250 research outputs found
Knowledge-based identification of multicomponent therapies
No full textIn recent years, several approaches have been proposed to improve the capacity of pharmaceutical research to support personalized care. An approach that takes advantages of the large amount of biological knowledge continuously collected in different repositories could improve the drug discovery process. In this context, networks are increasingly used as universal platforms to integrate the knowledge available on a complex disease. The objective of this work is to provide a knowledge-based strategy to support polypharmacology, a new promising approach for drug discovery. Given a specific disease, the proposed method is able to identify the possible targets by analysing the topological features of the related network. The network-based analysis defines a score aimed at ranking the targets and selecting their best combinations. The results obtained on Type 2 Diabetes Mellitus highlight the ability of the method to retrieve novel target candidates related to the considered diseas
Network-based target ranking for polypharmacological therapies
No full textAbstractWith the growing understanding of complex diseases, the focus of drug discovery has shifted from the well-accepted “one target, one drug” model, to a new “multi-target, multi-drug” model, aimed at systemically modulating multiple targets. In this context, polypharmacology has emerged as a new paradigm to overcome the recent decline in productivity of pharmaceutical research. However, finding methods to evaluate multicomponent therapeutics and ranking synergistic agent combinations is still a demanding task.At the same time, the data gathered on complex diseases has been progressively collected in public data and knowledge repositories, such as protein–protein interaction (PPI) databases. The PPI networks are increasingly used as universal platforms for data integration and analysis. A novel computational network-based approach for feasible and efficient identification of multicomponent synergistic agents is proposed in this paper. Given a complex disease, the method exploits the topological features of the related PPI network to identify possible combinations of hit targets. The best ranked combinations are subsequently computed on the basis of a synergistic score. We illustrate the potential of the method through a study on Type 2 Diabetes Mellitus. The results highlight its ability to retrieve novel target candidates, which role is also confirmed by the analysis of the related literature
Knowledge-based bioinformatics for the study of mammalian oocytes
No full textBioinformatics tools have been recently applied to study the differentiation of the mammalian oocyte during folliculogenesis. In this review, we will summarize our knowledge of 1) the use of biological databases for the extraction of relevant information, 2) bioinformatics methods for knowledge extraction and representation, 3) the application of these methods to the study of mammalian oocyte differentiation and 4) state-of the-art prediction approaches for the assessment and estimation of the cell differentiation status
Ranking and 1-dimensional projection of cell development transcription profiles
No full textGenome-scale transcription profile is known to be a good reporter of the state of the cell. Much of the early predictive modelling and cell-type clustering relied on this relation and has experimentally confirmed it. We have examined if this also holds for prediction of cell's staging, and focused on the inference of stage prediction models for stem cell development. We show that the problem relates to rank learning and, from the user's point of view, to projection of transcription profile data to a single dimension. Our comparison of several state-of-the-art algorithms on 10 data sets from Gene Expression Omnibus shows that rank-learning can be successfully applied to developmental cell staging, and that relatively simple techniques can perform surprisingly well
Gianni Colombo nelle fotografie di Ugo Mulas: corpo e comportamento
No full textAmong the photographic sequences dedicated by Ugo Mulas to the artists of his time, those focusing on Gianni Colombo’s works occupy a critically fundamental position: not only for their frequency and quantity, but also and above all for the recurring and never passive presence of figures, starting with Colombo himself, who appears in these images with an unusual insistence: above all, not casually or purely for a portrait, but according to deeply significant performative coordinates. The article analyzes these images in detail, which I have been studying and so far only partially published, particularly in the monograph Gianni Colombo. The Body and the Space 1959-1980 (2015). In these photographs, Colombo's works and environments emerge, thanks to Mulas’s photographic vision, in their very nature of real “behavioural activators”, deconstructing the vision beyond the individuality of the experience, thanks to the presence of one or more bodies that act, also in relation and reciprocal participation with one another. The analysis is articulated around the centrality of the notion of “behaviour”, both for Mulas’s photographic vision and for Colombo’s artistic one: not only in fact the reflection on “behaviour” recurs in many writings by both, but is also explicit in their creative practice as a key through which to reinvent the image.Tra le sequenze fotografiche dedicate da Ugo Mulas agli artisti a lui contemporanei, quelle che si concentrano sulle opere di Gianni Colombo occupano una posizione criticamente fondamentale: non solo per la loro frequenza e ampiezza quantitativa, ma anche e soprattutto per la presenza ricorrente e mai passiva di figure, a partire da Colombo stesso che si ritrova in queste immagini con una insistenza inconsueta, e soprattutto non casuale o puramente ritrattistica, ma secondo coordinate performative profondamente significanti. L’articolo analizza queste immagini, da me studiate e sinora solo parzialmente pubblicate in particolare nella monografia Gianni Colombo. The Body and the Space 1959-1980 (2015). Fotografie in cui opere e ambienti di Colombo emergono, grazie alla lettura fotografica di Mulas, nella loro più propria natura di veri e propri “attivatori comportamentali”, destrutturando la visione oltre l’individualità dell’esperienza, grazie alla presenza di uno o più corpi che agiscono, anche in relazione e partecipazione reciproca tra loro. La trattazione si articola attorno alla centralità della nozione di “comportamento”, sia per la visione fotografica di Mulas che per quella artistica di Colombo: non solo infatti la riflessione sul “comportamento” ricorre in molti scritti di entrambi, ma si esplicita anche nella loro pratica creativa come chiave attraverso cui reinventare l’immagine
On quality of different annotation sources for gene expression analysis
No full textMining of biomedical data increasingly relies on utility of knowledge repositories. In gene expression analysis, these are often used for gene labeling with all assumption that similarly annotated genes have similar expression profiles. In the paper we use this assumption to craft, a method with which we scored six different, annotation sources, (e.g., Gene Ontology, PubMed, and MeSH annotations) for their utility in gene expression data analysis. Experiments show that the sources that include manual curation perform well and, for instance, score better than automatic annotation from gene-related PubMed abstracts. We also show that there is no clear winner, pointing at, the need for methods that; Could successfully integrate annotations from different sources
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