InteractiVenn: a web-based tool for the analysis of sets through Venn diagrams

Background

Set comparisons permeate a large number of data analysis workflows, in particular workflows in biological sciences. Venn diagrams are frequently employed for such analysis but current tools are limited.

Results

We have developed InteractiVenn, a more flexible tool for interacting with Venn diagrams including up to six sets. It offers a clean interface for Venn diagram construction and enables analysis of set unions while preserving the shape of the diagram. Set unions are useful to reveal differences and similarities among sets and may be guided in our tool by a tree or by a list of set unions. The tool also allows obtaining subsets’ elements, saving and loading sets for further analyses, and exporting the diagram in vector and image formats. InteractiVenn has been used to analyze two biological datasets, but it may serve set analysis in a broad range of domains.

Conclusions

InteractiVenn allows set unions in Venn diagrams to be explored thoroughly, by consequence extending the ability to analyze combinations of sets with additional observations, yielded by novel interactions between joined sets. InteractiVenn is freely available online at: www.interactivenn.net.     

一个生物网络比对的启发式算法

随着各种高通量生物实验技术的发明和广泛应用,越来越多的分子生物网络数据被公布.有效而且可靠的比对这些网络对检测分子生物网络的保守性功能模块和推测物种间的进化关系有着十分重要的意义.然而,由于网络比对在理论上是NP-困难（nondeterministic polynomialtime-hard）问题,它已经成为当前计算生物学需要攻克的主要难点之一.本文提出了一个比对两个蛋白质相互作用网络的启发式算法.该算法首先通过比较两个网络中所有顶点的邻域相似性给出这两个网络的顶点相似性矩阵,然后利用该矩阵将全局网络比对问题转化为一个二部图匹配问题.众所周知,二部图匹配问题具有多项式时间复杂度算法,本文利用ILOG CPLEX软件进行求解.为了验证该算法的优越性,作者比对了水痘病毒（varicella-zoster,VZV）和卡波济（氏）肉瘤病毒（kaposi＇s sarcomaassociated herpesvirus,KSHV）的蛋白质相互作用网络,并且把比对结果同其它网络比对算法进行比较.结果证明该算法显著提高了全局网络比对的精确度.     

Design and analysis of drug combination experiments

In this paper we present and discuss a novel, simple and easy to implement parametric modeling approach to assess synergy. An extended three parameter log-logistic model is used to analyse the data and calculate confidence intervals of the interaction indices. In addition the model corrects for the bias due to plate-location effects. The analysis is performed with PROC NLMIXED and SAS-code is provided. The approach is illustrated using data coming from an oncology study in which the inhibition effect of a combination of two compounds is studied using 96-well plates and a fixed-ratio design.     

Pro-oxidative effect of beta-carotene and the interaction with flavonoids on UVA-induced DNA strand breaks in mouse fibroblast C3H10T1/2 cells

It has been suggested that β-carotene itself is unstable under certain conditions and that a combination of antioxidants may prevent the pro-oxidative effects of β-carotene. Thus, the present study aimed to investigate the interaction of β-carotene with three flavonoids—naringin, rutin and quercetin—on DNA damage induced by ultraviolet A (UVA) in C3H10T1/2 cells, a mouse embryo fibroblast. The cells were preincubated with β-carotene and/or flavonoid for 1 h followed by UVA irradiation, and DNA damage was measured using comet assay. We showed that β-carotene at 20 μM enhanced DNA damage (by 35%; P<.05) induced by UVA (7.6 kJ/m²), whereas naringin, rutin and quercetin significantly decreased UVA-induced DNA damage. When each flavonoid was combined with β-carotene during preincubation, UVA-induced cellular DNA damage was significantly suppressed and the effects were in the order of naringin≥rutin>quercetin. The flavonoids decreased UVA-induced oxidation of preincorporated β-carotene in the same order. Using electron spin resonance spectroscopy, we showed that the ability of these flavonoids to quench singlet oxygen was consistent with protection against DNA damage and β-carotene oxidation. All three flavonoids had some absorption at the UVA range (320–380 nm), but the effects were opposite to those on DNA damage and β-carotene oxidation. Taken together, this cell culture study demonstrates an interaction between flavonoids and β-carotene in UVA-induced DNA damage, and the results suggest that a combination of β-carotene with naringin, rutin or quercetin may increase the safety of β-carotene.     

Interaction of pathogenic fungi with host cells: Molecular and cellular approaches

This review provides an overview of several molecular and cellular approaches that are likely to supply insights into the host-fungus interaction. Fungi present intra- and/or extracellular host-parasite interfaces, the parasitism phenomenon being dependent on complementary surface molecules. The entry of the pathogen into the host cell is initiated by the fungus adhering to the cell surface, which generates an uptake signal that may induce its cytoplasmatic internalization. Furthermore, microbial pathogens use a variety of their surface molecules to bind to host extracellular matrix (ECM) components to establish an effective infection. On the other hand, integrins mediate the tight adhesion of cells to the ECM at sites referred to as focal adhesions and also play a role in cell signaling. The phosphorylation process is an important mechanism of cell signaling and regulation; it has been implicated recently in defense strategies against a variety of pathogens that alter host-signaling pathways in order to facilitate their invasion and survival within host cells. The study of signal transduction pathways in virulent fungi is especially important in view of their putative role in the regulation of pathogenicity. This review discusses fungal adherence, changes in cytoskeletal organization and signal transduction in relation to host-fungus interaction.     

Role of intramolecular interaction in connexin50: mediating the Ca2+-dependent binding of calmodulin to gap junction

Gap junction channels formed by connexin50 (Cx50) are critical for maintenance of eye lens transparency. Cleavage of the carboxyl terminus (CT) of Cx50 to produce truncated Cx50 (Cx50trunc) occurred naturally during maturation of lens fiber cells. The mechanism of its altered properties is under confirmation. It has been suggested that calmodulin (CaM) participates in gating some kinds of gap junction. Here, we performed confocal colocalization and co-immunoprecipitation experiments to study the relationships between Cx50 and CaM. Results exhibited that the CaM could colocalize Ca2+ dependently with CT in the linear area of cell-to-cell contact formed by Cx50trunc, while it could not localize in the linear area without expression of CT. Further study indicated that the CT could interact Ca2+ independently with the cytoplasmic loop (CL) of Cx50. These data put forward the importance of Ca2+-independent intramolecular interaction between CT and CL of Cx50, which mediate the Ca2+-dependent binding of CaM to Cx50. These intra- and intermolecular interactions may further improve our understanding of biological significance of the Cx50 in the eye lens.     

Parkin interacts with the proteasome subunit alpha4

Mutations in the parkin gene encoding an E3 ligase are responsible for autosomal recessive Parkinson's disease. Putative parkin substrates and interacting partners have been identified, but the molecular mechanism underlying parkin-related neurodegeneration is still unclear. We have identified the 20S proteasomal subunit alpha4 (synonyms: PSMA7, XAPC7, subunit alpha type 7) as a new interacting partner of parkin. The C-terminal IBR-RING domain of parkin and the C-terminal part of alpha4 were essential for the interaction. Biochemical studies revealed that alpha4 was not a substrate for parkin-dependent ubiquitylation. Putative functions of the interaction might therefore be substrate presentation to the proteasome or regulation of proteasomal activity. Full-length parkin and parkin lacking the N-terminal ubiquitin-like domain slightly increased the proteasomal activity in HEK 293T cells, in line with the latter hypothesis.