Enhancing random forests performance in microarray data classification

Random forests are receiving increasing attention for classification of microarray datasets. We evaluate the effects of a feature selection process on the performance of a random forest classifier as well as on the choice of two critical parameters, i.e. the forest size and the number of features chosen at each split in growing trees. Results of our experiments suggest that parameters lower than popular default values can lead to effective and more parsimonious classification models. Growing few trees on small subsets of selected features, while randomly choosing a single variable at each split, results in classification performance that compares well with state-of-art studies

BioCloud Search EnGene: Surfing Biological Data on the Cloud

The massive production and spread of biomedical data around the web introduces new challenges related to identify computational approaches for providing quality search and browsing of web resources. This papers presents BioCloud Search EnGene (BSE), a cloud application that facilitates searching and integration of the many layers of biological information offered by public large-scale genomic repositories. Grounding on the concept of dataspace, BSE is built on top of a cloud platform that severely curtails issues associated with scalability and performance. Like popular online gene portals, BSE adopts a gene-centric approach: researchers can find their information of interest by means of a simple “Google-like” query interface that accepts standard gene identification as keywords. We present BSE architecture and functionality and discuss how our strategies contribute to successfully tackle big data problems in querying gene-based web resources. BSE is publically available at: http://biocloud-unica.appspot.com/

Cloud-based solutions supporting data and knowledge integration in bioinformatics

In recent years, computer advances have changed the way the science progresses and have boosted studies in silico; as a result, the concept of “scientific research” in bioinformatics has quickly changed shifting from the idea of a local laboratory activity towards Web applications and databases provided over the network as services. Thus, biologists have become among the largest beneficiaries of the information technologies, reaching and surpassing the traditional ICT users who operate in the field of so-called "hard science" (i.e., physics, chemistry, and mathematics). Nevertheless, this evolution has to deal with several aspects (including data deluge, data integration, and scientific collaboration, just to cite a few) and presents new challenges related to the proposal of innovative approaches in the wide scenario of emergent ICT solutions. This thesis aims at facing these challenges in the context of three case studies, being each case study devoted to cope with a specific open issue by proposing proper solutions in line with recent advances in computer science. The first case study focuses on the task of unearthing and integrating information from different web resources, each having its own organization, terminology and data formats in order to provide users with flexible environment for accessing the above resources and smartly exploring their content. The study explores the potential of cloud paradigm as an enabling technology to severely curtail issues associated with scalability and performance of applications devoted to support the above task. Specifically, it presents Biocloud Search EnGene (BSE), a cloud-based application which allows for searching and integrating biological information made available by public large-scale genomic repositories. BSE is publicly available at: http://biocloud-unica.appspot.com/. The second case study addresses scientific collaboration on the Web with special focus on building a semantic network, where team members, adequately supported by easy access to biomedical ontologies, define and enrich network nodes with annotations derived from available ontologies. The study presents a cloud-based application called Collaborative Workspaces in Biomedicine (COWB) which deals with supporting users in the construction of the semantic network by organizing, retrieving and creating connections between contents of different types. Public and private workspaces provide an accessible representation of the collective knowledge that is incrementally expanded. COWB is publicly available at: http://cowb-unica.appspot.com/. Finally, the third case study concerns the knowledge extraction from very large datasets. The study investigates the performance of random forests in classifying microarray data. In particular, the study faces the problem of reducing the contribution of trees whose nodes are populated by non-informative features. Experiments are presented and results are then analyzed in order to draw guidelines about how reducing the above contribution. With respect to the previously mentioned challenges, this thesis sets out to give two contributions summarized as follows. First, the potential of cloud technologies has been evaluated for developing applications that support the access to bioinformatics resources and the collaboration by improving awareness of user's contributions and fostering users interaction. Second, the positive impact of the decision support offered by random forests has been demonstrated in order to tackle effectively the curse of dimensionality

Blood flow controls bone vascular function and osteogenesis

While blood vessels play important roles in bone homeostasis and repair, fundamental aspects of vascular function in the skeletal system remain poorly understood. Here we show that the long bone vasculature generates a peculiar flow pattern, which is important for proper angiogenesis. Intravital imaging reveals that vessel growth in murine long bone involves the extension and anastomotic fusion of endothelial buds. Impaired blood flow leads to defective angiogenesis and osteogenesis, and downregulation of Notch signalling in endothelial cells. In aged mice, skeletal blood flow and endothelial Notch activity are also reduced leading to decreased angiogenesis and osteogenesis, which is reverted by genetic reactivation of Notch. Blood flow and angiogenesis in aged mice are also enhanced on administration of bisphosphonate, a class of drugs frequently used for the treatment of osteoporosis. We propose that blood flow and endothelial Notch signalling are key factors controlling ageing processes in the skeletal system

Blood Flow Restriction Training Reduces Blood Pressure During Exercise Without Affecting Metaboreflex Activity

Objective: Blood flow restriction training (BFRT) has been proposed to induce muscle hypertrophy, but its safety remains controversial as it may increase mean arterial pressure (MAP) due to muscle metaboreflex activation. However, BFR training also causes metabolite accumulation that may desensitize type III and IV nerve endings, which trigger muscle metaboreflex. Then, we hypothesized that a period of BFR training would result in blunted hemodynamic activation during muscle metaboreflex.Methods: 17 young healthy males aged 18–25 yrs enrolled in this study. Hemodynamic responses during muscle metaboreflex were assessed by means of postexercise muscle ischemia (PEMI) at baseline (T0) and after 1 month (T1) of dynamic BFRT. BFRT consisted of 3-min rhythmic handgrip exercise applied 3 days/week (30 contractions per minute at 30% of maximum voluntary contraction) in the dominant arm. On the first week, the occlusion was set at 75% of resting systolic blood pressure (always obtained after 3 min of resting) and increased 25% every week, until reaching 150% of resting systolic pressure at week four. Hemodynamic measurements were assessed by means of impedance cardiography.Results: BFRT reduced MAP during handgrip exercise (T1: 96.3 ± 8.3 mmHg vs. T0: 102.0 ± 9.53 mmHg, p = 0.012). However, no significant time effect was detected for MAP during the metaboreflex activation (P > 0.05). Additionally, none of the observed hemodynamic outcomes, including systemic vascular resistance (SVR), showed significant difference between T0 and T1 during the metaboreflex activation (P > 0.05).Conclusion: BFRT reduced blood pressure during handgrip exercise, thereby suggesting a potential hypotensive effect of this modality of training. However, MAP reduction during handgrip seemed not to be provoked by lowered metaboreflex activity

Genome-wide Analyses Identify KIF5A as a Novel ALS Gene

To identify novel genes associated with ALS, we undertook two lines of investigation. We carried out a genome-wide association study comparing 20,806 ALS cases and 59,804 controls. Independently, we performed a rare variant burden analysis comparing 1,138 index familial ALS cases and 19,494 controls. Through both approaches, we identified kinesin family member 5A (KIF5A) as a novel gene associated with ALS. Interestingly, mutations predominantly in the N-terminal motor domain of KIF5A are causative for two neurodegenerative diseases: hereditary spastic paraplegia (SPG10) and Charcot-Marie-Tooth type 2 (CMT2). In contrast, ALS-associated mutations are primarily located at the C-terminal cargo-binding tail domain and patients harboring loss-of-function mutations displayed an extended survival relative to typical ALS cases. Taken together, these results broaden the phenotype spectrum resulting from mutations in KIF5A and strengthen the role of cytoskeletal defects in the pathogenesis of ALS.Peer reviewe

Oltre il Segno/OltreMare

La realizzazione di un volume contenente le incisioni scelte all’interno della Scuola di Grafica d’Arte dell’Accademia di Belle Arti di Palermo, coordinata dai Proff. Giovanni D’Alessandro e Riccardo Mazzarino rappresenta motivo di orgoglio e di soddisfazione per la nostra Istituzione che costruisce i percorsi didattici dei propri corsi a partire dall’esperienza laboratoriale. L’incisione grafica è tra le tecniche artistiche più antiche ma nel contempo più contemporanee. La gestualità intrinseca al segno, che si manifesta nella carta, svela universi della visione inaspettati.(Mario Zito - Direttore dell’Accademia di Belle Arti di Palermo) Il segno è il risultato di un gesto a volte deciso, a volte contorto, a volte leggero, i cui risultati spesso sono inattesi e sorprendenti. Il volume contiene esemplari di incisioni fortemente caratterizzanti della scuola di Grafica d’Arte che vanta all’interno del proprio corso di studi docenti-artisti che consapevoli della ricchezza del loro bagaglio esperienziale offrono agli studenti gli strumenti necessari per far sì che l’arte del saper fare artigianale, si trasformi in mera poetica artistica

Pre-filtering Features in Random Forests for Microarray Data Classification

Random forests have been applied, with promising results, in analyzing datasets with large dimensionality and are receiving increasing attention for classification of microarray datasets. This paper examines random forests from an experimental perspective. It first aims at confirming their effectiveness in microarray data classification, but its main contribution is two-fold: to evaluate the effects of a filtering process which precedes the actual construction of the random forest and, in addition, to provide some insights about the behavior of random forest critical parameters, i.e. the forest size and the number of variable chosen at each split in growing trees. We experimented tuning these critical parameters in a public microarray dataset within a filter method. The paper gives suggestions on the optimal choice of these parameters and presents results which compare well with state-of-art methods for micro-array classification

COWB: A cloud-based framework supporting collaborative knowledge management within biomedical communities

Despite the large acceptance of Semantic Web technologies and their key role in bioinformatics, some concerns begin to emerge about their suitability for supporting the requirements of collaborative environments where a research community shares and creates new knowledge. The paper discusses these concerns and proposes COWB (COllaborative Workspaces in Biomedicine), a framework which supports collaborative knowledge management in the context of biomedical communities. COWB is grounded on a multi-layer ontology-centric model. It harnesses both the semantic knowledge captured from ontologies and the functional knowledge about resources which extend the domain knowledge and support its management. Public and private workspaces provide an accessible representation of the collective knowledge that is incrementally created and allow the knowledge to cross the boundaries of closed local information. The paper presents the deployment of COWB in a cloud platform which severely curtails issues associated with scalability and performance. The paper shows the suitability of the proposed approach and aims to suggest how exploiting the potential of the Semantic Web technologies in the context of emergent technologies including Web 2.0, NoSQL databases and the cloud paradigm