10.4 A Genetic Information Model

   

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Let's envision a genetic-based information model. One method of basing our model is to start with a DNA sequence. This base is used by NCBI because GenBank is commissioned as a sequence database as opposed to a protein database such as Swiss-Prot. It is instructive to follow this starting point and see where it leads in terms of the variety of information that can be attached to a sequence that contains a gene. The information model and some of the data within the model will be somewhat contrived to bring out the key points. A detailed and accurate biological model is beyond the scope of this chapter.

Listing 10.1 is an XML document derived from an NCBI DNA sequence entry. For each sequence, a name or definition is provided along with a unique accession number to identify the sequence. This information is contained within the header element; also included in the header element are keywords. Notice how each keyword is contained within its own <keyword> tag. This makes database searching based on keywords much more efficient.

Listing 10.1 DNA Sequence Entry

<dna_sequence_entry>
 <header>
    <definition>
       Human Cu/Zn superoxide dismutase (SOD1) gene
    </definition>
    <accession_no>
       <base_no>L44135</base_no>
       <version>L44135.1</version>
       <GI>1237400</GI>
    </accession_no>
    <keyword>Cu/Zn superoxide dismutase</keyword>
    <keyword>Human SOD1 gene</keyword>
</header>
<source>
    <name>Human Cu/Zn superoxide dismutase (SOD1) gene, exon
    1.</name>
    <organism>Homo sapiens</organism>
    <taxonomy>
       <cell_type>Eukaryota</cell_type>
       <kingdom>Metazoa</kingdom>
       <phylum>Chordata</phylum>
       <subphylum>Vertebrata</subphylum
       <class>Mammalia</class>
       <infraclass>Eutheria</infraclass>
       <order>Primates</order>
       <family>Hominidae</family>
       <genus>Homo</genus>
       <species>sapiens</sapiens>
    </taxonomy>
</source>
<reference>
   <author> Levanon,D. </author>
   <author> Lieman-Hurwitz,J </author>
   <title>
      Architecture and anatomy of the chromosomal locus in human chromosome 21 encoding 
the Cu/Zn superoxide dismutase
   </title>
   <journal> EMBO J. 4 (1), 77-84 (1985)</journal>
  </reference>
  <dna_sequence>
gtaccctgtttacatcattttgccattttcgcgtactgcaaccggcgggccacgccgtgaaaagaag
gttgttttctccacagtttcggggttctggacgtttcccggctgcggggcggggggagtctccggcg
cacgcggccccttggcccgccccagtcattcccggccactcgcgacccgaggctgccgcagggggcg
ggctgagcgcgtgcgaggccattggtttggggcc . . .
 </dna_sequence>
 <features>
    <protein>
       <type>CDS</type>
       <location>1..799</location>
       <gene>SOD1</gene>
       <codon_start>1</codon_start>
       <chromosome>21</chromosome>
       <map>21q22.1</map>
       <product>Cu/Zn-superoxide dismutase</product>
       <protein_id>AAB05661.1</protein_id>
       <db_xref>GI:1237407</db_xref>
       <amino_acid_sequence>
MATKAVCVLKGDGPVQGIINFEQKESNGPVKVWGSIKGLTEGLHGFHVHEFGDNTAGCTSAGPHFNPLSRKHGGPKDEERHVGDL . . .
       </amino_acid_sequence>
    </protein>
 </features>
</dna_sequence_entry>

The next element in Listing 10.1 is source information. This information lets us know where and from what organism the sequence came. For most biologists the hierarchy in Listing 10.2 will be quite familiar.

Listing 10.2 Linnaean Classification of Humans

Kingdom:  Animalia
 Phylum:  Chordata
     Subphylum:  Vertebrata
        Class:  Mammalia
           Subclass:  Theria
              Infraclass:  Eutheria
                   Order:  Primates
                      Suborder:  Anthropoidea
                           Superfamily:  Hominoidea
                                  Family:  Hominidae
                                         Genus:  Homo
                                               Species:  sapiens

Listing 10.2 was taken from one of many Web sites that detail Linnaean classifications (http://anthro.palomar.edu/animal/humans.htm). While the degree of detail expressed in Listing 10.2 (outlining 12 classification categories from kingdom to species) may change depending on the source, it serves to illustrate the natural and efficient mechanism used to classify organisms. We have added acell type category to cover the Eukaryota/Prokaryota breakdown of a cell. Many databases put the primary taxonomic information within a single <taxonomy> tag (Eukaryota to Homo). The inclusion of most of the classification categories within one data item fails to respect the natural hierarchy of Linnaean classification and fails to unleash the strengths of XML. By mapping the natural hierarchical structure into XML, database searches for DNA sequences based on organism classification become more natural and efficient. It is surprising how often this point is missed.

The <reference> element in Listing 10.1 contains journal article information related to the DNA sequence. Often the researcher(s) who sequenced the section of DNA submits a journal article describing the sequence and information related to the sequence. The actual DNA sequence is contained within the <dna_sequence> element.

Finally, Listing 10.1 contains a features section, which contains information about features that are contained within the DNA sequence?in Listing 10.1, a section of the DNA (nucleotides 447 through 1934) code for a protein sequence. Some of the basic information on the protein is contained within the <protein> element.

If life were simple, we could stop here. We may want to add or remove some of the descriptive information about a sequence, but we might be able to lock down a data structure for capturing sequence information. Of course, life is not this simple, and we must consider how we might attach additional information to our base model and what forms this information might come in.

As noted previously, one of the sections in the XML in Listing 10.1 is a features section. In the brief biology introduction (Section 10.2), it was stated that DNA is composed of genes, and genes code for proteins. The feature shown in Listing 10.1 highlights a section of the DNA sequence, nucleotides 447?1934, which is a gene segment that codes for a protein. The protein ID is given along with the protein amino acid sequence. The more one understands and discovers about biology, the more information one would like to attach to the given DNA sequence. Here is a list of a few items that come to mind:

• DNA sequences are composed of genes. The actual gene section (or gene sections if there are multiple genes) of the sequence needs to be identified and noted in the information model (the XML). This would be noted by opening up a <gene> . . . </gene> element within the features section. The gene name, reference number, location, plus other information would be included within the element.

• Genes have promoter sections that control when the given gene is expressed. A gene is expressed if it is actively being transcribed into mRNA. Transcription factors (which are specialized proteins) bind to sections of the DNA in the promoter region to control gene expression and expression rates. The promoter sections need to be identified along with the specific transcription factors that control the gene at hand. Different genes use different transcription factors and different control mechanisms. This implies that, within a gene element, we would have a <promoter> . . . </promoter> element. Within the promoter element, we would have <transcription_factor> . . . </transcription_factor> elements. Within the transcription factor elements, there might be information as to where the promoter section binds with the transcription factor, and under what conditions.

• Genes have regions that code for proteins called exons, and interspersed within the gene may be regions that are not part of the coding for a protein; these regions are called introns. The information model must be able to handle the identification of these sections.

• The same gene may be used to code for multiple different proteins. It is somewhat of a mix and match use of the exon sections of the gene; this is called alternative splicing of the mRNA. Within each gene section, the various proteins that the gene codes for would be inserted. This would move the protein element in the example XML document in Listing 10.1 to be within a gene element. As we learn what control factors determine which proteins are made at which times, these control factors will be added to our model.

• Proteins control almost every biological process in a living organism and are used in the basic structure of organisms. In order to identify what a given gene is controlling or affects, one must know the function of the protein that the gene codes for. A protein function element could be added to the protein element to encode this information.

• A gene may be involved directly in a given organism trait such as eye color, hair color, baldness, number of fingers, and so on. The phenotype of a gene is this outward characteristic expression of the gene. For each gene we may want to have a <phenotype> . . . </phenotype> element. The subelements of the phenotype would depend heavily on the particular gene.

• A gene that goes awry can be the root cause of any number of diseases including sickle cell anemia, Huntington disease, cystic fibrosis, blindness, all kinds of cancers, and so on. A single nucleotide polymorphism (SNP) is a single change in one base-pair on a DNA sequence. Sickle cell anemia is caused by an error in the gene that tells the body how to make hemoglobin. The defective gene tells the body to make the abnormal hemoglobin that results in deformed red blood cells. There is one amino acid substitution, a valine for glutamic acid in the beta sixth position that forms sickle beta chains, which is caused by a SNP on chromosome 11 where the beta chain of hemoglobin is coded. Sections for SNPs and related diseases may be added to capture this information.

Listing 10.3 shows the updated DNA sequence entry with some of this new information added.

Listing 10.3 Updated DNA Sequence Entry

<dna_sequence_entry>
 <header>
    <definition>
       Human Cu/Zn superoxide dismutase (SOD1) gene
    </definition>
    <accession_no>
       <base_no>L44135</base_no>
       <version>L44135.1</version>
       <GI>1237400</GI>
    </accession_no>
    <keyword>Cu/Zn superoxide dismutase</keyword>
    <keyword>Human SOD1 gene</keyword>
 </header>
 <source>
    <name> Human Cu/Zn superoxide dismutase (SOD1) gene, exon
    1.</name>
    <organism>Homo sapiens</organism>
    <taxonomy>
       <cell_type>Eukaryota</cell_type>
       <kingdom>Metazoa</kingdom>
       <phylum>Chordata</phylum>
       <subphylum>Vertebrata</subphylum
       <class>Mammalia</class>
       <infraclass>Eutheria</infraclass>
       <order>Primates</order>
       <family>Hominidae</family>
       <genus>Homo</genus>
       <species>sapiens</sapiens>
    </taxonomy>
 </source>
 <reference>
    <author> Levanon,D. </author>
    <author> Lieman-Hurwitz,J </author>
    <title>
Architecture and anatomy of the chromosomal locus in human chromosome 21 encoding the Cu/
Zn superoxide dismutase
    </title>
    <journal> EMBO J. 4 (1), 77-84 (1985)</journal>
 </reference>
 <dna_sequence>
gtaccctgtttacatcattttgccattttcgcgtactgcaaccggcgggccacgccgtgaaaagaag
gttgttttctccacagtttcggggttctggacgtttcccggctgcggggcggggggagtctccggcg
cacgcggccccttggcccgccccagtcattcccggccactcgcgacccgaggctgccgcagggggcg
ggctgagcgcgtgcgaggccattggtttggggcc . . .
 </dna_sequence>
 <features>
    <gene>
       <location>1..799</location>
       <phenotype>
          <eye_color>blue</eye_color>
       </phenotype>
       <promoter_section>
          <location>100..447</location>
          <transcription_factor>
             Various transcription factor info
          </transcription_factor>
          <transcription_factor>
             Various transcription factor info
          </transcription_factor>
       </promoter_section>
      <SNP>
mutation changing codon 102 from Asp->Gly and causing amyotrophic lateral sclerosis
       </SNP>
       <exon>5</exon>
       <protein>
          <type>CDS</type>
          <location>1..799</location>
          <gene>SOD1</gene>
          <codon_start>1</codon_start>
          <chromosome>21</chromosome>
          <map>21q22.1</map>
          <product>Cu/Zn-superoxide dismutase</product>
          <protein_id>AAB05661.1</protein_id>
          <db_xref>GI:1237407</db_xref>
          <amino_acid_sequence>
MATKAVCVLKGDGPVQGIINFEQKESNGPVKVWGSIKGLTEGLHGFHVHEFGDNTAGCTSAGPHFNPLSRKHGG . . .
          </amino_acid_sequence>
       </protein>
       <related_diseases>
Disease Information, AMYOTROPHIC LATERAL SCLEROSIS Lou Gehrig's disease
      </related_diseases>
    </gene>
 </features>
</dna_sequence_entry>

It would be easy to imagine many more examples of all the possible information that can be associated with one DNA sequence. From this illustration, one quickly begins to realize why biological information is complex to model, and this example touched on only some of the issues at hand. Microbiology is still very much in the discovery phase. It is impossible to predict all of the information, context plus data, that researchers will want to capture against a given sequence. Therefore, it is imperative that the information model be flexible and easily scalable.

A few points about the DNA sequence model presented in Listing 10.3 are worth noting. First, all of the data items are contained within elements and not within attributes. Many of the XML schemas being developed for bioinformatics, and other fields as well, place a variety of their data items within attributes. While this is syntactically correct XML, it is poor information modeling. This practice blurs the distinction between an attribute and a data element. An attribute should tell us how to process or interpret data enclosed within the tag element and apply to all items within the tag element; it should not be data.

The tag structure in the DNA sequence model gives the entire context of related dat The tag structure in the DNA sequence model gives the entire context of related data items. We know based on tag structure, for instance, that "CDS" is a type of a protein coded by a gene that is a feature within a DNA sequence.

Hierarchy is used to show relationships within the model. For instance, a protein is contained within a gene. If the same gene codes for multiple proteins, multiple protein elements will be within the gene element. If the DNA sequence contains several genes, there will be several gene elements, each containing their own protein elements.

Finally, the model represents heterogeneous information, which is not obvious looking at one DNA sequence entry. If we looked across many DNA sequence entries, we would see that each DNA sequence contained different types of information. Some of the basic information types would remain the same; all would have a header element and a <dna_sequence> element, but not all would contain gene elements. This is due to the fact that much of the DNA in humans does not code for proteins and therefore does not contain genes. It is still a mystery what 90 percent of human DNA does! Based on this fact alone, the model must be flexible. Since genes that are in the DNA code for such a wide variety of proteins that are involved in a vast array of functions, it should be clear that the types of information captured for each gene will also vary widely. Therefore, our information model captures heterogeneous information.

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Top Title TOC Preface P.1 What Is XML? P.2 XML Concepts P.3 XML-Related Technologies P.4 XML Data Management P.5 How This Book Is Organized P.6 Who Should Read This Book P.7 Resources Acknowledgments Chapter 8 Chapter 12 Chapter 13 Chapter 14 Chapter 19 Part I: What Is XML? Chapter 1. Information Modeling with XML 1.1 Introduction 1.2 XML as an Information Domain 1.3 How XML Expresses Information 1.4 Patterns in XML 1.5 Common XML Information-Modeling Pitfalls 1.6 A Very Simple Way to Design XML 1.7 Conclusion Part II: Native XML Databases Chapter 2. Tamino-Software AG's Native XML Server 2.1 Introduction 2.2 Tamino Architecture and APIs 2.3 XML Storage 2.4 Querying XML 2.5 Tools 2.6 Full Database Functionality 2.7 Conclusion Chapter 3. eXist Native XML Database 3.1 Introduction 3.2 Features 3.3 System Architecture Overview 3.4 Getting Started 3.5 Query Language Extensions 3.6 Application Development 3.7 Technical Background 3.8 Conclusion Chapter 4. Embedded XML Databases 4.1 Introduction 4.2 A Primer on Embedded Databases 4.3 Embedded XML Databases 4.4 Building Applications for Embedded XML Databases 4.5 Conclusion Part III: XML and Relational Databases Chapter 5. IBM XML-Enabled Data Management Product Architecture & Technology 5.1 Introduction 5.2 Product and Technology Offering Summaries 5.3 Current Architecture and Technology 5.4 Future Architecture and Technology 5.5 Conclusion Notices Chapter 6. Supporting XML in Oracle9i 6.1 Introduction 6.2 Storing XML as CLOB 6.3 XMLType 6.4 Using XSU for Fine-Grained Storage 6.5 Building XML Documents from Relational Data 6.6 Web Access to the Database 6.7 Special Oracle Features 6.8 Conclusion Chapter 7. XML Support in Microsoft SQL Server 2000 7.1 Introduction 7.2 XML and Relational Data 7.3 XML Access to SQL Server 7.4 Serializing SQL Query Results into XML 7.5 Providing Relational Views over XML 7.6 SQLXML Templates 7.7 Providing XML Views over Relational Data 7.8 Conclusion Chapter 8. A Generic Architecture for Storing XML Documents in a Relational Database 8.1 Introduction 8.2 System Architecture 8.3 The Data Model 8.4 Creating the Database 8.5 Connecting to the Repository 8.6 Uploading XML Documents 8.7 Querying the Repository 8.8 Further Enhancements 8.9 Conclusion Chapter 9. An Object-Relational Approach to Building a High-Performance XML Repository 9.1 Introduction 9.2 Overview of XML Use-Case Scenario 9.3 High-Level System Architecture 9.4 Detailed Design Descriptions 9.5 Conclusion Part IV: Applications of XML Chapter 10. Knowledge Management in Bioinformatics 10.1 Introduction 10.2 A Brief Molecular Biology Background 10.3 Life Sciences Are Turning to XML to Model Their Information 10.4 A Genetic Information Model 10.5 NeoCore XMS* 10.6 Integration of BLAST into NeoCore XMS Conclusion Chapter 11. Case Studies of XML Used with IBM DB2 Universal Database 11.1 Introduction 11.2 Case Study 1: "Our Most Valued Customers Come First" 11.3 Case Study 2: "Improve Cash Flow" 11.4 Conclusion Notices Chapter 12. The Design and Implementation of an Engineering Data Management System Using XML and J2EE 12.1 Introduction 12.2 Background and Requirements 12.3 Overview 12.4 Design Choices 12.5 Future Directions 12.6 Conclusion Chapter 13. Geographical Data Interchange Using XML-Enabled Technology within the GIDB System 13.1 Introduction 13.2 GIDB METOC Data Integration 13.3 GIDB Web Map Service Implementation 13.4 GIDB GML Import and Export 13.5 Conclusion Chapter 14. Space Wide Web by Adapters in Distributed Systems Configuration from Reusable Components 14.1 Introduction 14.2 Advanced Concept Description: The Research Problem 14.3 Integration of Components with Architecture 14.4 Example 14.5 Future Generation NASA Institute for Advanced Concepts, Space Wide Web Research, and Boundaries 14.6 Advanced Concept Development 14.7 Conclusion Chapter 15. XML as a Unifying Framework for Inductive Databases 15.1 Introduction 15.2 Past Work 15.3 The Proposed Data Model: XDM 15.4 Benefits of XDM 15.5 Toward Flexible and Open Systems 15.6 Related Work 15.7 Conclusion Chapter 16. Designing and Managing an XML Warehouse 16.1 Introduction 16.2 Architecture 16.3 Data Warehouse Specification 16.4 Managing the Metadata 16.5 Storage and Management of the Data Warehouse 16.6 DAWAX: A Graphic Tool for the Specification and Management of a Data Warehouse 16.7 Related Work 16.8 Conclusion Part V: Performance and Benchmarks Chapter 17. XML Management System Benchmarks 17.1 Introduction 17.2 Benchmark Specification 17.3 Benchmark Data Set 17.4 Existing Benchmarks for XML 17.5 Conclusion Chapter 18. The Michigan Benchmark: A Micro-Benchmark for XML Query Performance Diagnostics 18.1 Introduction 18.2 Related Work 18.3 Benchmark Data Set 18.4 Benchmark Queries 18.5 Using the Benchmark 18.6 Conclusion Chapter 19. A Comparison of Database Approaches for Storing XML Documents 19.1 Introduction 19.2 Data Models for XML Documents 19.3 Databases for Storing XML Documents 19.4 Benchmarking Specification 19.5 Test Results 19.6 Related Work 19.7 Summary Chapter 20. Performance Analysis between an XML-Enabled Database and a Native XML Database 20.1 Introduction 20.2 Related Work 20.3 Methodology 20.4 Database Design 20.5 Discussion 20.6 Experiment Result 20.7 Conclusion Chapter 21. Conclusion References Contributors Editors Chapter 1: Information Modeling with XML Chapter 2: Tamino-Software AG's Native XML Server Chapter 3: eXist Native XML Database Chapter 4: Embedded XML Databases Chapter 5: IBM XML-Enabled Data Management Product Architecture and Technology Chapter 6: Supporting XML in Oracle9i Chapter 7: XML Support in Microsoft SQL Server 2000 Chapter 8: A Generic Architecture for Storing XML Documents in a Relational Database Chapter 9: An Object-Relational Approach to Building a High-Performance XML Repository Chapter 10: Knowledge Management in Bioinformatics Chapter 11: Case Studies of XML Used with IBM DB2 Universal Database Chapter 12: The Design and Implementation of an Engineering Data Management System Using XML and J2EE Chapter 13: Geographical Data Interchange Using XML-Enabled Technology within the GIDB System Chapter 14: Space Wide Web by Adapters in Distributed Systems Configuration from Reusable Components Chapter 15: XML as a Unifying Framework for Inductive Databases Chapter 16: Designing and Managing an XML Warehouse Chapter 17: XML Management System Benchmarks Chapter 18: The Michigan Benchmark: A Micro-Benchmark for XML Query Performance Diagnostics Chapter 19: A Comparison of Database Approaches for Storing XML Documents Chapter 20: Performance Analysis between an XML-Enabled Database and a Native XML Database Remember the name: eTutorials.org Copyright eTutorials.org 2008-2023. 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