Novel Data Fusion Method and Exploration of Multiple Information Sources for Transcription Factor Target Gene Prediction

Background. Revealing protein-DNA interactions is a key problem in understanding transcriptional regulation at mechanistic level. Computational methods have an important role in predicting transcription factor target gene genomewide. Multiple data fusion provides a natural way to improve transcription factor target gene predictions because sequence specificities alone are not sufficient to accurately predict transcription factor binding sites. Methods. Here we develop a new data fusion method to combine multiple genome-level data sources and study the extent to which DNA duplex stability and nucleosome positioning information, either alone or in combination with other data sources, can improve the prediction of transcription factor target gene. Results. Results on a carefully constructed test set of verified binding sites in mouse genome demonstrate that our new multiple data fusion method can reduce false positive rates, and that DNA duplex stability and nucleosome occupation data can improve the accuracy of transcription factor target gene predictions, especially when combined with other genome-level data sources. Cross-validation and other randomization tests confirm the predictive performance of our method. Our results also show that nonredundant data sources provide the most efficient data fusion.Peer reviewe

Regulation of secretion of IL-4 and IgG1 isotype by melatonin-stimulated ovalbumin-specific T cells

In the present study, we describe the potential role of melatonin, a pineal hormone, in regulating the activation of the antigen-specific T cell response. Melatonin encouraged the proliferation of Th cells and improved their ability to secrete IL-4, but down-regulated the levels of IL-2 and interferon-gamma (IFN-γ). Melatonin, however, could not exert any influence on the T cells of unprimed mice. On studying the regulation of subclass of IgG isotype, melatonin specifically enhanced the secretion of antigen-specific IgG1 antibodies and decreased the yield of IgG2a isotype. The results suggest that melatonin possibly acts by selectively activating a Th2-like immune response

Absence of reuptake of serotonin influences susceptibility to clinical autoimmune disease and neuroantigen-specific interferon-gamma production in mouse EAE

Serotonin (5-hydroxytryptamine, 5-HT) is one of the most extensively studied neurotransmitters of the central nervous system. It also has been identified in constituents of the immune system. Therefore serotonin has been suggested to serve as a mediator of bidirectional interactions between the nervous system and the immune system. We investigated this interaction in experimental autoimmune encephalomyelitis (EAE), a well-defined animal model of autoimmune disease of the central nervous system (CNS) mimicking features of the human disease multiple sclerosis. EAE was induced by immunization with the autoantigens myelin basic protein (MBP) or the immunodominant peptide of myelin oligodendrocyte glycoprotein (MOG) spanning amino acids 35–55 (MOGp 35–55). We studied EAE in knockout (KO) mice lacking the 5-HT transporter (5-HTT) on a C57.BL/6 background, in comparison with wild-type C57.BL/6 animals. After immunization with MOGp 35–55, or with rat MBP, the disease courses of the 5-HTT knockout mice were attenuated as compared to wildtype control mice. This difference was more pronounced in female animals. To dissect potential immune mechanisms underlying this phenomenon, histological studies of the CNS and cytokine measurements in mononuclear cells from the spleens of 5-HTT KO mice and wild-type controls were performed. We found a reduction of the inflammatory infiltrate in the CNS and of the neuroantigen-specific production of IFN-γ in splenocytes, again accompanied by a gender difference. These findings suggest a potential role of extracellular 5-HT homeostasis in the fine-tuning of neuroantigen-specific immune responses