyping of cell-wide metabolic pathway models from genomes

Background  

Successful realization of a "systems biology" approach to analyzing cells is a grand challenge for our understanding of life. However, current modeling approaches to cell simulation are labor-intensive, manual affairs, and therefore constitute a major bottleneck in the evolution of computational cell biology.     

Anatomical evaluation of CT-MRI combined femoral model

Background

Breast density is a significant breast cancer risk factor. Currently, there is no standard method for measuring this important factor. Work presented here represents an essential component of an ongoing project that seeks to determine the appropriate method for calibrating (standardizing) mammography image data to account for the x-ray image acquisition influences. Longer term goals of this project are to make accurate breast density measurements in support of risk studies.

Methods

Logarithmic response calibration curves and effective x-ray attenuation coefficients were measured from two full field digital mammography (FFDM) systems with breast tissue equivalent phantom imaging and compared. Normalization methods were studied to assess the possibility of reducing the amount of calibration data collection. The percent glandular calibration map functional form was investigated. Spatial variations in the calibration data were used to assess the uncertainty in the calibration application by applying error propagation analyses.

Results

Logarithmic response curves are well approximated as linear. Measured effective x-ray attenuation coefficients are characteristic quantities independent of the imaging system and are in agreement with those predicted numerically. Calibration data collection can be reduced by applying a simple normalization technique. The calibration map is well approximated as linear. Intrasystem calibration variation was on the order of four percent, which was approximately half of the intersystem variation.

Conclusion

FFDM systems provide a quantitative output, and the calibration quantities presented here may be used for data acquired on similar FFDM systems.     

Identification of surgically-induced longitudinal lesions of the equine deep digital flexor tendon in the digital flexor tendon sheath using contrast-enhanced ultrasonography: an <Emphasis Type="Italic">ex-vivo</Emphasis> pilot study

Background

Longitudinal tears in the lateral aspect of the deep digital flexor tendon are the most common causes of pain localised to the equine digital flexor tendon sheath. However conventional ultrasonographic techniques provide limited information about acute lesions. Ultrasonographic contrast agents are newly developed materials that have contributed to advancement in human diagnostic imaging. They are currently approved for intravenous use in human and animal models. In this study we described intrathecal use in the horse. This study was undertaken to evaluate the reliability of standard and angle contrast-enhanced ultrasonography to detect and characterize surgically-induced longitudinal lesions in the deep digital flexor tendons.In this pilot study surgically-induced lesions were created in the lateral aspect of the deep digital flexor tendon within the digital flexor tendon sheath in 10 isolated equine limbs to generate a replicable model for naturally occurring lesions. Another 10 specimens were sham operated. All the limbs were examined ultrasonographically before and shortly after the intrasynovial injection of an ultrasound contrast agent containing stabilised microbubbles. The images were blindly evaluated to detect the ability to identify surgically-created lesions. The deep digital flexor tendons were dissected and a series of slices were obtained. The depth of longitudinal defects identified with contrast-enhanced ultrasound scans was compared to the real extent of the lesions measured in the corresponding gross tendon sections.

Results

Contrast-enhanced ultrasonography with both angle and standard approach provided a significant higher proportion of correct diagnoses compared to standard and angle contrast ultrasonography (p < 0.01). Contrast-enhanced ultrasonography reliably estimated the depth of surgically-induced longitudinal lesions in the deep digital flexor tendons.

Conclusion

Contrast-enhanced ultrasound of the digital flexor tendon sheath could be an effective tool to detect intrasynovial longitudinal tears of the deep digital flexor tendon, although an in vivo study is required to confirm these results for naturally occurring lesions.

     

NET: a new framework for the vectorization and examination of network data

Background

The analysis of complex networks both in general and in particular as pertaining to real biological systems has been the focus of intense scientific attention in the past and present. In this paper we introduce two tools that provide fast and efficient means for the processing and quantification of biological networks like Drosophila tracheoles or leaf venation patterns: the Network Extraction Tool (NET) to extract data and the Graph-edit-GUI (GeGUI) to visualize and modify networks.

Results

NET is especially designed for high-throughput semi-automated analysis of biological datasets containing digital images of networks. The framework starts with the segmentation of the image and then proceeds to vectorization using methodologies from optical character recognition. After a series of steps to clean and improve the quality of the extracted data the framework produces a graph in which the network is represented only by its nodes and neighborhood-relations. The final output contains information about the adjacency matrix of the graph, the width of the edges and the positions of the nodes in space. NET also provides tools for statistical analysis of the network properties, such as the number of nodes or total network length. Other, more complex metrics can be calculated by importing the vectorized network to specialized network analysis packages. GeGUI is designed to facilitate manual correction of non-planar networks as these may contain artifacts or spurious junctions due to branches crossing each other. It is tailored for but not limited to the processing of networks from microscopy images of Drosophila tracheoles.

Conclusion

The networks extracted by NET closely approximate the network depicted in the original image. NET is fast, yields reproducible results and is able to capture the full geometry of the network, including curved branches. Additionally GeGUI allows easy handling and visualization of the networks.

     

Single-molecule imaging and manipulation of biomolecular machines and systems

Background

Biological molecular machines support various activities and behaviors of cells, such as energy production, signal transduction, growth, differentiation, and migration.