Evaluation of statistical correlation and validation methods for construction of gene co-expression networks

High-throughput technologies such as microarrays have led to the rapid accumulation of large scale genomic data providing opportunities to systematically infer gene function and co-expression networks. Typical steps of co-expression network analysis using microarray data consist of estimation of pair-wise gene co-expression using some similarity measure, construction of co-expression networks, identification of clusters of co-expressed genes and post-cluster analyses such as cluster validation. This dissertation is primarily concerned with development and evaluation of approaches for the first and the last steps – estimation of gene co-expression matrices and validation of network clusters. Since clustering methods are not a focus, only a paraclique clustering algorithm will be used in this evaluation. First, a novel Bayesian approach is presented for combining the Pearson correlation with prior biological information from Gene Ontology, yielding a biologically relevant estimate of gene co-expression. The addition of biological information by the Bayesian approach reduced noise in the paraclique gene clusters as indicated by high silhouette and increased homogeneity of clusters in terms of molecular function. Standard similarity measures including correlation coefficients from Pearson, Spearman, Kendall’s Tau, Shrinkage, Partial, and Mutual information, and Euclidean and Manhattan distance measures were evaluated. Based on quality metrics such as cluster homogeneity and stability with respect to ontological categories, clusters resulting from partial correlation and mutual information were more biologically relevant than those from any other correlation measures. Second, statistical quality of clusters was evaluated using approaches based on permutation tests and Mantel correlation to identify significant and informative clusters that capture most of the covariance in the dataset. Third, the utility of statistical contrasts was studied for classification of temporal patterns of gene expression. Specifically, polynomial and Helmert contrast analyses were shown to provide a means of labeling the co-expressed gene sets because they showed similar temporal profiles

AUGUR: Forecasting the Emergence of New Research Topics

Being able to rapidly recognise new research trends is strategic for many stakeholders, including universities, institutional funding bodies, academic publishers and companies. The literature presents several approaches to identifying the emergence of new research topics, which rely on the assumption that the topic is already exhibiting a certain degree of popularity and consistently referred to by a community of researchers. However, detecting the emergence of a new research area at an embryonic stage, i.e., before the topic has been consistently labelled by a community of researchers and associated with a number of publications, is still an open challenge. We address this issue by introducing Augur, a novel approach to the early detection of research topics. Augur analyses the diachronic relationships between research areas and is able to detect clusters of topics that exhibit dynamics correlated with the emergence of new research topics. Here we also present the Advanced Clique Percolation Method (ACPM), a new community detection algorithm developed specifically for supporting this task. Augur was evaluated on a gold standard of 1,408 debutant topics in the 2000-2011 interval and outperformed four alternative approaches in terms of both precision and recall

The Effect of Timbre and Vibrato on Vocal Pitch Matching Accuracy

Research has shown that singers are better able to match pitch when the target stimulus has a timbre close to their own voice. This study seeks to answer the following questions: 1. Do classically trained female singers more accurately match pitch when the target stimulus is more similar to their own timbre? 2. Does the ability to match pitch vary with increasing pitch? 3. Does the ability to match pitch differ depending on whether the target stimulus is produced with or without vibrato? 4. Are mezzo sopranos less accurate than sopranos? Stimuli: Source signals were synthesized with a source slope of -12dB/octave using vibrato and without vibrato at each of the frequencies, C4, B4 and F5. These source signals were filtered using 5 formant patterns (A-E) of vowel /a/ constituting a total of 30 stimuli (5 formant patterns*3pitches*2 vibrato conditions). Procedure: Ten sopranos and 10 mezzo-sopranos with at least 3 years of individual voice training were recruited from the University Of Tennessee School Of Music and the Knoxville Opera Company. Each singer attempted to vocally match the pitch of all 30 stimuli presented twice in a random order. Analysis and results: Pitch matching accuracy was measured in terms of the difference in cents between the target and the experimental productions at two locations, (1) pre-phonatory set (2) mid-point of the vowel. Accuracy of pitch matching was compared across vibrato and nonvibrato conditions. Results indicated that there was no significant effect of formant pattern on pitch matching accuracy. With increasing pitch from C4 to F5, pitch matching accuracy increased in mid-point of the vowel condition but not in pre-phonatory set condition. Mezzosopranos moved towards being in tune from pre-phonatory to mid-point of the vowel. However, sopranos at C4, sang closer to being in tune at pre-phonatory, but lowered the pitch at the midpoint of the vowel. Presence or absence of vibrato did not affect the pitch matching accuracy. However, the interesting finding of the study was that singers attempted to match the timbre of stimuli with vibrato. Results are discussed in terms of interactions between pitch and timbre from auditory perceptual as well as physiological point of view and how current theories of pitch perception relate to this phenomenon. Neither physiological nor auditory perceptual mechanisms provide complete explanations for the results obtained in the study. From a perceptual point of view, an interaction between pitch and timbre seems to be more complex, for spectral and temporal theories are limited in explaining these interactions. Also, possible explanations for the phenomenon of timbre matching are provided

Dynamic property characterization of ionic polymer metal composite (Ipmc)

In this thesis dynamic properties of Ionic Polymer Metal Composite (IPMC) is studied. The ionic polymer (IPMC) is made out of a high polymer gel film whose surface is plated with platinum. This ionic polymer finds its application in future as artificial muscle. Analytical modeling method for both single and segmented ionic polymer which can exhibit varying curvature along the polymer was introduced. This segmented ionic polymer can generate more flexible propulsion compared with a single strip ionic polymer where only forward propulsion can be generated by a simple oscillatory bending motion. It is well known in biomimetic system research that a simple bending motion has lower efficiency than a snake-like wavy motion in propulsion. In this segmented ionic polymer each segment can be bent individually. This segmented ionic polymer design consists of a number of independent electrode sections along the length of the ionic polymer to realize the undulatory motion by selectively activating each segment. The magnitude of curvature can be controlled by adjusting the voltage level applied across each segment. In this thesis we focus on the development of an analytical model to predict the deflection of this single and segmented ionic polymers and the model is validated with experimental results. Due to the complexity of the polymer, it is necessary to find the dynamic parameters from the experimental data. After proper tuning of dynamic model, this can be used for various control applications including the underwater robotic propulsor device design and others. The dynamic model developed in this work reasonable complies with experimental data and can be further developed for future control algorithm design

Spectral methods for modeling microstructure evolution in deformation processing of cubic polycrystalline metals

The mechanical properties of engineering materials are directly controlled by the underlying microstructure, which in turn is governed by the processing methods. The complete description of microstructure is extremely complex and is also not required for many microstructure-properties relationships of interest. The relevant details of the microstructure that influence strongly the elastic-plastic properties of the material include the lattice orientation distribution (texture), the grain size and shape distribution, and the arrangement and distribution of dislocation networks on the various slip systems in the constituent crystals. Of these, the crystallographic texture is perhaps the most important aspect of microstructure that has a strong influence on the elastic and the initial yield properties of most polycrystalline materials used in the manufacture of engineering components. It should also be noted that crystallographic texture is likely to have the dominant effect on the inherent anisotropy exhibited by these materials.The objective of this thesis is to provide a mathematical framework for the development of material databases; capturing the relevant details of the microstructure, while paying attention to inherent anisotropy of properties associated with them. Here crystallographic texture is the only microstructural parameter that is considered. This work is motivated by a new design paradigm called microstructure sensitive design (MSD) which employs statistical description of microstructure and its core feature is the efficient spectral representations of microstructure-property-processing linkages. Using the MSD framework as the basis, novel computational methodologies were developed in this work to build material spectral databases in single phase cubic polycrystalline materials. These databases were critically evaluated in three different cases: 1) To predict the effective macroscale elastic properties in perfectly disordered copper polycrystals 2) Evolution of the microstructure and the concomitant anisotropic stress-strain response during deformation processes in FCC polycrystals and (3) in developing a processing recipe to obtain a targeted texture using selected processing techniques.Ph.D., Materials Science and Engineering -- Drexel University, 200

Serum transferrin receptor-ferritin index as a marker of iron deficiency anemia in active inflammatory bowel disease patients in Indian population

Background: Anemia is most common complication in IBD (inflammatory bowel disease). The aim of the study was to assess the sTfR-F (soluble transferrin receptor-ferritin) index as early marker of IDA (iron deficiency anaemia) in IBD.Methods: Retrospective cross sectional study has 480 cases of IBD (group I ) with controls 220 (group II), CBP, serum hsCRP, serum iron, TIBC (total iron binding capacity), sTfR, ferritin, fecal calprotectin, vitamin B12, folic acid were assessed.Results: In study I, group I was compared with group II showed (66.5%) patients had active disease and in that 65.0% of UC, 32.1% of CD and 2.9% others colitis had anemia. In study II, subgroup I 56.4% had IDA subgroup II 7.3% had ferritin between 30-100 ng/ml combi subgroup III 23.3% had ferritin>100 ng/ml (ACD, anaemia of chronic disease) subgroup IV 5.6% had vitamin B12 and folic acid deficiency excluding sTfR-F analysis. In study III, subdivided to identify IDA with sTfR-F index as group A 60.8% had sTfR-F index>2, group B 32.6% had sTfR-F index=1-2 and group C 3 (6.2%) had sTfR-F index<1. Intially diagnosed IDA was 56.4%, in addition with group A, IDA has increased by 66.5%. In study IV, in IDA, sensitivity of sTfR-F index was100%, sTfR 89% and SF 85%. Specificity of sTfR and sTfR-F index were 80.60% and SF has low specificity 73.90%. In study V, a statistical significance was seen more in female than male and in children than in adults with sTfR-F index in IDA.Conclusions: sTfR-F index as an early diagnostic marker, in differentiating IDA, ACD and combi in IBD patients