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With a design guided by usability studies, the system helps motivate researchers to perform dynamic computational experiments and explore relationships across data sets.

For example, PlasmoDB users seeking novel therapeutic targets may wish to locate putative enzymes that distinguish pathogens from their hosts, and that are expressed during appropriate developmental stages. When a researcher runs one of the approximately searches available on the site, the search is presented as a first step in a strategy. The strategy is extended by running additional searches, which are combined with set operators union, intersect or minusor genomic interval operators overlap, contains.

The interface facilitates interactive adjustment of the component searches with changes propagating forward through the strategy. Users may save their strategies, creating protocols Athens georgia dating free article submission tools today can be shared with colleagues. The strategy system has now been deployed on all EuPathDB databases, and successfully deployed by other projects. The Strategies WDK uses a configurable MVC architecture that Athens georgia dating free article submission tools today compatible with most genomics and biological warehouse databases, and is available for download at code.

The potential for discovery through data mining is governed, in part, by the scale and scope of available data sets, and Athens georgia dating free article submission tools today range of searches available. Many genomics databases support multiple organisms, and integrate a wide range of data sets beyond the genome and gene models. Reference organisms may include curated or automated functional associations, transcript and protein expression data based on many technologiespathway associations, phenotype information, polymorphism data, comparative genomics analyses, protein structure information, cellular location, etc.

Each data type, and each data set, makes additional dimensions available for mining. EuPathDB sites 4 have offered intersect, union and minus operations sincebut until recently users had to go to the Query History page to perform these operations. A simple text box allowed Athens georgia dating free article submission tools today to specify expressions like 1 AND 2 OR 3, which would find the intersection of Results 1 and 2 and union it with Result 3.

While advanced users took advantage of this interface, most ignored it, limiting themselves to simple Athens georgia dating free article submission tools today. This raised the challenge of designing a graphical interface that helps users manage the breadth of available searches and encourages them to combine the search results.

Our solution is a configurable web framework for database searching called the Strategies Web Development Kit WDK that includes a new strategies web application Athens georgia dating free article submission tools today its graphical user interface Figure 1. It is a mature system that has been in production sincewith the new GUI in production since June The top panel shows a strategy with a succession of gene searches strategy steps proceeding from left to right, combined using set operators e.

Steps 2 and 4 are nested steps, indicated by an overlapping Athens georgia dating free article submission tools today icon with colored border.

Introduction

They are expanded as sub-strategies in the indented panels below, where their component steps are visible. Step 3 is a transform expanding the results from Step 2 to include orthologous genes.

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Strategies may be named and saved Athens georgia dating free article submission tools today future reference, refinement, or sharing with others. The bottom half of the display is the summary table which shows a page of results, where each row is one gene found. By default this display shows the result of the strategy as a whole the last step so farbut clicking on any step box or Venn diagram highlights that box in yellow and shows the intermediate result at that point.

Any of these results are downloadable. The summary table can be customized by adding any of approximately 50 columns, and by sorting, filtering and paging. The Strategies WDK provides users with a richly featured search system on a single web application page. Users remain on that page to run and Athens georgia dating free article submission tools today with all active searches.

An initial search becomes the first step of a Strategy, and additional searches are added as needed to extend the strategy refining Athens georgia dating free article submission tools today final result.

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Formally, the strategy can be represented as a tree, where the leaves are searches, and internal nodes are parameterized operations that combine or transform results.

In the display, strategies are shown as linear, but may be nested see belowallowing strategies to be arbitrarily complex. This is convenient for users who want to run a simple search, for those who start simple and realize that refining their search will yield more precise results or for users who have devised a complex plan for data mining. By way of example, a user may wish to identify Plasmodium genes that could be involved in modulating host cell signaling pathways: The user begins a search from toolbar Athens georgia dating free article submission tools today menus or menus on the home page, and is offered a large set of searches organized by type to facilitate navigation.

Each search is orthogonal to the others, and returns records of a single type.

In fact, the strategy of...

Searches are designed by the installer; see System Design and Installation below. Results are automatically displayed Athens georgia dating free article submission tools today the strategy system. This is what the user sees after running a new search, in this case a search for genes by GO term.

The user clicks the Add Athens georgia dating free article submission tools today button red to add another search to the strategy. Doing so pops up the Add Step dialog box presenting a menu of options for the next step Figure 3 a. The user will typically run another search, choosing from among all searches available on the site.

In this example, Athens georgia dating free article submission tools today user has opted to search for Genes based on the presence of Transmembrane TM domains one of several subcellular localization queriesand the appropriate search form Athens georgia dating free article submission tools today appears in the Add Step dialog box Figure 3 b. The user specifies the parameters for the search and, at the bottom of the display, chooses a Venn diagram indicating how this new step should be combined with the accrued results from previous steps.

Figure 3 c shows the combined result 77 genes in the example shown. Adding steps to build a more complex strategy. Clicking on the Add Step button Fig. This brings up a display showing parameters for that search b, top and options for combining with the previous step bbottom. The new step is added to the Athens georgia dating free article submission tools today cand the combined result highlighted and returned as a list in the Summary Display data not shown.

Results generated from a strategy are updated dynamically as new steps are added, existing steps changed or transformations applied. Clicking on a step highlights that box in yellow, and displays the results of that search in the summary table cf. Clicking on a Venn diagram displays the results of the accrued operations to that point cf.

This allows the user to examine the results of intermediate components in the search strategy, and adjust them if necessary. Figure 4 a shows three steps the user has added a third step to limit the result to genes with EST evidence. Figure 4 c illustrates additional options for improving a strategy.

By allowing such embedded substrategies, the strategies system supports nested set operations. The action menu also provides a revise option, allowing users to adjust the parameters of any step in the strategy, with the updated results propagated forward through the strategy. Other dynamic aspects of the Strategy system allow users to add, remove, sort and reposition columns in the summary table.

PlasmoDB provides approximately 55 attributes that may be displayed as columns for gene results gene length, predicted protein molecular weight, time of maximal expression, etc. For example, the user can limit the view of the result to a selected organism or Athens georgia dating free article submission tools today. The strategy built in the above example is shared.

To view and edit Athens georgia dating free article submission tools today copy of it, go to plasmodb. All searches in PlasmoDB are compatible with the strategies system, including BLAST 6 and motif searches which on many sites are returned as static pages only.

In the WDK, these are treated as searches that Athens georgia dating free article submission tools today be added as steps in a strategy, contributing genes to Athens georgia dating free article submission tools today larger data mining process.

Similarly, transformations such as finding the orthologs of a gene set produce strategy-compatible results. Using interval operations as an alternative to set operations, users can combine search results based on the locations within the genome sequence. Another user might wish to identify SNPs contained within non-protein-coding genes. Yet another might wish to examine divergently transcribed genes, i.

These kinds of operations will be familiar to users of systems such as Galaxy galaxy. Each search also offers the user an optional weight parameter that may be used for sorting. For example, one might choose to apply different weights to different forms of expression evidence, weighting protein-level expression most highly e. In the final result, genes supported by all of these searches would have a weight of 60, those found only by protein expression will have a weight of Athens georgia dating free article submission tools today and those supported only by SAGE tag evidence Sorting by weight allows the user to identify the best candidates, even if no candidate is supported by all lines of evidence.

The user can apply a large number of filters without reducing the resulting set to zero: In contrast, the intersection operation can result in overfiltering, and lost candidates.

A similar system is used for target prioritization by the TDR Targets database tdrtargets. A basket Athens georgia dating free article submission tools today allows users to collect individual records or set of records by clicking on a distinctive basket icon, which accompanies IDs displayed throughout the interface cf. Records in the basket can be downloaded as a report, operated on using analysis tools e. The favorites feature lets users hand-select individual records for quick Athens georgia dating free article submission tools today. Strategies can be named, saved and shared with others using a unique URL.

Strategies are saved by default, providing users who have logged in with a permanent record of their query history, except for those that they choose to delete.

Saved strategies can be embedded as modules in other strategies. Using a larger number of steps and substrategies, researchers can develop very specific search strategies. The advanced strategy in Figure 1 finds genes that are candidate drug targets in the malaria parasite, Plasmodium falciparum. The top panel is the main strategy, and the lower panels are the substrategies nested into Steps 2 and 4, respectively. Step 1 identifies genes from any Plasmodium species annotated with an EC number [The Enzyme Commission number is a numerical classification scheme for enzymes, based on the chemical reactions they catalyze 9 ], i.

Because kinases are under-represented in EC annotation, it is unioned with Step 2 which is a substrategy that further searches for kinases. The result after Step 2 is Plasmodium genes with evidence of being an enzyme or specifically a kinase. By selecting that result, the user would see that of those genes are from P.

Step 3 is an ortholog transform that finds P.

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The result is P. Step 4 is another substrategy. In its panel, the user has unioned genes showing differential expression in any of four experiments mass spectrometry, glass slide, microarray and RNA-seq from the trophozoite life cycle stage, when the parasite is most vulnerable to drugs.

While Athens georgia dating free article submission tools today visible in the panel, each of these steps has been given a weight. The mass spectrometry search has a weight of 30, Athens georgia dating free article submission tools today the others have a weight of The Athens georgia dating free article submission tools today operation sums weights, so genes with multiple lines of expression evidence will have higher weights in the final result.

Step 6 uses an orthology-based phylogenetic profile search to keep only genes that are present in the parasite but not in humans, to ensure that the drug does not harm the host. In the final result shown in the summary table, there are 48 genes ordered by their weight, i.

In sum, they are an inclusive set of enzymes and kinases with significant expression in a vulnerable life stage that are essential to the parasite yet absent in the host.

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