Arbitration in International Commercial Agreements: The Noose Draws Tighter

WOS: 000298822100014PubMed ID: 22166511This study aimed to examine fibroblast growth factor-19 (FGF-19) in type 2 diabetic (T2DM) patients with metabolic syndrome (MetS) and to evaluate the relationship between FGF-19 and other cardiovascular risk factors, such as atherogenic index of plasma (AIP) and hsCRP. 26 T2DM patients with MetS and 12 healthy controls were enrolled in the study. Serum FGF-19 levels were measured by sandwich ELISA, and compared with other cardiovascular risk factors; lipid profile, AIP, glucose, HbA1c, and hsCRP. AIP was calculated as log (TG/HDL-c). The median (1-3.quartile) FGF-19 levels in T2DM patients with MetS and healthy controls were 122.90 (108.63-237.60) pg/ml and 293.45 (153.64-370.31) pg/ml, respectively (P=0.003). Patients were also grouped by body mass index (BMI) = 30 kg/m(2) (n=13) with median (1-3.quartile) FGF-19 values 168.70 (113.54-275.77) pg/mL and 115.89 (97.94-200.40) pg/mL, respectively (P=0.007). Significant negative correlations were found between FGF-19 and BMI, triglyceride, log (TG/HDL-c), hsCRP, and HbA1c (r=-0.526, P=0.001; r=-0.327, P=0.05; r=-0.312, P=0.05; r=-0.435, P=0.006; r=-0.357, P=0.028, respectively). We showed that FGF-19 levels are low in T2DM patients with MerS. The negative relationship between FGF-19 and several known cardiovascular risk factors such as TG, log (TG/HDL-c), hsCRP and HbA1c in diabetic patients with MetS suggests that FGF-19 can be used as a contributing marker

Multi-Instance Multi-Label Learning

In this paper, we propose the MIML (Multi-Instance Multi-Label learning) framework where an example is described by multiple instances and associated with multiple class labels. Compared to traditional learning frameworks, the MIML framework is more convenient and natural for representing complicated objects which have multiple semantic meanings. To learn from MIML examples, we propose the MimlBoost and MimlSvm algorithms based on a simple degeneration strategy, and experiments show that solving problems involving complicated objects with multiple semantic meanings in the MIML framework can lead to good performance. Considering that the degeneration process may lose information, we propose the D-MimlSvm algorithm which tackles MIML problems directly in a regularization framework. Moreover, we show that even when we do not have access to the real objects and thus cannot capture more information from real objects by using the MIML representation, MIML is still useful. We propose the InsDif and SubCod algorithms. InsDif works by transforming single-instances into the MIML representation for learning, while SubCod works by transforming single-label examples into the MIML representation for learning. Experiments show that in some tasks they are able to achieve better performance than learning the single-instances or single-label examples directly.Comment: 64 pages, 10 figures; Artificial Intelligence, 201

Aneuploidy prediction and tumor classification with heterogeneous hidden conditional random fields

Motivation: The heterogeneity of cancer cannot always be recognized by tumor morphology, but may be reflected by the underlying genetic aberrations. Array comparative genome hybridization (array-CGH) methods provide high-throughput data on genetic copy numbers, but determining the clinically relevant copy number changes remains a challenge. Conventional classification methods for linking recurrent alterations to clinical outcome ignore sequential correlations in selecting relevant features. Conversely, existing sequence classification methods can only model overall copy number instability, without regard to any particular position in the genome

Gene Function Classification Using Bayesian Models with Hierarchy-Based Priors

We investigate the application of hierarchical classification schemes to the annotation of gene function based on several characteristics of protein sequences including phylogenic descriptors, sequence based attributes, and predicted secondary structure. We discuss three Bayesian models and compare their performance in terms of predictive accuracy. These models are the ordinary multinomial logit (MNL) model, a hierarchical model based on a set of nested MNL models, and a MNL model with a prior that introduces correlations between the parameters for classes that are nearby in the hierarchy. We also provide a new scheme for combining different sources of information. We use these models to predict the functional class of Open Reading Frames (ORFs) from the E. coli genome. The results from all three models show substantial improvement over previous methods, which were based on the C5 algorithm. The MNL model using a prior based on the hierarchy outperforms both the non-hierarchical MNL model and the nested MNL model. In contrast to previous attempts at combining these sources of information, our approach results in a higher accuracy rate when compared to models that use each data source alone. Together, these results show that gene function can be predicted with higher accuracy than previously achieved, using Bayesian models that incorporate suitable prior information

Multi-Target Prediction: A Unifying View on Problems and Methods

Multi-target prediction (MTP) is concerned with the simultaneous prediction of multiple target variables of diverse type. Due to its enormous application potential, it has developed into an active and rapidly expanding research field that combines several subfields of machine learning, including multivariate regression, multi-label classification, multi-task learning, dyadic prediction, zero-shot learning, network inference, and matrix completion. In this paper, we present a unifying view on MTP problems and methods. First, we formally discuss commonalities and differences between existing MTP problems. To this end, we introduce a general framework that covers the above subfields as special cases. As a second contribution, we provide a structured overview of MTP methods. This is accomplished by identifying a number of key properties, which distinguish such methods and determine their suitability for different types of problems. Finally, we also discuss a few challenges for future research

Incorporating functional inter-relationships into protein function prediction algorithms

<p>Abstract</p> <p>Background</p> <p>Functional classification schemes (e.g. the Gene Ontology) that serve as the basis for annotation efforts in several organisms are often the source of gold standard information for computational efforts at supervised protein function prediction. While successful function prediction algorithms have been developed, few previous efforts have utilized more than the protein-to-functional class label information provided by such knowledge bases. For instance, the Gene Ontology not only captures protein annotations to a set of functional classes, but it also arranges these classes in a DAG-based hierarchy that captures rich inter-relationships between different classes. These inter-relationships present both opportunities, such as the potential for additional training examples for small classes from larger related classes, and challenges, such as a harder to learn distinction between similar GO terms, for standard classification-based approaches.</p> <p>Results</p> <p>We propose a method to enhance the performance of classification-based protein function prediction algorithms by addressing the issue of using these interrelationships between functional classes constituting functional classification schemes. Using a standard measure for evaluating the semantic similarity between nodes in an ontology, we quantify and incorporate these inter-relationships into the <it>k</it>-nearest neighbor classifier. We present experiments on several large genomic data sets, each of which is used for the modeling and prediction of over hundred classes from the GO Biological Process ontology. The results show that this incorporation produces more accurate predictions for a large number of the functional classes considered, and also that the classes benefitted most by this approach are those containing the fewest members. In addition, we show how our proposed framework can be used for integrating information from the entire GO hierarchy for improving the accuracy of predictions made over a set of base classes. Finally, we provide qualitative and quantitative evidence that this incorporation of functional inter-relationships enables the discovery of interesting biology in the form of novel functional annotations for several yeast proteins, such as Sna4, Rtn1 and Lin1.</p> <p>Conclusion</p> <p>We implemented and evaluated a methodology for incorporating interrelationships between functional classes into a standard classification-based protein function prediction algorithm. Our results show that this incorporation can help improve the accuracy of such algorithms, and help uncover novel biology in the form of previously unknown functional annotations. The complete source code, a sample data set and the additional files for this paper are available free of charge for non-commercial use at <url>http://www.cs.umn.edu/vk/gaurav/functionalsimilarity/</url>.</p

Directing Experimental Biology: A Case Study in Mitochondrial Biogenesis

Computational approaches have promised to organize collections of functional genomics data into testable predictions of gene and protein involvement in biological processes and pathways. However, few such predictions have been experimentally validated on a large scale, leaving many bioinformatic methods unproven and underutilized in the biology community. Further, it remains unclear what biological concerns should be taken into account when using computational methods to drive real-world experimental efforts. To investigate these concerns and to establish the utility of computational predictions of gene function, we experimentally tested hundreds of predictions generated from an ensemble of three complementary methods for the process of mitochondrial organization and biogenesis in Saccharomyces cerevisiae. The biological data with respect to the mitochondria are presented in a companion manuscript published in PLoS Genetics (doi:10.1371/journal.pgen.1000407). Here we analyze and explore the results of this study that are broadly applicable for computationalists applying gene function prediction techniques, including a new experimental comparison with 48 genes representing the genomic background. Our study leads to several conclusions that are important to consider when driving laboratory investigations using computational prediction approaches. While most genes in yeast are already known to participate in at least one biological process, we confirm that genes with known functions can still be strong candidates for annotation of additional gene functions. We find that different analysis techniques and different underlying data can both greatly affect the types of functional predictions produced by computational methods. This diversity allows an ensemble of techniques to substantially broaden the biological scope and breadth of predictions. We also find that performing prediction and validation steps iteratively allows us to more completely characterize a biological area of interest. While this study focused on a specific functional area in yeast, many of these observations may be useful in the contexts of other processes and organisms