Outcome prediction based on microarray analysis: a critical perspective on methods

<p>Abstract</p> <p>Background</p> <p>Information extraction from microarrays has not yet been widely used in diagnostic or prognostic decision-support systems, due to the diversity of results produced by the available techniques, their instability on different data sets and the inability to relate statistical significance with biological relevance. Thus, there is an urgent need to address the statistical framework of microarray analysis and identify its drawbacks and limitations, which will enable us to thoroughly compare methodologies under the same experimental set-up and associate results with confidence intervals meaningful to clinicians. In this study we consider gene-selection algorithms with the aim to reveal inefficiencies in performance evaluation and address aspects that can reduce uncertainty in algorithmic validation.</p> <p>Results</p> <p>A computational study is performed related to the performance of several gene selection methodologies on publicly available microarray data. Three basic types of experimental scenarios are evaluated, i.e. the independent test-set and the 10-fold cross-validation (CV) using maximum and average performance measures. Feature selection methods behave differently under different validation strategies. The performance results from CV do not mach well those from the independent test-set, except for the support vector machines (SVM) and the least squares SVM methods. However, these wrapper methods achieve variable (often low) performance, whereas the hybrid methods attain consistently higher accuracies. The use of an independent test-set within CV is important for the evaluation of the predictive power of algorithms. The optimal size of the selected gene-set also appears to be dependent on the evaluation scheme. The consistency of selected genes over variation of the training-set is another aspect important in reducing uncertainty in the evaluation of the derived gene signature. In all cases the presence of outlier samples can seriously affect algorithmic performance.</p> <p>Conclusion</p> <p>Multiple parameters can influence the selection of a gene-signature and its predictive power, thus possible biases in validation methods must always be accounted for. This paper illustrates that independent test-set evaluation reduces the bias of CV, and case-specific measures reveal stability characteristics of the gene-signature over changes of the training set. Moreover, frequency measures on gene selection address the algorithmic consistency in selecting the same gene signature under different training conditions. These issues contribute to the development of an objective evaluation framework and aid the derivation of statistically consistent gene signatures that could eventually be correlated with biological relevance. The benefits of the proposed framework are supported by the evaluation results and methodological comparisons performed for several gene-selection algorithms on three publicly available datasets.</p

TOWARDS THE ENZYMATIC CONVERSION OF CHITIN TO CHITOSAN: PURIFICATION, CLONING AND CHARACTERIZATION OF CHITIN DEACETYLASE FROM THE FUNGUS MUCOR ROUXII

Η ΜΕΤΑΤΡΟΠΗ ΤΗΣ ΧΙΤΙΝΗΣ ΣΤΗΝ ΑΠΑΚΕΤΥΛΙΩΜΕΝΗ ΜΟΡΦΗ, ΠΟΥ ΟΝΟΜΑΖΕΤΑΙ ΧΙΤΟΖΑΝΗ, ΠΑΡΕΧΕΙ ΣΤΟ ΠΟΛΥΜΕΡΕΣ ΝΕΕΣ ΙΔΙΟΤΗΤΕΣ ΧΡΗΣΙΜΕΣ ΓΙΑ ΠΟΛΛΕΣ ΕΦΑΡΜΟΓΕΣ. ΤΟ ΕΝΖΥΜΟ ΤΟ ΟΠΟΙΟ ΜΕΤΑΤΡΕΠΕΙ ΤΗ ΧΙΤΙΝΗ ΣΕ ΧΙΤΟΖΑΝΗ ΟΝΟΜΑΖΕΤΑΙ ΑΠΑΚΕΤΥΛΑΣΗ ΤΗΣ ΧΙΤΙΝΗΣ ΚΑΙ ΥΠΑΡΧΕΙ ΣΕ ΑΡΚΕΤΟΥΣ ΜΥΚΗΤΕΣ. Η ΑΠΑΚΕΤΥΛΑΣΗ ΤΗΣ ΧΙΤΙΝΗΣ ΤΟΥ ΜΥΚΗΤΑ MUCOR ROUXII ΑΠΟΜΟΝΩΘΗΚΕ ΚΑΙ ΧΑΡΑΚΤΗΡΙΣΤΗΚΕ ΛΕΠΤΟΜΕΡΙΑΚΑ. ΜΕΤΑ ΤΗΝ ΚΛΩΝΟΠΟΙΗΣΗ ΤΟΥ CDNA ΤΗΣ ΑΠΑΚΕΤΥΛΑΣΗΣ ΤΗΣ ΧΙΤΙΝΗΣ ΕΓΙΝΕ ΦΑΝΕΡΗ Η ΟΜΟΙΟΤΗΤΑ ΤΗΣ ΑΠΑΚΕΤΥΛΑΣΗΣ ΤΗΣ ΧΙΤΙΝΗΣ ΜΕ ΤΗ ΠΡΩΤΕΙΝΗ NODB ΤΩΝ ΡΙΖΟΒΙΩΝ ΚΑΙ ΜΕ ΜΕΡΙΚΕΣ ΠΡΩΤΕΙΝΕΣ ΑΠΟ ΑΚΤΙΝΟΜΥΚΗΤΕΣ ΚΑΙ ΒΑΚΙΛΛΟΥΣ ΟΙ ΟΠΟΙΕΣ ΔΕΝ ΕΧΟΥΝ ΑΚΟΜΑ ΧΑΡΑΚΤΗΡΙΣΤΕΙ. ΟΙ ΟΜΟΙΟΤΗΤΕΣ ΑΥΤΕΣ ΥΠΟΔΕΙΚΝΥΟΥΝ ΤΗ ΛΕΙΤΟΥΡΓΙΚΗ ΣΧΕΣΗ ΑΥΤΩΝ ΤΩΝ ΕΞΕΛΙΚΤΙΚΑ ΑΠΟΜΑΚΡΥΣΜΕΝΩΝ ΠΡΩΤΕΙΝΩΝ.CHITOSAN, THE DEACETYLATED FORM OF CHITIN, PRESENTS MANY VALUABLE PROPERTIES FAVORABLE FOR A WIDE VARIETY OF APPLICATIONS. CHITIN DEACETYLASE, THE ENZYME WHICH CONVERTS CHITIN TO CHITOSAN, EXISTS IN SEVERAL FUNGI. THE ENZYME HAS BEENPURIFIED FROM THE ZYGOMYCETES MUCOR ROUXII AND HAS BEEN FURTHER CHARACTERIZED. CDNA CLONING OF CHITIN DEACETYLASE REVEALED SIGNIFICANT SIMILARITIES OF THE ENZYME TO THE RHIZOBIAL NODB PROTEINS AND TO UNCHARACTERIZED PROTEINS ENCODED BY ACTINOMYCETES AND BACILLI. THESE SIMILARITIES SUGGEST THE FUNCTIONAL HOMOLOGY OF THESE EVOLUTIONARILY DISTANT PROTEINS

Towards Optimal Microarray Universal Reference Sample Designs: An In-Silico Optimization Approach

Part 19: Computational Intelligence Applications in Bioinformatics (CIAB) WorkshopInternational audienceAssessment of the reliability of microarray experiments as well as their cross-laboratory/platform reproducibility rise as the major need. A critical challenge concerns the design of optimal Universal Reference RNA (URR) samples in order to maximize detectable spots in two-color/channel microarray experiments, decrease the variability of microarray data, and finally ease the comparison between heterogeneous microarray datasets. Towards this target we devised and present an in-silico (binary) optimization process the solutions of which present optimal URR sample designs. Setting a cut-off threshold value over which a gene is considered as detectably expressed enables the process. Experimental results are quite encouraging and the related discussion highlights the suitability and flexibility of the approach

Comparative Transcriptome Analysis of Two Olive Cultivars in Response to NaCl-Stress

Background: Olive (Olea europaea L.) cultivation is rapidly expanding and low quality saline water is often used for irrigation. The molecular basis of salt tolerance in olive, though, has not yet been investigated at a system level. In this study a comparative transcriptomics approach was used as a tool to unravel gene regulatory networks underlying salinity response in olive trees by simulating as much as possible olive growing conditions in the field. Specifically, we investigated the genotype-dependent differences in the transcriptome response of two olive cultivars, a salt-tolerant and a salt-sensitive one. Methodology/Principal Findings: A 135-day long salinity experiment was conducted using one-year old trees exposed to NaCl stress for 90 days followed by 45 days of post-stress period during the summer. A cDNA library made of olive seedling mRNAs was sequenced and an olive microarray was constructed. Total RNA was extracted from root samples after 15, 45 and 90 days of NaCl-treatment as well as after 15 and 45 days of post-treatment period and used for microarray hybridizations. SAM analysis between the NaCl-stress and the post-stress time course resulted in the identification of 209 and 36 differentially expressed transcripts in the salt–tolerant and salt–sensitive cultivar, respectively. Hierarchical clustering revealed two major, distinct clusters for each cultivar. Despite the limited number of probe sets, transcriptional regulatory networks were constructed for both cultivars while several hierarchically-clustered interacting transcription factor regulators such as JERF and bZIP homologues were identified. Conclusions/Significance: A systems biology approach was used and differentially expressed transcripts as well as regulatory interactions were identified. The comparison of the interactions among transcription factors in olive with those reported for Arabidopsis might indicate similarities in the response of a tree species with Arabidopsis at the transcriptional level under salinity stress

Revealing disease mechanisms via coupling molecular pathways scaffolds and microarrays: A study on the wilm’s tumor disease

Summarization: Moving towards the realization of genomic data in clinical practice, and following an individualized healthcare approach, the function and regulation of genes has to be deciphered and manifested. This is even more possible after the later advances in the area of molecular biology and biotechnology that have brought vast amount of invaluable data to the disposal of researchers. Two of the most significant forms of data come form microarray gene expression sources, and gene interactions sources - as encoded in Gene Regulatory Pathways (GRPs). The usual computational task involving microarray experiments is the gene selection procedure while, GRPs are used mainly for data annotation. In this study we present a novel perception of these resources. Initially we locate all functional paths encoded in GRPs and we try to assess which of them are compatible with the gene-expression values of samples that belong to different clinical categories (diseases and phenotypes). Then we apply usual feature selection techniques to identify the paths that discriminate between the different clinical phenotypes providing a paradigm shift over the usual gene selection approaches. The differential ability of the selected paths is evaluated and their biological relevance is assessed. The whole approach was applied on the Wilm's tumor domain with very good and indicative results.Παρουσιάστηκε στο: Biomedical Informatics and Intelligent Methods in the support of Genomic Medicin

Revitalization of the Greek Vitis database ::a multimedia web-backed genetic database for germplasm management of Vitis resources in Greece

Lefort and Roubelakis-Angelakis ([2000. The Greek Vitis Database: A multimedia web-backed genetic database for germplasm management of Vitis resources in Greece. Journal of Wine Research, 11(3), 233–242. https://doi.org/10.1080/713684241)] were the first to develop a Greek Vitis multimedia web-backed service at the Laboratory of Plant Physiology and Biotechnology of the University of Crete 20 years ago. This service was named Greek Vitis Database (GVD) and it provided free access to six databases, gathering information about Greek cultivars of Vitis vinifera: an information database; a nuclear single sequence repeats (nSSR) microsatellite profiles database; a chloroplast microsatellite (cpSSR) database; a combined nSSR – cpSSR profiles database; an ampelographic database; and a rootstock database. Information and descriptive images were combined with SSR profiles. Although simple sequence repeats are still the markers of choice for compilation, standardization and exchange of information regarding grapevine genetic resources, the advances in computing technology through the years made the GDV inactive. This report is to announce the renovation and revitalization of GVD using new computing technologies. The GVD can now be accessible at http://greekvitisdb.biology.uoc.gr or in the previous address http://www.biology.uoc.gr/gvd redirected

Molecular identification and geographic origin of a post-Medieval elephant finding from southwestern Portugal using high-throughput sequencing

Molecular species identification plays a crucial role in archaeology and palaeontology, especially when diagnostic morphological characters are unavailable. Molecular markers have been used in forensic science to trace the geographic origin of wildlife products, such as ivory. So far, only a few studies have applied genetic methods to both identify the species and circumscribe the provenance of historic wildlife trade material. Here, by combining ancient DNA methods and genome skimming on a historical elephantid tooth found in southwestern Portugal, we aimed to identify its species, infer its placement in the elephantid phylogenetic tree, and triangulate its geographic origin. According to our results the specimen dates back to the eighteenth century CE and belongs to a female African forest elephant (non-hybrid Loxodonta cyclotis individual) geographically originated from west-west-central Africa, from areas where one of the four major mitochondrial clades of L. cyclotis is distributed. Historical evidence supports our inference, pointing out that the tooth should be considered as post-Medieval raw ivory trade material between West Africa and Portugal. Our study provides a comprehensive approach to study historical products and artefacts using archaeogenetics and contributes towards enlightening cultural and biological historical aspects of ivory trade in western Europe