Integrated desktop software for management of virus data

FIELD: physics, computer engineering.

SUBSTANCE: invention relates to a system and a method for managing virus data. The system comprises a set of graphical user interface (GUI) tools, including an import tool, an annotation tool, a browsing tool which facilitates representation of types of nucleotides and amino acids, a query tool which facilitates isolation of user-defined genetic characteristics via user-defined annotations associated with sequences, an alignment tool linked to the query tool for selecting one or more query attributes in an alignment function, a genome contig assembling tool, a phylogeny tool which assembles alignments into evolutionary trees, and a mutation analysis tool, and a data storage and retrieval system (DSRS) which is realised in a relational database management system; the DSRS storing genetic, biological, clinical, phenotypical and micro-matrix genome data, and a set of GUI tools for system management in order to manage and analyse data, the set of GUI tools and the DSRS being integrated to manage genome data without data export.

EFFECT: providing fast and flexible management of virus data.

21 cl, 18 dwg

CROSS-REFERENCE TO RELATED APPLICATIONS

This application claims the benefit of provisional application U.S. No. 61/205,033, filed January 14, 2009, the contents of which are incorporated herein by reference.

The LEVEL of TECHNOLOGY

The present invention relates in General to a system and method for managing data on viruses, including data on hepatitis C.

Hepatitis C virus (HCV), in particular, infected about 4 million people in the United States, and it is a major cause of chronic liver disease. Associated with HCV liver disease at the final stage is now one of the leading causes of death among HIV-positive patients. Pathology of HCV includes fibrosis, cirrhosis and hepatocellular cancer. Hepatitis C virus is difficult to explore and it cannot be treated effectively using antiviral drugs, and a favorable response to modern methods of treatment there are less than 50% of cases; to find effective ways will require years.

The HCV particles have a shell and contain the plus-strand of RNA 9 KB. The genome RNA has a single open-reading frames (ORFS)encoding polyblock that proteoliticeski split into a set of 10 clear products (see Figure 1, where the diamonds shows the point of cleavage), which contain the viral particle and the mechanism of viral replication. Netransliruemye the region 5' sends a broadcast LFS GHS through its binding to cellular ribosomes and proteins. HCV infects macrophages and hepatocytes, and, unlike retroviruses, not embedded in the host genome.

Mutations accumulate at sites along the HCV genome, forming hot spots of mutations. These hypervariable sites are concentrated in five areas, which include protein NS5B, the area in and between proteins E1 and E2 and capsid protein. HCV has identified six genotypes and more than 50 subtypes of HCV, which differ from each other by their nucleotide sequences at 31-35%.

Proteins HCV easily mutate, causing resistance to drugs. HCV is clearly a successful pathogen. He has the ability to avoid reactions of the host's immune system, which he does by rapid replication and promotion of mutations through error-prone RNA-dependent polymerase, HCV, which has no ability to correct errors. When HCV infects the patient, the new versions (quasi species changing from one to another in their sequences 1-9%) continuously arise from the dominant infecting genotype during viral replication, giving hundreds of heterologous HCV genomes. The most appropriate of these options are continuously selected in the replication environment on the basis of their ability to replicate and pressures of selection, including all the pressure of antiviral drugs. At some point in time during with the I distribution of quasi species HCV reflects the balance between the continuous creation of new variants, the need to preserve the essential viral functions and positive selection pressures exerted replication environment. Thus, HCV infection creates a complex problem for the production of medicines, as scientists try to track HCV genetic change over time between the transmission of the virus and after treatment, therapeutic means. Infection with HCV is a clear set of problems for analysis. The high mutation rate in HCV leads to the accumulation of huge amounts of new genetic sequences and the corresponding biological data in everyday laboratory studies and clinical trials. Data management is a constant problem. Currently, researchers rely on self-made database, multi-function tools and software from open sources on the Internet to sort, organize and analyze their genomic and biological data. In table 1 (below) presents nine stages, which usually perform for the organization and analysis of data on HCV sequences (left column). In the right column indicates the corresponding program or manual steps that are commonly used to manage these data.

In the Research laboratory researcher, who has a degree, will conduct research and to manage the data that it will receive. Consider a project that includes daily selection of 100 HCV clones for sequencing in the day (i.e. 500-600 clones per week). Daily new sequences are stored on the server, or files in folders on desktop computers, and these sequences is a series of common actions (table 1). It is quite common that data from several days to accumulate and create a very difficult problem to manage, which delay the execution of the project.

Industry tests are often performed on thousands of patients. Blood sampling at 1000-2000 patients per week requires the creation of 1000-2000 sequences per week, or about 200 per day. Management Yes the bag is a real problem. The usual steps that are performed daily on the sequences similar to those in research laboratories (see table 1). Usually running nakaplivaemykh data are one or more people working full-time.

The high rate of mutation results HCV gives a huge amount of new genetic and related biological data in daily laboratory studies and clinical trials with concomitant serious problems with data management. Currently, researchers use self-made database, multi-function tools and software from open sources on the Internet to sort, organize and analyze genomic and biological data. These funds are often associated with particular configurations of hardware or software. These tools are not suitable for use with the HCV genome, and moving data from one program to another requires a lot of effort, time, and error-prone.

DISCLOSURE of INVENTIONS

The present invention relates to a system and method for managing data on the virus, including data on hepatitis C. the System may include software for desktop computer, adapted for fast, efficient and flexible data management the virus is m, including data on HCV. The system can make it easier for scientists to overcome problems associated with data management. Moreover, the system can streamline data management, significantly reducing the time between data collection and definition of treatment method.

The system may consist of a graphical user interface (GUI) and system for storage and retrieval of data (SHPD), which can be specifically designed for the analysis of a particular virus (e.g., HCV). It can also include commercial database engine.

The system can include an annotation tool, which can facilitate the obtaining, holding and managing the critical results of processing of experimental data and to enter the user-defined outcomes (annotations) in the same search context, which already contains a systematic and structured data.

The system may also include means for alignment and phylogeny analysis of mutations that can be specifically adapted to the mathematics of speed replication of the virus (e.g., HCV) and its point of Genesis of mutations (e.g., polymerase, error-prone).

The system may include software architecture, which consists of three layers: the presentation layer (GUI), middleware (subject) and the systems level is the relational database management (RDBMS).

The means for aligning may be associated with a means of presenting the request and enable the tool Assembly of fragments for analysis of complete and partial genomic sequences. Tool for phylogeny may collect alignment in the evolutionary trees that can color code the input sequence and set the timestamps. Graphical tool may present the raw data of electropherogram (traces) and to collect linear and histogram to plot the data by the variables on the graph.

The system may further include means for tracking mutations, reporting and measurement of entropy, and statistical subroutines and security packages and installation.

The system can combine computer science with basic research for rapid detection. The system may contribute to the rapid development of the market of HCV research. As a result the system can greatly improve analytical capabilities and to reduce the processing time. The system can also contribute to basic research in the field of bioinformatics and information theory and give a huge benefit to society.

The system may have a structure of N levels, which allows you to easily scale software among different hardware without it is Timoti replacement funds. For example, the individual levels can be implemented on different machines with different operating systems, thus the whole system will remain capable of communication between them and the efficient processing of the data for viruses.

Various advantages of the present invention will become apparent to experts in this field from the following detailed description of a preferred variant implementation, taken together with the attached drawings.

BRIEF DESCRIPTION of DRAWINGS

Figure 1 - schematic representation of the HCV genome.

Figure 2 - schematic diagram of parts of an example system for data management by viruses.

Figure 3 - schematic diagram of an example of a set of tools for data management by viruses.

Figure 4 - example of architecture of the application.

Figure 5 is an example of the import data.

6 is an example of open data Manager.

7 and 8 hierarchical structure of folders and files.

Fig.9 - box example of the annotation tool.

Figure 10 is an example of the editing screen.

11 is an example of the query design window, and an example of the query results.

Fig - sample window means for sending a request.

Fig is a schematic representation of an example of a tool for alignment.

Fig is a schematic representation of an example of a tool for DNA Assembly to reference.

Fig - schematic represent the effect of sample means for creating a tree phylogenetics.

Fig is a schematic view of a variant example of implementation of the multilevel structure.

Fig is a schematic representation of an example of a tool to view the traces.

Fig is a schematic representation of an example graphical tools.

A DETAILED DESCRIPTION of the PREFERRED OPTION IMPLEMENTATION

Now with reference to Figure 2, there is shown an example system that can solve and overcome the main problems with data management, which are commonly found when working with viruses, such as HCV. The system 10 may consist of 12 graphical user interface (GUI) (e.g., graphical icons and visual indicators that represent the information and actions available to the user), and systems for the storage and retrieval of data (SHPD) 14, and both can be developed specifically for the analysis of HCV or other viruses. The system 10 may also include commercial mechanism 16 relational database (e.g., software component, which can be used to create, search, update, and delete data). These components can allow for the integration, analysis and storage of genetic, biological, clinical and phenotypic data and to provide the ability to request such data (see below).

Means for aligning 20 may be associated with a means for sending a request 26, which may be an existing tool to make a request. Means for aligning 20 may include means for assembling the fragments 28 to assemble the fragments of the genomic sequences in the consensus sequence of the virus (e.g., HCV). Means for aligning 20 can suppress the false predictions of mutations that occur due to technical errors or nevyrovnane, and iteratively improve the alignment of the nucleotide and amino acid sequences (for example, five hypervariable parts of the GHS (see Figure 1), which is split between conservative areas). It can do this with the special pointers sequences and modified algorithms that can calculate the distance based on the cumulative mutations from baseline in these areas. Tool for phylogeny 22 may be intended, among other things, to build these specialized alignments in evolutionary trees, and put colored the odes and time on the input sequences, for example, on the basis of desirable sets of results, for example, according to the quasi-species from the same patient or from samples of clones. Graphical tool 30 may represent raw data electropherogram (traces) and assemble line graphs and bar charts for plotting variables on the graph.

May provide additional tools for tracking the mutations, the measurement of entropy and reporting. The system 10 may also include statistical routines 32 and the security packages and installation. Tool for phylogeny 22, the means 34, 36 for tracking mutations and measurement of entropy and statistical procedures 32 can work together to quantify the degree of change of the virus in sequences of quasi species and, for example, by calculating profiles mutation nucleotide and amino acid sequence diversity), entropy (complexity) and genetic distance (divergence). Means for tracking mutations 34 may be associated with means for phylogeny 22 to determine the speed of the evolution of the types of mutations and the contribution of recombination in a variety of quasi-species and the adaptive evolution of the virus (e.g., HCV) at pressures of the environment.

Statistical routine 32 may form the output of the means for phylogeny 22, the means for tracking mutations and measuring entropie, 36 to calculate the genetic variability of the virus (e.g., HCV). Used in combination with the means to annotate and inquiry 18, 26, these tools 32, 34, 36 may allow researchers to perform critical analyses regarding the sensitivity of the genotype to antiviral drugs, including: 1) the study of the distributions of quasi-species and the destruction of the virus, 2) comparison of genetic heterogeneity among antiviral treatment and eresponder and 3) determining, move whether quasi species of virus (e.g., HCV) resistance mutations within or between genes of the virus in order to increase the diversity of genotypes resistant to the drugs. Statistical routine 32 may also include formulas, for example, to calculate the covariance of the infective genotypes to determine whether a change in the nucleotide or the amino acid in position And mutation or recombination in position In any particular sequence.

The example system 10 may consist of software components that facilitate the storage, integration and analysis of genetic, clinical and phenotypic data and have the ability to request such data. For example, as shown in figure 4, the software architecture may consist of levels 38, 40, 42 views, temporarily the CSOs/logic layer and database when interacting with object layers. For example, these levels may include GUI, middleware and data components. Components of the ISU may include forms (for example, Windows forms)that can be provided to the user with the presentation layer, as a means 12 GUI with which the user can interact with. Components of the ISU can accept user input, and display the results. The components of the middleware may include processing logic (e.g., the methods)used by the system 10 for processing the entered data and return the results to the components of the ISU (for example, objects in the GUI). The components of the middleware (e.g., objects, middleware) can interact with components of the database, for example, through the preparation and transmission of data for storage and retrieval of data in the components database. The database tier may include a system of relational database management (RDBMS) 44 for permanent storage of data and model data. The software architecture is described in more detail below. The input sequences can be easily done through numerous options during a user session. Viral sequences can be entered into the system 10, for example, by any suitable means input, is able to enter a viral sequence or data on viral sequences. Neo is to be understood, that sequence can be entered into the system 10 entirely using tools to import the entire sequence. Example tools to import 45 is shown in the center Figure 5. Tool to import can be configured to allow the input sequences to be imported as raw data or somehow automatically be processed, for example to automatically broadcast or automatically identified. Can be designed suitable means for receiving genetic sequences in the form of separate files, format files FAS or any other suitable data sources. This will allow direct import of data from securitysage device or machine. Sequeira machine can be directly connected to the system or software, or the software may be entered in sequeiros device or machine to work without creating files. This tool can also be designed to receive different types of sequences, such as nukleinovokisly (ntd) or amino acid (AA) sequence. The user can choose genotyping, broadcast and identification of native and partial proteins of the virus (e.g., HCV), using the sequence identifier (see Figure 5). The medium is the translator sequence can transmit data nucleinate sequence in the data on amino acid sequence. The sequence identifier may be in the form of tools, consisting of algorithms used to identify all known genotypes and subtypes of the virus (e.g., HCV). After entering the sequence, the system 10 can automatically calculate the net charge of proteins and mark all the sites of glycosylation and phosphorylation. Genotyping and translation can be presented to the user as options.

Figure 6 shows an example of a tool-data administrator (for example, box 46), which the user can see after entering the sequence. The window 46 of the data administrator can enable the Explorer records 48, which may be flexible organizer 50 according to the type of leaves and nodes of the tree, allowing users to easily work with their data sequences. Users can create a hierarchical structure of folders and files (see Fig.7 and 8), in which they can download a variety of objects, including, without limitation, banks sequences, the results of the alignment marks and the results of the queries.

The system 10 may also have a means to view sequences 51 (for example, a means of displaying and editing, which allows users to view stored sequence). Users can choose to display one or more banks succession is elesta 52. After the display for the selected sequences can be available in various options such as editing, annotating, viewing contained proteins or view nucleotide sites. In the respective Bank can be added new sequence or multiple sequences can be selected for alignment. This is a shared workspace, where users can manipulate the sequences and to view the sequences that are stored in their banks sequences. The system 10 may allow you to use different tools from this and other work spaces.

Selecting the sequence in the viewer 51 (as shown in Fig.6), the user can view the individual proteins identified in the sequence view area/protein 53 (shown in the bottom pane of the window 46 data Manager figure 6). The viewer plot/protein 53 may be capable of displaying the nucleotide and/or protein sequence is segmented into its constituent proteins or parts, respectively. A single sequence can be selected in the viewer sequences to be displayed in this tool. Users can switch to view the protein area and nucleot the underwater area. The system 10 may allow to correlate the parts of the encoding nucleic acids and proteins from raw data. The user can select options in the menu for editing, broadcast, genotyping, annotate, save, or delete sequences that are described in more detail below. Although data Manager 46 may function as a graphical user interface (GUI)through which users can interact with the system, non-graphic data Manager can be implemented separately or in combination with GUI.

User-defined annotations can also be associated with one or more sequences using tools to annotate 18 (see screen annotation 54 at the top right of the window 46 data Manager figure 6). Means for annotating can work as a means of presenting data, user-defined, which allows users to browse and attach the entered data to sequences for reference. Standard and user-defined annotations can be associated with sequences at any time in the session. Screen annotation 54 may allow users to create definitions for the values or text representing clinical, experimental, and/or biological data is e, they would like to associate with their genetic data. This is a user-defined annotation system may allow researchers to easily maintain the confidentiality of the patient and the standards NRA, because they can choose how to store the gathered information.

The user at any time of the session can add annotations to sequences. Annotations that are already defined in the system, can be attached to the sequence for selection elements, as shown in box 55 "Add new annotation" (the right panel in Figure 9). New annotations can be created in the Administrator define annotation 56 (lower panel, figure 9). The user can enter the name of the annotation to define an annotation type from the drop-down menu and select, is there any annotation to the specified values. Examples of embodiments of the system 10 can allow the annotation to take essentially any form, including text, numbers, images, hyperlinks, file Association, or other useful data. The ability to define abstract with great precision allows you to perform complex searches, using the means for sending a request 26.

Users can choose the sequence that they want to annotate, and to do it in the tool to annotate 18, which may be displayed for convenience near what about the means to view the sequence. Annotations can be searched. The administrator define annotation 56 may allow users to use predefined tags and associated data types for annotation configuration (for example, identification data on the patient, type of biopsy, serial, date etc). Means for annotating 18 may also allow users to customize features, such as find and return models in certain positions in the sequence. Means for annotating 18 may, in addition, to allow users to view, add new and edit existing annotations for individual sequences or sets of sequences.

Click on any of the menu items edit sequence from the edit menu 57 (shown in Fig.6), or on the icon editing tools (not shown) may open the desired sequence for editing, broadcast or re-broadcast, genotyping and save. Example tools for editing sequence 57 shown in Figure 10. Means for editing the sequence 57 may allow the user to add and edit data sequence. Click "Next dashes 58 can easily translate the cursor from the dash to the dash, PP the manual I repeat editing. This window may also allow the entry of one sequence by simple insertion sequence in FASTA format (ntd or AA) in the appropriate box. Label sequence FASTA can be automatically inserted into the box Label 59. The relationship of genomic, clinical and experimental data on the virus (e.g., HCV) gives the system 10 additional ability inquiries. An example of a means for sending a request 26 is shown at 11 and 12. Means for sending a request 26 may include a window 60 of the query design window 62 results or report. The window 60 designer allows the user to choose attributes, such as response to treatment, the number of sites of glycosylation and charge sequence. Easily design the queries directed to relational data sets, can help in the identification and correlation of specific viral genetic changes with therapeutic, biological, demographic, and clinical characteristics. Users may select sets of data through user-defined genetic characteristics (to modify the search, identification data section) or through annotations associated with the sequence.

Report on the results of the query can be presented in the results window 62. The results window 62 can provide an easy about the review found data. In the example shown the results window 62 displays the duration of treatment, the result of the reaction and the number of glycosylation sites found for the regions E1 and E2. The results of the query can be aligned with the means for aligning 18 or processed by another tool in the system 10 for advanced analysis. Using the tool to annotate 18, the user can search and annotate the sequences for these special modified sites after the broadcast, which gave the opportunity to make this request.

From the results window 62, the user can request a calculation of the percent change in any position in the alignment. Right-click on the sequence may cause the editing tool 52, so that you can edit the sequence or annotation, or both. The results window 62 can be exported in different formats, for example in the Excel file, or send the tool to align 20 (for example, clicking the right mouse button).

Means for sending a request 26 may allow the user to obtain data about their sequences, limited only by the annotation. This tool can be introduced in a user-friendly index interface to define the query parameters and the output fields for ease of reporting the data sequence. Users can choose from the lists of fields in the standard data structure, but also can search custom fields (annotation), user-defined tool to annotate 18. The query results can be displayed in different formats, for example, in the format with a grid, and can be exported in different formats, such as CVS or FASTA, depending on the case.

Example of the use of tools to query 26 is as follows. The user may want to explore preliminary correlation between viral infectivity and immune function. Proteins of the viral envelope play a major role in tropism, infectivity and immune response of the host cell. The level of positive charge on the HCV E2 can enhance viral infectivity, the number of Proline residues affects the formation of alpha-helix in E2 and, thus, at the entrance of the virus and reduced the number of CD4+ implies decreased immune function and the progression of HCV infection.

To study the above correlation, the user can send a request to the system 10, to: (i) the set of all sequences of E2 with charge AA greater than (>) 4, Number of D4+ 1 to 55 and the number of Proline >20 (see selection panel operator 64 Fig) and (ii) to find data for all sequences E2 AA, charge E2 and quantity the quantity of glycosylation, identification numbers of patients and CD4+ in the result set. This simple query can return a set of results (as shown in the results window 62 on Fig), which allows the researcher to correlate the sequence associated with tropism cells with the progression of the disease. All tasks and the number of special areas, such as sites of glycosylation and phosphorylation may be selected, for example, using the allocator 66 (shown as the bottom panel on Fig). Queries can be saved and annotated. The alignment tool 20 may be associated with means for requesting 18, allowing the alignment to allocate all of the associated attributes of the query.

Now again referring to Figure 4, which shows the junction 40 (i.e. the domain layer, which may consist of several logical layers. In one example, system 10 spanning 40 may include two layers. One is designed to handle domain logic and is called "business rules" 68. This logical layer 68 may be placed between layers of representation and access to data 70 and may be responsible for processing requests from the presentation layer and to him and from the data access layer 70 and to him. All the classes that exist in the business rules 68, can soo is relevant cases to have additional classes in the data access layer. The data access layer 70 may exist between the domain layer logic 68 and RDBMS 44 and may be called "data Access". The data access layer 70 may include all classes responsible for requesting data from RDBMS 44 and presentation of data in it. All the classes that exist in the data access layer 70 may have an additional class in the business layer rule 68, as well as additional tables in the data model 72, described below.

Database (RDBMS) 44 can be used for permanent storage of application data. It can contain system relational database management (RDBMS) third parties and the data model 72. The data model 72 can define table entries, the interdependencies are determined by the primary relationships and relationships foreign keys. Model 72 may contain writing, including sequence, annotation, control sequences, and additional data (reference genotypes, data types, annotations and so on). In one example, the RDBMS 44 can be used free version of Microsoft SQL Server 2005 express.

One example of the above-described system 10 can use the following technique.

Software:

Structure applications: Microsoft ASP .NET

Languages:

VB .Net: Objects view and presenter

# .Net: Objects business rules and data access

C++: the integration algorithms third parties

Form .NET: View

T-SQL: Stored procedures for data collection in the form of a tree

XML: Schematic view of the tree

SQL: DDL and DML

RDBMS (Microsoft SQL Server 2005 Express)

IDE (Microsoft Visual Studio .NET 2005)

Hardware:

Memory: 2 GB DDL Ram

CPU: 1 GHz Pentium

Hard drive: 80 GB 7800 rpm Seagate

As stated above, the system 10 may use N-tier architecture, containing the presentation layers, middleware and systems relational database for persistent storage of data). The presentation layer 38 may consist of components for viewing, such as the ISU 12 (for example, Windows forms), and the presenter classes (e.g., processors for handling events and logical applications. The middleware layer 40 may consist of a main domain layers, such as layer domain logic (i.e. business rules) 68 and the data access layer 70. Scalability, implied this architectural approach can be used so that the system 10 can be scaled to the load without having to change tools. Thus, the system 10 can be easily implemented on multiple computers and multiple operating systems without the need for a significant restructuring of the system 10. The system 10 can be designed using the design pattern of the presenter to view the model(PPM). Software application system can be written mainly in C# .NET (or other appropriate language) and can be divided into three layers, including the user interface (view), application (presenter) and the domain layer (model). Layer the user interface may allow the user form controls Windows and can transmit processing needs through, for example, event handlers, and requests the relevant objects of the presenter. Layer view may not contain processing logic related to objects of the domain layer or application layer. Classes application layer can handle all transfer information to the corresponding classes of view and from them through the interface. Event handlers for the corresponding objects in view may be on the presentation layer. The objects of the presentation layer can handle the delegation of the flow of the application, confirmation of the data entered by the user, the messaging and the query interface of the domain layer. The application layer can accept requests from the auxiliary background services automated test routines regardless of the view. The domain layer can include all classes related to the processing logic requests the information transmitted from the application layer or skip back through the request to the s of the permanent memory. Corresponding objects in the domain layer and the layer of the presenter (e.g., algorithmic processing alignment and get the list of objects to display in the layer view) can be connected to danaperino interface.

Next will be described examples of systems 10 and means 17.

Example tools for sequence alignment in General is listed as item 20 on Fig. Tool for sequence alignment 20 may allow users to place primary DNA, RNA or protein sequences to identify areas of similarity that may be a consequence of functional, structural or evolutionary relationships between the sequences. Alignment can be a tendency to lower accuracy in rapidly mutating viruses, such as HCV. So, may be included algorithms for alignment of the hypervariable sites (for example, five, shown for HCV) separately from scattered conservative sequences along the genome and calculate distances based on aggregate estimates of the combined profile mutation infecting genome (or genomes).

Tool for sequence alignment 20 can allow the user to: a) choose the sequence in the navigation window; (b) to configure the system 10 to automatically distinguish between variants papernov and multiple alignment on the basis of selects whether the user two or more sequences, respectively; (C) to select from a number of suitable algorithms, matrices, quantitative assessment and penalty values of the gap; (d) to choose the suppression of false negative mutations by selecting from the menu polymerase purchased from biotech companies (e.g., TaqMan) (algorithm may include the error rate of the polymerase in the formula); (e) selecting for consideration all or a subset of the five hypervariable sites, in addition to conserved regions for the Assembly; (f) allows for color coding of the various specific data points of the disease (e.g., glycosylation, phosphorylation, mutation or certain user decorating); (g) to view, save, annotate, and export the resulting alignment; (h) collect, edit, and save alignment or replacement; and/or perform other appropriate tasks.

Can be created controls Windows forms user classes of logical fields and the database objects to solve these problems. Users can select a tool to view each sequence that they want to align. After you select more than one sequence in the viewer sequences can be enabled alignment button at the top of viewer sequences which after activation can cause the lift of the panel horizontal separation and loading user control that can be used to collect alignment options. This control may be called, for example, "Designer leveling".

Constructor alignment 73 may have a separated container, which can be divided into two panels, such as left and right. The left panel can contain a list control that can contain a list of labels associated with the selected sequences of tools for viewing sequences. To the right of the list control can be buttons for the image (for example, the up and down arrow buttons)that allow users to reorder the sequence optional (they can also allow the user to define the order in which sequences can appear in the output). The right panel can contain a list of leveling algorithms that can be selected by the user. The list of algorithms may contain the names of the different algorithms is local and complete, pairwise and multiple alignment of protein and/or nucleotide. The list of algorithms can be prepared in accordance with the number of sequences that are aligned (n is an example, if the user selects two sequences, it can be displayed a list of names of available algorithms for pairwise alignment, and if the user selects more than two sequences can be represented by a list of algorithms for multiple alignment). After you select an algorithm from the list below the drop-down list control algorithms may receive a list of options options that may allow users to add parameters that meet the requirements of the selected algorithm (for example, fines for breaks, matrix quantitative assessment etc). The following values of the parameters of the algorithms can be represented by a list of parameters, specific types of mutations or other user-defined parameters, such as controls, color-coded, for example in the form of drop-down lists with fixed controls selection of colors. These parameters can be used by the application to highlight important changes in RNA and amino acid sequences on the screen that appears after alignment. Such mutations may include mutation of RNA, which gives a functional change in the corresponding amino acid, so that the mutation again makes the amino acid order of post-translational modifications (e.g. glycosylation site or factorily the cation), or cause structural changes in the protein. After the user has adequately identified the values of all parameters can be enabled button called "Alignment".

When the user activates this button "Alignment", information on the parameters can be passed to the interface controller 74 through which can be called logical processors domains designed to perform alignment. To complement this process, you can create a control window progress bar. The control window progress bar can contain a progress indicator, control labels (which can display text on the status of progress) and a cancel button, which when activated can interrupt and cancel the current process. Can be created control results 76. The control results may include the display of the output of tools such as management View data grid", and buttons, such as a cancel button and a save button. This control will display for the user aligned sequences. The user can then activate the cancel button to close the control (thus going back to the manage settings or to activate the save button to save the data expressed is nivana. To complement conservation can be created in control. This control can contain a text box control that allows the user to give a name to the tool for alignment and navigation, such as drop-down list of search types to allow the user to specify the folder in Windows Explorer records, which will contain a record of the alignment and will be presented as an icon with the data point labels that are affixed by the user. The user may be able to associate a custom annotation with containers alignment and, if necessary, the ability to search for such objects, using the tool to query.

Example tools for DNA Assembly to reference in General is shown in position 28 on Fig. Tool for DNA Assembly to reference 28 may be one aspect of a tool for aligning 20 or may be implemented separately. Tool for DNA Assembly to reference 28 may collect data fragments from the sequencing projects of any size, from a few to tens of thousands of fragments into a single consensus sequence. Tool for DNA Assembly to reference 28 can be made so as to allow the user to: a) represent fragments of the sequences in the tool 20 alignment for multiple sequence alignment; (b) present controlno the sequence for tools for DNA Assembly to reference, to align the fragments; (C) to develop a draft DNA Assembly to reference in order to identify and remove unreliable data, including the ends of the 3' or 5' of poor quality, the data read subminimal length and vector sequence; (d) to save the resulting consensus sequence and (e) to call a stored sequence for manipulating settings and re-Assembly and/or to perform other related tasks. Can be created controls custom Windows, logical classes of domains and database objects to meet these requirements. Users can choose a set of fragments from the object Bank sequences in Explorer records 48, which may in turn put the saved fragments in the viewer sequences 51. Users can also choose the sequence to use as a reference for alignment. Users can select each sequence in the viewer sequences 51, which they want to use for tools for DNA Assembly to reference 28. After you select more than one sequence in the viewer sequences 51 button designer Contigo may be included at the top of the viewer sequences 51, which after switching on m which can be the cause of the rise of the horizontal bar separating the container and load the user control, which can be designed to determine the parameters of the DNA Assembly to reference. This control may be referred to as "Designer of Contigo". The designer of Contigo 78 may use signs, similar to those of the designer of the alignment, because Kontiki can first be aligned with the control sequence, and then combined into a continuous sequence.

The designer of Contigo 78 may have a separated container, which can be divided into two panels, for example, on the left and right. The left panel can contain a list control that can contain a list of labels associated with the selected tools for viewing sequences, sequences of fragments and the control sequence. To the right of the list control can be buttons for the image (for example, the up and down arrow buttons)that allow users to reorder the sequence optional (they can also allow the user to define the order in which sequences can appear in the pre-Assembly of Contigo, output leveling (scan). The right panel can contain a list of leveling algorithms that can be selected by the user. After you select an algorithm from the list below the drop-down item is the Board a list of algorithms may receive a list of option settings, which can allow users to add parameters that meet the requirements of the selected algorithm (for example, fines for breaks, matrix quantitative assessment etc). Can be installed with the default configuration for optimal alignment of Contigo before assembling (for example, no penalty for end gaps, the high cost of internal breaks, short match with the highest score/balance). The following values of the parameters of the algorithms can be represented by checkboxes. These checkboxes can be associated with additional options prior to Assembly, which the user can choose, for example: a) automatic removal of vector sequence (strongly recommended when using Sanger data); b) removal of contaminating sequences; (C) identification of repetitive sequences; (d) automatic trimming of the ends 5' and 3'; (e) manually set the end; (f) allowing the tool Assembly to optimize the order in which he gathers up the fragments; and/or other relevant options. After the user completes the construction of the Assembly may include a button called "Assembly". When the user activates the button "Build", the information on the parameters can be passed to the interface controller 74 through which may be due lo the practical processors domains to perform multiple alignment and the subsequent Assembly of the consensus sequence. To complement this process, you can create a control window progress bar. The control window progress bar can contain a progress indicator, control labels (which can display text on the status of progress) and a cancel button, which when activated can interrupt and cancel the current process. Can be created in the control 80. The control 80 may include a display output of the means for DNA Assembly to reference 28, such as a text box, the control grid View data"button, such as a cancel button and a save button. In the text field can be entered consensus sequence. The text box can have the ability to scroll (right or left). Tool to view the data grid will contain all of the aligned sequence fragments. The user can then activate the cancel button to close the control (thus returning to the constructor of Contigo) or to activate the save button to save the results tools for DNA Assembly to reference 28. To complement conservation can be created in control. This control can contain a text box control that allows the user to give a name to the tool for you is animania and navigation such as drop-down list of search types to allow the user to specify the folder in Windows Explorer records 48, which will contain a record of the proceedings and will be presented as an icon with the data point labels that are affixed by the user. The user may be able to associate a custom annotation with containers alignment and, if necessary, the ability to search for such objects, using the tool to query 26.

Example tools for phylogeny in General is shown in position 22 on Fig. Tool for phylogeny 22 may collect specialized alignment, which take into account hypervariable sites in the evolutionary tree, and can put color codes and timestamps in the input sequences according to the desirable aspects such as quasi species from one patient or clonal samples. Tool for phylogeny 22 can allow the user to: a) design and perform the multiple alignment, which is described in the steps above; (b) to color code sequences or parts of sequences for easy tracking of quasi species the type of mutation or sites under selective pressure in one patient or clone of wood; (C) to create and graphically display the root trees phylogeny; (d) save the trees in resposne emom format such as PAUP format (*.pau or *.nex); and/or perform other appropriate tasks. Can be generated form controls Windows user, you Can create form controls Windows user classes of logical fields and the database objects to solve these problems. Users can choose the sequence of devices for viewing sequences 51 for design alignment (described above). Right split container constructor alignment 73 may have a button control named "optimize for phylogeny". If the user clicks on this button, alignment options, the default can be entered in the input parameters of the constructor, choosing the alignment algorithm, it is best suitable for construction of the tree phylogeny (for example, ClustalV), and automatically enter the associated control parameter values optimized for constructing phylogeny (see optimizer phylogeny 82 on Fig). Can be created and displayed additional controls parameters (such as color picker for easy tracking of quasi species). After defining all the required alignment options can be activated button "Build a tree". After the user activates the button "Build a tree" is the information on the parameters can be passed to the interface controller 74, through which can be called logical processors domains that are designed to perform multiple alignment and the subsequent Assembly of the tree. To complement this process, you can create a control window progress bar. The control window progress bar can contain a progress indicator, control labels (which can display text on the status of progress) and a cancel button, which when activated can interrupt and cancel the build process tree. Can be created a user control 84 "View tree". This control 84 may be a control that can display the results of the process of constructing the tree. To finish creating this control, you can use the graphics window or other such tools. The option of color coding can be displayed in accordance with the parameters entered by the user (as appropriate). May be available the option to save the results of the build process tree.

The corresponding domain objects can be created, for example, in C#, in order to facilitate the handling of different tools. Domain logic can be divided into categories, for example, business rules 68 and data access 70. Corresponding objects, which treats each part of the various tools can be created at the domain level, for example, one business rule 68 and the other for data access 70.

In the example system, generally shown at position 10 on Fig can be created object business rules called "Alignment" to handle requests on behalf of the additional object application layer, which can also be called "Alignment". You can create a data access object with the name "access to the alignments to handle the communication with the database queries from the domain object "Alignment". Object Alignment" may be composed of properties for getting and setting data inputs from surface alignment properties, which may contain the results of the alignment methods perform alignment or methods that are associated with components of third parties, designed to handle alignments and delivery of results. Object Access alignments may include methods that include DML for a specific RDBMS, which can streamline the storage and retrieval of constant inputs and outputs for the mechanism 44 RDBMS. You can create a business object rules called "Tool for DNA Assembly to reference" to handle requests on behalf of the additional object application layer, also called "Alignment". The data access object with the name "Access to sredstvo for DNA Assembly to reference" can be created to handle the interaction with the database query domain object "Tool for DNA Assembly to reference". Object "Tool for DNA Assembly to reference" may consist of properties for getting and setting data inputs designer related objects, properties that may contain the results of running projects related objects, how to perform alignments or methods that are associated with components of third parties that process alignment and display of the results, and how to build consensus sequence. Object Access alignments can contain methods, which may include DML for a specific RDBMS, which can streamline the storage and retrieval of constant inputs and outputs of the mechanism 44 RDBMS.

Model reference data 72 may include multiple records. In one example, system 10 data model 72 consists of four records. The first record can be called "sequence alignment" and can be used to store the header record sequence alignment. It may contain the following fields: field primary key/identity (UIP), field name (label) and the parameter field/header (params). The second entry can be called "sequence alignment" and can store pointers to individual sequences that are aligned, and the aligned sequence. It may include the primary key/ID (UIP), field externally what about the key (seq_align_uid), UIP-line sequence, which is stored in the table of sequences (sequence_uid), and the field containing the sequence as it appears in the results of the alignment. The third record can be a record header for the session DNA Assembly to reference and may include the primary key/ID (UIP), field name (label) and the parameter field/header (params). The fourth record may contain the results of the alignment of Contigo and can have the following fields: a primary key/ID (UIP), the foreign key field (contig_assembly_uid), UIP-line sequence, which is stored in the table of sequences, and a flag that can be used as an indicator with three States, which indicates to the system whether the sequence is a fragment, a reference or control.

In one example, system 10 object business rules called "the Tree phylogeny, for example, to process requests on behalf of the additional object application layer, also called "the Tree phylogeny". The data access object with the title "Access to the tree phylogeny" can be created to handle the interaction with the database query domain object Tree phylogeny". The object Tree phylogeny" may consist of properties for getting and setting an input surface alignment properties that mightcreate the results of the alignment, how to perform alignments and how to create Finogenova tree (for example, the connection of the neighbors). Object access to the tree phylogeny may include methods that include DML for a specific RDBMS, which can streamline the storage and retrieval of persistent data in RDBMS 44.

Model reference data 72 may contain multiple records. In one example, system 10 model reference data 72 may contain two entries. The first record may be referred to as "alignment filogenia sequence and can be used to store the header record of the initial sequence alignment and the resulting tree. It may contain the following fields: a primary key/ID (UIP), field name (label)of the parameter field/header alignment (alignment_params) and the second parameter field/header (phylo_params).

The second entry may be referred to as "phylogeny sequence and can store pointers to individual sequences, which may represent the initial alignment. It can contain the primary key/ID (UIP), the foreign key field (seq_align_uid), UIP-line sequence stored in the table of sequences (sequence_uid), and a field comprising the sequence as they appear in the results of the preliminary multiple alignment.

Can be developed gr the specific means to aid the researcher in data analysis for HCV. Graphical tools can provide the raw data electropherogram (traces) and assemble line graphs and histograms for drawing on two variables. Graphical tools can allow the user to save and view files traces associated with their sequences, and apply the collected application line graphs and histograms on the two variables.

Custom controls can allow users to perform these tasks. The first control can be a means to view the traces shown in Fig, and the second may be the generator of the graphs shown in Fig. The control forms of Windows can allow users to view files trace chromatograms associated with sequences entered into the system. Tools for editing and adding sequences can be extended to allow you to store files traces. In one example, system 10 control button "Add file traces can be added to the editing control sequence 51. When the user activates this button, you may see a dialog box on the file system that asks the user to select the location of the file traces from the local file system or over the network. After the user is seems the file traces, which should be associated with this sequence, the user can select this file. After this dialog box, the file system can be closed, and the file path traces can be transferred to domain method, which can transfer the contents of the file and the full path to the properties of the sequence that will be saved. The user can then activate the save button to save the data; the sequence can be updated, and the edit window sequence can be closed. String sequence represented in the viewer sequences 51 may be updated to include an icon that indicates that the write sequence includes corresponding file traces. When the user activates the icon may open the viewer window file traces.

The user control with the name "view tracks" 86 may be a control that can read and interpret the file traces. To finish creating this output control can be used graphics window. Can be generated classes to interpret each type of supported files traces (such as ABI and SCF) and colouring sequence (color coding, for example, a nucleotide) and comply with the plans of the graph traces (color coding, for example, a nucleotide). Users can be able to scroll left and right for a full view of the traces.

Custom form controls Windows can allow users to view graphs related to specialized, specific to the virus (e.g., HCV) values custom annotations associated with sequences in the system. Controls in the form of checkboxes can be added in the Explorer panel of the annotations associated with a particular annotation, which can be common to all sequences in the viewer. These annotations may have a common data type. After selecting a General annotation can be activated radio button control with two items of the list, one, for example, marked "line graph", the other marked "histogram" and a button named "view graph". After selecting any item radio buttons and activate the button "view graph might pop up a new window with the title "tool to view the graphs. This window can contain a custom image control that can display the received image graph generated by the system in accordance with the data points together with a total registered value annotations consistently the tee, and an export button that allows the user to save the resulting image in the file system (for export to other programs and formats, such as Excel or PowerPoint).

The corresponding domain objects in C# can expedite the processing of the above means. Domain logic can be divided into categories, for example, business rules 68 and data access 70. Corresponding objects are related to each tool can be created at the domain level, for example, one business rule 68 and the other for data access 70. In one example, system 10 object business rules 68 called "Traces" can be included for processing requests on behalf of the additional object application layer also called "Traces". The data access object can be called "Access tracks and can handle the communication with the database query domain object "Traces" (namely, to conduct the search of the binary data on the tracks in the recording sequence). Object "Traces" domain logic may consist of properties for getting and setting the option for viewing traces (such as color coding nucleotides and iconic waves) and methods for the analysis points binary data and interaction with graphical objects to create visual output traces. Object Access tracks may include the ways in which clucalc DML for a specific RDBMS, which can streamline the storage and retrieval of constant inputs and outputs of the mechanism 44 RDBMS related to the file traces associated with the sequence. The object of the business rules can handle the interpretation of graphs and give the results of this process in the bit image for display and export.

There is a fundamental lack of understanding as numerous variants of the virus (e.g., HCV) affects the genomic response of the host body. To measure this reaction, the researchers study the infected host genome at the level of transcription by analyzing the expression profiles of genes with the use of technology chips. The system 10 may include a database for data chips from, for example, 50,000 transcripts and can associate the sequence of the virus (e.g., HCV) directly to the profile owner's chips. The system 10 can also enable to normalize the data chip chips created by various chemical platforms (e.g., two-colour system, lithographic synthesis and so on). Protein of the virus (e.g., HCV) and files chips associated with the common ID number. The system 10 to maintain the relational hierarchy while preserving the ability of the research. Also, the system 10 may implement the possibility of side due to Paul what the user had a choice, to link or not to link follow-up data on the expression and sequence. Tool for genotyping can identify the genotype and serotype of the input sequence by comparing (e.g., three) small nucleotide domain (e.g., three) parts (for example, "C/E1/NS5B/5'UTR for HCV) viral control sequences specific genotype/serotype with the input genome of the virus. This strategy genotyping based on conservative data Murphy and others (Murphy et al.) (2007), very accurate, recognizes all known serotypes of the virus (for example, n=77 for HCV) and is the newest way to identify the virus in comparison with all others. Means for determining the genotype can use the scheme orientation sequence, which is based on conservative areas, for orientation and identification in the same domain (for example, for NS5B HCV), then a different domain (for example,/E1 for HCV) and to the latest domain name (for example, 5'UTR for HCV). This multi-level (for example, a three-tiered approach to validation may provide approximately 90% accuracy of identification of genotype/serotype. This tool can be easily modified to determine the genotype and serotype other viral sequences.

In this area, it is understood that any of the above elements in the management forms of Windows can be done in various other programming tools and other operating platforms.

In accordance with the provisions of the patent law, the principle and mode of operation of the present invention have been explained and illustrated in the preferred embodiment. However, it should be understood that the present invention can be implemented otherwise than is specifically explained and illustrated, but without breaking his spirit or scope.

1. A system for managing data on viruses, and the system includes:
one or more of graphical user interface (GUI) and system for storage and retrieval of data (SHPD), and SHPD stores genetic, biological, clinical and phenotypic data on viruses, and one or more tools GUI work for the implementation of the management system to manage and analyze data, and one or more tools of the ISU and SHPD integrated data management for viruses without exporting the data.

2. The system according to claim 1, additionally comprising the annotation tool, which manages the annotations in the form of user-defined data points and integrates annotations in the search context, which is an integral part of the system.

3. The system according to claim 1, additionally including the import tool, which automates the task of separating one or more viral sequences for men is our least one of, includes separate proteins and the region.

4. The system according to claim 1, characterized in that at least one of the means of the ISU provides a view of the nucleotides and amino acids and is able to switch between these views.

5. The system according to claim 1, characterized in that at least one of the means of the ISU includes a means for requesting at least one additional tool GUI, and means for sending a request made with the possibility of isolation in a stand-alone set of at least one data set by at least one user-defined genetic characteristics and annotation associated with sequences, and means for sending a request made with the possibility of transfer of an isolated set of at least one additional tool GUI.

6. The system according to claim 5, characterized in that at least one additional tool GUI includes a means for alignment, associated with means for sending a request to allow you to select one or more attributes of the query in the function alignment.

7. The system according to claim 6, characterized in that the means for aligning includes means for DNA Assembly to reference, collects a set of fragments of the genomic sequence of at least one set of viruses detected is the system.

8. The system according to claim 1, additionally comprising means for phylogeny, which collects alignment in the evolutionary trees that encode color and put timestamps on the data series.

9. The system according to claim 1, additionally comprising a graphical tool that presents the raw data electropherogram and collects at least one of a line graph or histogram for application variables on graphs and representations of these graphs.

10. The system according to claim 1, additionally comprising means for sending a request, which binds relational datasets by viruses.

11. The system according to claim 1, additionally comprising means for requesting that selects viral sequence according to the attributes defined by the user, from the list of annotation previously associated with sequences.

12. The system according to claim 11, characterized in that the means for sending a request contains abstracts and statements, which are selected by the user and installed to control the results of the query.

13. The system according to claim 1, additionally comprising a means for aligning the tool for phylogenetics and means for the analysis of mutations, and means for alignment and phylogeny analysis of mutations integrated in one place.

14. The system of item 13, characterized t is m, means for alignment and phylogeny analysis of mutations specifically adapted to the properties of the viral replication of the corresponding virus.

15. The system according to claim 1, having an architecture consisting of three levels, including the presentation layer, the level middleware and database-level interaction with the object layer and the presentation layer contains one or more components of the ISU, including one or more tools, GUI, level middleware contains one or more binder components and includes processing logic used by the system, and the database tier contains one or more data components, including the storage and retrieval of data.

16. The system of clause 15, wherein at least one of the means of the ISU has one or more Windows forms provided to the user presentation layer, and these one or more Windows to accept user input and display output, and processing logic processes the input and returns the output in one or more forms of Windows.

17. The system according to claim 1, additionally comprising means for annotating tool to align the tool for DNA Assembly to reference tool for phylogenetics, a tool for the analysis of mutations, a graphical tool, the tool direction is of queries, means for tracking mutations, means for entropy, the means for data processing chips and a means for determining genotype.

18. The system according to claim 5, characterized in that the means for sending a request made with the possibility to save and annotate the query.

19. A system for managing genomic data, comprising:
the Toolkit graphical user interface (GUI), including import tool, the annotation tool, the viewer, providing a representation of the types of nucleotides and amino acids, the means for requesting, providing isolation of user-defined genetic characteristics through user-defined annotations associated with sequences, a means for aligning, associated with means for sending a request to select one or more attributes of the query in the function of the alignment tool for DNA Assembly to reference genome, the tool for phylogeny, which collects alignment of evolutionary trees, and a tool for the analysis of mutations, and
system for storage and retrieval of data (SHPD)implemented in the management system relational database, and SHPD stores genetic, biological, clinical, phenotypic and micromachine genomic data and tools GUI to implement the Oia system management, to manage the data and analyze the data, and a set of tools GUI and SHPD integrated management of genomic data without exporting the data.

20. A system for managing genomic data, comprising:
system for storage and retrieval of data (SHPD)that stores genetic, biological, clinical, phenotypic and micromachine genomic data, and
one or more of graphical user interface (GUI)that is displayed to the user and process and analyze genomic data through interaction with one or more graphical representations of genomic data in the ISU,
moreover, one or more funds of the ISU and SHPD integrated management of genomic data without exporting the data.

21. The system according to claim 20, additionally comprising sequeiros device for the generation of a set Sequeira data, and SHPD configured to access and store the set Sequeira data.