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Network analysis provides deep insight into real complex systems. Revealing the link between topological and functional role of network elements can be crucial to understand the mechanisms underlying the system. Here we propose a Cytoscape plugin (GIANT) to perform network clustering and characterize nodes at the light of a modified Guimerà-Amaral cartography. This approach results into a vivid picture of the a topological/functional relationship at both local and global level. The plugin hasdoi:10.1371/journal.pone.0105001 pmid:25275465 pmcid:PMC4183485 fatcat:o2jztlpm3zfxffnbczwd6zeybu
more »... en already approved and uploaded on the Cytoscape APP store.
Background Currently, no proven effective drugs for the novel coronavirus disease COVID-19 exist and despite widespread vaccination campaigns, we are far short from herd immunity. The number of people who are still vulnerable to the virus is too high to hamper new outbreaks, leading a compelling need to find new therapeutic options devoted to combat SARS-CoV-2 infection. Drug repurposing represents an effective drug discovery strategy from existing drugs that could shorten the time and reducedoi:10.1186/s12859-021-04076-w pmid:33757425 pmcid:PMC7987121 fatcat:tye4y7z6bzdw3lc6ixvqolih4q
more »... e cost compared to de novo drug discovery. Results We developed a network-based tool for drug repurposing provided as a freely available R-code, called SAveRUNNER (Searching off-lAbel dRUg aNd NEtwoRk), with the aim to offer a promising framework to efficiently detect putative novel indications for currently marketed drugs against diseases of interest. SAveRUNNER predicts drug–disease associations by quantifying the interplay between the drug targets and the disease-associated proteins in the human interactome through the computation of a novel network-based similarity measure, which prioritizes associations between drugs and diseases located in the same network neighborhoods. Conclusions The algorithm was successfully applied to predict off-label drugs to be repositioned against the new human coronavirus (2019-nCoV/SARS-CoV-2), and it achieved a high accuracy in the identification of well-known drug indications, thus revealing itself as a powerful tool to rapidly detect potential novel medical indications for various drugs that are worth of further investigation. SAveRUNNER source code is freely available at https://github.com/giuliafiscon/SAveRUNNER.git, along with a comprehensive user guide.
The time of initiation of antiretroviral therapy in HIV-1 infected patients has a determinant effect on the viral dynamics. The question is, how far can the therapy be delayed? Is sooner always better? We resort to clinical data and to microsimulations to forecast the dynamics of the viral load at therapy interruption after prolonged antiretroviral treatment. A computational model previously evaluated, produces results that are statistically adherent to clinical data. In addition, it allows adoi:10.1371/journal.pone.0015294 pmid:21203461 pmcid:PMC3009726 fatcat:644beieybbdqboofvzbavvosj4
more »... ner grain analysis of the impact of the therapy initiation point to the disease course. We find a swift increase of the viral density as a function of the time of initiation of the therapy measured when the therapy is stopped. In particular there is a critical time delay with respect to the infection instant beyond which the therapy does not affect the viral rebound. Initiation of the treatment is beneficial because it can down-regulate the immune activation, hence limiting viral replication and spread.
The efficiency of lymph nodes depends on tissue structure and organization, which allow the coordination of lymphocyte traffic. Despite their essential role, our understanding of lymph node specific mechanisms is still incomplete and currently a topic of intense research. Results: In this paper, we present a hybrid discrete/continuous model of the lymph node, accounting for differences in cell velocity and chemotactic response, influenced by the spatial compartmentalization of the lymph nodedoi:10.1186/1471-2105-10-387 pmid:19939270 pmcid:PMC2790470 fatcat:3buxrkbjm5amtnyjsmcvzqkd2m
more »... the regulation of cells migration, encounter, and antigen presentation during the inflammation process. Conclusion: Our model reproduces the correct timing of an immune response, including the observed time delay between duplication of T helper cells and duplication of B cells in response to antigen exposure. Furthermore, we investigate the consequences of the absence of dendritic cells at different times during infection, and the dependence of system dynamics on the regulation of lymphocyte exit from lymph nodes. In both cases, the model predicts the emergence of an impaired immune response, i.e., the response is significantly reduced in magnitude. Dendritic cell removal is also shown to delay the response time with respect to normal conditions.
It is becoming increasingly clear that short and long noncoding RNAs critically participate in the regulation of cell growth, differentiation, and (mis)function. However, while the functional characterization of short non-coding RNAs has been reaching maturity, there is still a paucity of well characterized long noncoding RNAs, even though large studies in recent years are rapidly increasing the number of annotated ones. The long noncoding RNA PVT1 is encoded by a gene that has been long knowndoi:10.1155/2015/304208 pmid:25883951 pmcid:PMC4391155 fatcat:df3nva4qvbbi5eja7fvrwgqsca
more »... ince it resides in the well-known cancer risk region 8q24. However, a couple of accidental concurrent conditions have slowed down the study of this gene, that is, a preconception on the primacy of the protein-coding over noncoding RNAs and the prevalent interest in its neighbor MYC oncogene. Recent studies have brought PVT1 under the spotlight suggesting interesting models of functioning, such as competing endogenous RNA activity and regulation of protein stability of important oncogenes, primarily of the MYC oncogene. Despite some advancements in modelling the PVT1 role in cancer, there are many questions that remain unanswered concerning the precise molecular mechanisms underlying its functioning.
 , phenotype; in section 3, we detail the ceRNA model proposed by Paci et al. ... Figure 3 . 3 Results of Paci et al. model to predict miRNA sponge interactions in breast invasive carcinoma  . ...doi:10.3390/genes9090437 pmid:30200360 pmcid:PMC6162385 fatcat:hkrmpxhfizbbjcdtdhxdrhfzd4
We propose a novel procedure to detect structural motifs shared between two RNAs (a reference and a target). In particular, we developed two core modules: (i) nbRSSP_extractor, to assign a unique structure to the reference RNA encoded by a set of non-branching structures; (ii) SSD_finder, to detect structural motifs that the target RNA shares with the reference, by means of a new score function that rewards the relative distance of the target non-branching structures compared to the referencedoi:10.2174/1574893609666140820224651 fatcat:7yhcxt42fbes3ctqlrfob4ezoy
more »... es. We integrated these algorithms with already existing software to reach a coherent pipeline able to perform the following two main tasks: prediction of RNA structures (integration of RNALfold and nbRSSP_extractor) and search for chains of matches (integration of Structator and SSD_finder).
Acknowledgments Paola De Padova wishes to thank the IMERA (Aix-Marseille University) for the fellowship supporting her work from September 2015 to July 2016. ...arXiv:1606.05919v2 fatcat:dxcxn4oyzvdxrjr7t2awagciju
Multiple sclerosis is an autoimmune disease with a strong neuroinflammatory component that contributes to severe demyelination, neurodegeneration and lesions formation in white and grey matter of the spinal cord and brain. Increasing attention is being paid to the signaling of the biogenic amine histamine in the context of several pathological conditions. In multiple sclerosis, histamine regulates the differentiation of oligodendrocyte precursors, reduces demyelination, and improves thedoi:10.3390/ijms23116347 pmid:35683024 pmcid:PMC9181091 fatcat:okavs7yovrccdoezrxgkkzdzcu
more »... ation process. However, the concomitant activation of histamine H1–H4 receptors can sustain either damaging or favorable effects, depending on the specifically activated receptor subtype/s, the timing of receptor engagement, and the central versus peripheral target district. Conventional drug development has failed so far to identify curative drugs for multiple sclerosis, thus causing a severe delay in therapeutic options available to patients. In this perspective, drug repurposing offers an exciting and complementary alternative for rapidly approving some medicines already approved for other indications. In the present work, we have adopted a new network-medicine-based algorithm for drug repurposing called SAveRUNNER, for quantifying the interplay between multiple sclerosis-associated genes and drug targets in the human interactome. We have identified new histamine drug-disease associations and predicted off-label novel use of the histaminergic drugs amodiaquine, rupatadine, and diphenhydramine among others, for multiple sclerosis. Our work suggests that selected histamine-related molecules might get to the root causes of multiple sclerosis and emerge as new potential therapeutic strategies for the disease.
Glioblastoma, the most malignant brain cancer, contains self-renewing, stem-like cells that sustain tumor growth and therapeutic resistance. Identifying genes promoting stem-like cell differentiation might unveil targets for novel treatments. To detect them, here we apply SWIM -a software able to unveil genes (named switch genes) involved in drastic changes of cell phenotype -to public datasets of gene expression profiles from human glioblastoma cells. By analyzing matched pairs of stem-likedoi:10.1038/s41598-018-26081-5 pmid:29773872 pmcid:PMC5958093 fatcat:qqem4hds3femxmfaumu4ypc7ue
more »... differentiated glioblastoma cells, SWIM identified 336 switch genes, potentially involved in the transition from stem-like to differentiated state. A subset of them was significantly related to focal adhesion and extracellular matrix and strongly down-regulated in stem-like cells, suggesting that they may promote differentiation and restrain tumor growth. Their expression in differentiated cells strongly correlated with the down-regulation of transcription factors like OLIG2, POU3F2, SALL2, SOX2, capable of reprogramming differentiated glioblastoma cells into stem-like cells. These findings were corroborated by the analysis of expression profiles from glioblastoma stem-like cell lines, the corresponding primary tumors, and conventional glioma cell lines. Switch genes represent a distinguishing feature of stem-like cells and we are persuaded that they may reveal novel potential therapeutic targets worthy of further investigation. Glioblastoma multiforme (GBM) is the most aggressive and frequent brain tumor, with a median survival time of only 12-15 months from diagnosis 1-3 . It accounts for 15% of all primary brain tumors, 46% of primary malignant brain tumors and around 60-75% of astrocytomas. The frequency of GBM-which affects more men than womenincreases with age and the tumor becomes more common over age 45 3,4 . GBM shows a high infiltration into the brain parenchyma, making standard therapies (e.g. surgical resection, followed by radiotherapy and chemotherapy with temozolomide) unable to effectively arrest tumor development and progression 5,6 . The GBM mortality rate is extremely high when compared to other cancers such as breast and lung cancer 4 , with the 5-years survival rate achieved for only 5% of patients 7-10 . While GBM remains incurable, current research and clinical trials have contributed to a better understanding of the disease progression and to small improvements in patient outcomes. In particular, several studies identified a subpopulation of GBM cells with radio/chemotherapy-resistant properties that have a role in driving tumor initiation, progression, resistance to treatment, and relapse 11-18 . Due to their abilities of self-renewal, proliferation, and differentiation into multiple lineages, these cells are named glioblastoma stem-like cells (GSCs) or tumor-propagating cells (TPCs) 19 , and are held responsible for carcinogenesis. Stem-like cells are not unique to GBM, but they are present in several other cancers, such as breast, colon, prostate, pancreatic cancer, and melanoma 11, 14,      . The failure to remove these cancer stem-like cells is believed to be one of the main reasons behind the ineffectiveness of current therapies in treating glioblastoma and other cancers 17 . Triggering differentiation of cancer stem-like cells may represent a therapeutic opportunity for glioblastoma. Therefore, it is important to better elucidate the factors that govern their fate. Increasing evidence suggests that cell fate decisions in a variety of cell types can be overridden by the artificial expression of a small set of transcription factors (TFs). A recent study 13 identified 19 neurodevelopmental TFs that are selectively expressed in GSCs to maintain their stem-like phenotype and prevent differentiation. A subset
Background Recently, we developed a mathematical model for identifying putative competing endogenous RNA (ceRNA) interactions. This methodology has aroused a broad acknowledgment within the scientific community thanks to the encouraging results achieved when applied to breast invasive carcinoma, leading to the identification of PVT1, a long non-coding RNA functioning as ceRNA for the miR-200 family. The main shortcoming of the model is that it is no freely available and implemented in MATLAB®,doi:10.1186/s12859-022-04695-x pmid:35524174 pmcid:PMC9073480 fatcat:ejsosekrrfesvdunbglyhmufju
more »... proprietary programming platform requiring a paid license for installing, operating, manipulating, and running the software. Results Breaking through these model limitations demands to distribute it in an open-source, freely accessible environment, such as R, designed for an ordinary audience of users that are not able to afford a proprietary solution. Here, we present SPINNAKER (SPongeINteractionNetworkmAKER), the open-source version of our widely established mathematical model for predicting ceRNAs crosstalk, that is released as an exhaustive collection of R functions. SPINNAKER has been even designed for providing many additional features that facilitate its usability, make it more efficient in terms of further implementation and extension, and less intense in terms of computational execution time. Conclusions SPINNAKER source code is freely available at https://github.com/sportingCode/SPINNAKER.git together with a thoroughgoing PPT-based guideline. In order to help users get the key points more conveniently, also a practical R-styled plain-text guideline is provided. Finally, a short movie is available to help the user to set the own directory, properly.
Additional file 1 This file contains the user guide of MIENTURNET showing how the tool works and how to use it.doi:10.6084/m9.figshare.10251875.v1 fatcat:jkadytb4zrbvlgs3yx7xnm2uuy
In Italy women aged 50-69 are invited for a population-based breast cancer (BC) screening. Physicians, policy makers and patients associations agree on the need to inform women about the benefits and harms in order to permit an informed decision. Decision aids (DA) are an effective way to support people in their decisions about health. This trial aims to assess women's informed choices, according to their health literacy and values, on participating or not in BC screening for the first time.doi:10.1186/s12885-017-3428-9 pmid:28629329 pmcid:PMC5477267 fatcat:5gugknthynbfzm6oqs4ihnaucq
more »... efits, harms and controversies are presented. Methods/design: The impact of the DA will be evaluated in a randomized controlled trial with a two-week follow-up. Women will be randomized via web to DA or a standard brochure. We will invite 8160 women, to obtain a final sample of 816 women. The primary outcome will be informed choice, measured on the basis of knowledge, attitudes and intentions on BC screening. Secondary outcomes are participation rate, satisfaction on information and decisional conflict. Discussion: The web DA will be open-source and implemented on BC screenings and its efficacy for increasing informed choice will be tested. This model could be applied to other healthcare settings, cancer screenings, and public health programs. Trial registration: The protocol for this trial was registered with the Clinicaltrials.gov registry on March 16, 2017: NCT03097653.
The biological role of proteins has been analyzed from different perspectives, initially by considering proteins as isolated biological entities, then as cooperating entities that perform their function by interacting with other molecules. There are other dimensions that are important for the complete understanding of the biological processes: time and location. However a protein is rarely annotated with temporal and spatial information. Experimental Protein-Proteins Interaction (PPI) data aredoi:10.1140/epjp/i2014-14134-y fatcat:vf4uzaecunchxkl52ww4k5nsky
more »... tatic; furthermore they generally do not include transient interactions which are a considerable fraction of the interactome of many organisms. One way to incorporate temporal and condition information is to use other sources of information, such as gene expression data and 3D structural data. Here we review work done to understand the insight that can be gained by enriching PPI data with gene expression and 3D structural data. In particular, we address the following questions: Can the dynamics of a single protein or of an interaction be accurately derived from these data? Can the assembly-disassembly of protein complexes be traced over time? What type of topological changes occur in a PPI network architecture over time? 3.
al., 2014; Paci et al., 2017) , was applied to the transcriptomic data sets of the white-skinned berries described herein. ... Therefore, the SWIM tool (Paci et al., 2017) , used to unveil the switch genes in that investigation, which included the identification of fight-club hubs and the heat cartography approach (Palumbo et ...doi:10.1104/pp.17.00311 pmid:28652263 pmcid:PMC5543946 fatcat:kd4uyaagxrcv7dvahzpjmdxj2u
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