SUMMARYOmicCircos is an R software package used to generate high-quality circular plots for visualizing genomic variations, including mutation patterns, copy number variations (CNVs), expression patterns, and methylation patterns. Such variations can be displayed as scatterplot, line, or text-label figures. Relationships among genomic features in different chromosome positions can be represented in the forms of polygons or curves. Utilizing the statistical and graphic functions in an R/Bioconductor environment, OmicCircos performs statistical analyses and displays results using cluster, boxplot, histogram, and heatmap formats. In addition, OmicCircos offers a number of unique capabilities, including independent track drawing for easy modification and integration, zoom functions, link-polygons, and position-independent heatmaps supporting detailed visualization.AVAILABILITY AND IMPLEMENTATIONOmicCircos is available through Bioconductor at http://www.bioconductor.org/packages/devel/bioc/html/OmicCircos.html. An extensive vignette in the package describes installation, data formatting, and workflow procedures. The software is open source under the Artistic–2.0 license.

Analogues of E. coli dihydrofolate reductase (DHFR) containing modified amino acids at single, predetermined sites have been prepared. This was accomplished by the use of the DHFR gene containing an engineered nonsense codon (TAG) at the positions corresponding to Val-10 and Asp-27. Misacylated suppressor tRNAs activated with the modified amino acids of interest were employed for the suppression of the nonsense codons in a cell free protein biosynthesizing system, thereby permitting the elaboration of the desired protein analogues. In this fashion, the aspartic acid analogues erythro-carboxyproline, cysteic acid, β,β-dimethylaspartic acid, α-methylaspartic acid, erythro- and threo-β-methylaspartic acid, N-methylaspartic acid, and phosphonoalanine were incorporated into one or both of the aformentioned positions. Although a number of these analogues were incorporated only in low yield, a modification of the strategy has suggested how this might be improved significantly. The derived proteins were purified and then characterized by their mobility on polyacrylamide gels in comparison with wild-type DHFR. Representative DHFRs modified at position 10 were also degraded by defined proteolysis with Glu-C endoproteinase; the fragments containing the modified amino acids were shown to have the same chromatographic properties on reverse phase HPLC as authentic synthetic standards. Individual analogues were assayed for their abilities to bind to the substrate analogue methotrexate and to convert dihydrofolate to tetrahydrofolate. DHFR analogues containing erythro- and threo-β-methylaspartic acid and β,β-dimethylaspartic acid were all shown to mediate tetrahydrofolate production 74−86% as efficiently as wild-type DHFR under conditions of multiple substrate turnover. Analysis of the rates of tetrahydrofolate production in the presence of NADPH and NADPD at two pH values suggests that this was due to rate-limiting hydride transfer from NADPH bound to DHFR analogues whose active site had been altered structurally.

One of the requirements for a federated information system is interoperability, the ability of one computer system to access and use the resources of another system. This feature is particularly important in biomedical research systems, which need to coordinate a variety of disparate types of data. In order to meet this need, the National Cancer Institute Center for Bioinformatics (NCICB) has created the cancer Common Ontologic Representation Environment (caCORE), an interoperability infrastructure based on Model Driven Architecture. The caCORE infrastructure provides a mechanism to create interoperable biomedical information systems. Systems built using the caCORE paradigm address both aspects of interoperability: the ability to access data (syntactic interoperability) and understand the data once retrieved (semantic interoperability). This infrastructure consists of an integrated set of three major components: a controlled terminology service (Enterprise Vocabulary Services), a standards-based metadata repository (the cancer Data Standards Repository) and an information system with an Application Programming Interface (API) based on Domain Model Driven Architecture. This infrastructure is being leveraged to create a Semantic Service-Oriented Architecture (SSOA) for cancer research by the National Cancer Institute's cancer Biomedical Informatics Grid (caBIG).

A coordinated effort combining bioinformatic tools with high-throughput cell-based screening assays was implemented to identify novel factors involved in T-cell biology. We generated a unique library of cDNAs encoding predicted secreted and transmembrane domain-containing proteins generated by analyzing the Human Genome Sciences cDNA database with a combination of two algorithms that predict signal peptides. Supernatants from mammalian cells transiently transfected with this library were incubated with primary T cells and T-cell lines in several high-throughput assays. Here we describe the discovery of a T cell factor, TIP (T cell immunomodulatory protein), which does not show any homology to proteins with known function. Treatment of primary human and murine T cells with TIP in vitro resulted in the secretion of IFN-gamma, TNF-alpha, and IL-10, whereas in vivo TIP had a protective effect in a mouse acute graft-versus-host disease (GVHD) model. Therefore, combining functional genomics with high-throughput cell-based screening is a valuable and efficient approach to identifying immunomodulatory activities for novel proteins.