Papers by Andrea Franceschini
SVD-Phy: Improved prediction of protein functional associations through singular value decomposition of phylogenetic profiles
Bioinformatics (Oxford, England), Jan 26, 2015
A successful approach for predicting functional associations between non-homologous genes is to c... more A successful approach for predicting functional associations between non-homologous genes is to compare their phylogenetic distributions. We have devised a phylogenetic profiling algorithm, SVD-Phy, which uses truncated singular value decomposition to address the problem of uninformative profiles giving rise to false positive predictions. Benchmarking the algorithm against the KEGG pathway database, we found that it has substantially improved performance over existing phylogenetic profiling methods. The software is available under the open-source BSD license at https://bitbucket.org/andrea/svd-phy CONTACT: lars.juhl.jensen@cpr.ku.dk.
AMIA ... Annual Symposium proceedings / AMIA Symposium. AMIA Symposium
Protein families and domains represent a very relevant resource useful to understand protein func... more Protein families and domains represent a very relevant resource useful to understand protein functions and interactions among their codifying genes. To perform evaluations of gene annotations sparsely available in numerous different databanks accessible via Internet, we previously developed GFINDer, a Web server that performs statistical analysis of functional and phenotypic annotations of gene lists. To exploit protein information present in Pfam and InterPro databanks, in GFINDer we integrated two new modules, that allow to annotate and statistically analyze user-classified nucleotide sequence with controlled information on related protein families, domains and functional sites.
International Journal of Material Forming, 2010
The study of the instability phenomena of polymer melts in capillary flows is of great technical ... more The study of the instability phenomena of polymer melts in capillary flows is of great technical relevance since, during an industrial die forming operation, these instabilities can give origin to a transition from a defect-free to a highly-defective extrudate. In this work, the instability phenomena exhibited in capillary flow by a blow moulding grade of high-density polyethylene (HDPE) were analyzed. In particular, by means of a capillary rheometer, which mimics polymer extrusion, the effects of specific extrusion parameters (temperature and imposed flow rate) on the oscillating flow, that takes place when "stick-slip" instabilities occur, were investigated.
AMIA ... Annual Symposium proceedings / AMIA Symposium. AMIA Symposium, 2006
Protein families and domains represent a very relevant resource useful to understand protein func... more Protein families and domains represent a very relevant resource useful to understand protein functions and interactions among their codifying genes. To perform evaluations of gene annotations sparsely available in numerous different databanks accessible via Internet, we previously developed GFINDer, a Web server that performs statistical analysis of functional and phenotypic annotations of gene lists. To exploit protein information present in Pfam and InterPro databanks, in GFINDer we integrated two new modules, that allow to annotate and statistically analyze user-classified nucleotide sequence with controlled information on related protein families, domains and functional sites.
Nucleic acids research, Jan 28, 2015
The many functional partnerships and interactions that occur between proteins are at the core of ... more The many functional partnerships and interactions that occur between proteins are at the core of cellular processing and their systematic characterization helps to provide context in molecular systems biology. However, known and predicted interactions are scattered over multiple resources, and the available data exhibit notable differences in terms of quality and completeness. The STRING database (http://string-db.org) aims to provide a critical assessment and integration of protein-protein interactions, including direct (physical) as well as indirect (functional) associations. The new version 10.0 of STRING covers more than 2000 organisms, which has necessitated novel, scalable algorithms for transferring interaction information between organisms. For this purpose, we have introduced hierarchical and self-consistent orthology annotations for all interacting proteins, grouping the proteins into families at various levels of phylogenetic resolution. Further improvements in version 10...
Journal of virology, 2014
The Bunyaviridae constitute a large family of enveloped animal viruses, many of which are importa... more The Bunyaviridae constitute a large family of enveloped animal viruses, many of which are important emerging pathogens. How bunyaviruses enter and infect mammalian cells remains largely uncharacterized. We used two genome-wide silencing screens with distinct small interfering RNA (siRNA) libraries to investigate host proteins required during infection of human cells by the bunyavirus Uukuniemi virus (UUKV), a late-penetrating virus. Sequence analysis of the libraries revealed that many siRNAs in the screens inhibited infection by silencing not only the intended targets but additional genes in a microRNA (miRNA)-like manner. That the 7-nucleotide seed regions in the siRNAs can cause a perturbation in infection was confirmed by using synthetic miRNAs (miRs). One of the miRs tested, miR-142-3p, was shown to interfere with the intracellular trafficking of incoming viruses by regulating the v-SNARE VAMP3, a strong hit shared by both siRNA screens. Inactivation of VAMP3 by the tetanus tox...
Proceedings of the National Academy of Sciences, 2014
Systematic genetic perturbation screening in human cells remains technically challenging. Typical... more Systematic genetic perturbation screening in human cells remains technically challenging. Typically, large libraries of chemically synthesized siRNA oligonucleotides are used, each designed to degrade a specific cellular mRNA via the RNA interference (RNAi) mechanism. Here, we report on data from three genome-wide siRNA screens, conducted to uncover host factors required for infection of human cells by two bacterial and one viral pathogen. We find that the majority of phenotypic effects of siRNAs are unrelated to the intended "on-target" mechanism, defined by full complementarity of the 21-nt siRNA sequence to a target mRNA. Instead, phenotypes are largely dictated by "off-target" effects resulting from partial complementarity of siRNAs to multiple mRNAs via the "seed" region (i.e., nucleotides 2-8), reminiscent of the way specificity is determined for endogenous microRNAs. Quantitative analysis enabled the prediction of seeds that strongly and specifically block infection, independent of the intended ontarget effect. This prediction was confirmed experimentally by designing oligos that do not have any on-target sequence match at all, yet can strongly reproduce the predicted phenotypes. Our results suggest that published RNAi screens have primarily, and unintentionally, screened the sequence space of microRNA seeds instead of the intended on-target space of protein-coding genes. This helps to explain why previously published RNAi screens have exhibited relatively little overlap. Our analysis suggests a possible way of identifying "seed reagents" for controlling phenotypes of interest and establishes a general strategy for extracting valuable untapped information from past and future RNAi screens.
Nucleic Acids Research, 2010
Over the last years, the publicly available knowledge on interactions between small molecules and... more Over the last years, the publicly available knowledge on interactions between small molecules and proteins has been steadily increasing. To create a network of interactions, STITCH aims to integrate the data dispersed over the literature and various databases of biological pathways, drug-target relationships and binding affinities. In STITCH 2, the number of relevant interactions is increased by incorporation of BindingDB, PharmGKB and the Comparative Toxicogenomics Database. The resulting network can be explored interactively or used as the basis for large-scale analyses. To facilitate links to other chemical databases, we adopt InChIKeys that allow identification of chemicals with a short, checksum-like string. STITCH 2.0 connects proteins from 630 organisms to over 74 000 different chemicals, including 2200 drugs. STITCH can be accessed at http://stitch .embl.de/.
Nucleic Acids Research, 2012
To facilitate the study of interactions between proteins and chemicals, we have created STITCH, a... more To facilitate the study of interactions between proteins and chemicals, we have created STITCH, an aggregated database of interactions connecting over 300 000 chemicals and 2.6 million proteins from 1133 organisms. Compared to the previous version, the number of chemicals with interactions and the number of high-confidence interactions both increase 4-fold. The database can be accessed interactively through a web interface, displaying interactions in an integrated network view. It is also available for computational studies through downloadable files and an API. As an extension in the current version, we offer the option to switch between two levels of detail, namely whether stereoisomers of a given compound are shown as a merged entity or as separate entities. Separate display of stereoisomers is necessary, for example, for carbohydrates and chiral drugs. Combining the isomers increases the coverage, as interaction databases and publications found through text mining will often refer to compounds without specifying the stereoisomer. The database is accessible at
Nucleic Acids Research, 2013
Complete knowledge of all direct and indirect interactions between proteins in a given cell would... more Complete knowledge of all direct and indirect interactions between proteins in a given cell would represent an important milestone towards a comprehensive description of cellular mechanisms and functions. Although this goal is still elusive, considerable progress has been made-particularly for certain model organisms and functional systems. Currently, protein interactions and associations are annotated at various levels of detail in online resources, ranging from raw data repositories to highly formalized pathway databases. For many applications, a global view of all the available interaction data is desirable, including lower-quality data and/or computational predictions. The STRING database (http://string-db.org/) aims to provide such a global perspective for as many organisms as feasible. Known and predicted associations are scored and integrated, resulting in comprehensive protein networks covering >1100 organisms. Here, we describe the update to version 9.1 of STRING, introducing several improvements: (i) we extend the automated mining of scientific texts for interaction information, to now also include full-text articles; (ii) we entirely re-designed the algorithm for transferring interactions from one model organism to the other; and (iii) we provide users with statistical information on any functional enrichment observed in their networks.
Détection spécifique par chromatographie gazeuse-spectrométrie de masse des amines sympathomimétiques urinaires dans le cadre des contrôles antidopage
Journal of Chromatography A, 1991
BMC Bioinformatics, 2007
The increasing protein family and domain based annotations constitute important information to un... more The increasing protein family and domain based annotations constitute important information to understand protein functions and gain insight into relations among their codifying genes. To allow analyzing of gene proteomic annotations, we implemented novel modules within GFINDer, a Web system we previously developed that dynamically aggregates functional and phenotypic annotations of user-uploaded gene lists and allows performing their statistical analysis and mining.
The present paper reports and discusses the results of a 3D finite element simulation of the inje... more The present paper reports and discusses the results of a 3D finite element simulation of the injection molding process of a rubber component, including the stages of the mold filling dynamics and material curing, using the "Reactive Molding" module of the Moldflow 6.2 CAE software. A differential scanning calorimeter (DSC) and a capillary rheometer are employed to characterize the rubber material in order to obtain appropriate curing reaction and viscosity models, respectively. The model parameters so obtained are used to simulate the injection molding process for an engineering rubber component with a complex geometry having a thickness distribution that ranges from 1.5 mm to 20 mm. The computations are found in good agreement with the experimental results, indicating that reliable information on material viscosity and curing kinetic play a key role for well-founded predictions.
Nucleic Acids …, Jan 1, 2011
An essential prerequisite for any systems-level understanding of cellular functions is to correct... more An essential prerequisite for any systems-level understanding of cellular functions is to correctly uncover and annotate all functional interactions among proteins in the cell. Toward this goal, remarkable progress has been made in recent years, both in terms of experimental measurements and computational prediction techniques. However, public efforts to collect and present protein interaction information have struggled to keep up with the pace of interaction discovery, partly because protein–protein interaction information can be error-prone and require considerable effort to annotate. Here, we present an update on the online database resource Search Tool for the Retrieval of Interacting Genes (STRING); it provides uniquely comprehensive coverage and ease of access to both experimental as well as predicted interaction information. Interactions in STRING are provided with a confidence score, and accessory information such as protein domains and 3D structures is made available, all within a stable and consistent identifier space. New features in STRING include an interactive network viewer that can cluster networks on demand, updated on-screen previews of structural information including homology models, extensive data updates and strongly improved connectivity and integration with third-party resources. Version 9.0 of STRING covers more than 1100 completely sequenced organisms; the resource can be reached at http://string-db.org.
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Papers by Andrea Franceschini