UNIT 8.

AN OVERVIEW OF BIOINFORMATICS
I. TEXT 1. Introduction
Biology is in the middle of a major paradigm shift driven by computing technology. Although it is already an informational science in many respects, the field has been rapidly becoming much more computational and analytical. Rapid progress in genetics and biochemistry research combined with the tools provided by modern biotechnology has generated massive volumes of genetic and protein sequence data. Bioinformatics has been defined as a means for analysing, comparing, graphically displaying, modeling, storing, systemising, searching, and ultimately distributing biological information, which includes sequences, structures, function, and phylogeny. Thus bioinformatics may be defined as a discipline that generates computational tools, databases, and methods to support genomic and postgenomic research. It comprises the study of DNA structure and function, gene and protein expression, protein production, structure and function, genetic regulatory systems, and clinical applications. Bioinformatics needs the expertise from Computer Science, Mathematics, Statistics, Medicine, and Biology.

2. Knowledge Base in Biology

In the last 10 years or so, numerous innovations have seen light and the consequence is the development of a new biological research paradigm, one that is information-heavy and computer-driven. As the genetic information is being made as computerized databases and their sizes are steadily growing, molecular biologists need effective and efficient computational tools to store and retrieve the cognate information such as bibliographic or biological information from the databases, to analyze the sequence patterns they contain and to extract the biological knowledge the sequences have. On the other hand, there is a strong need for mathematical methods and computational techniques for challenging computational tasks such as predicting the three-dimensional structure of the molecules the sequences represent, and to construct evolutionary trees from the sequence data. These tools will also be used to learn basic facts about biology such which sequences of DNA are used to code proteins , which other combinations of DNA are not used for protein synthesis, for greater understanding of genes and how they influence diseases. Biology employs a digital language for represening its information using the four basic alphabets (A, C, G, T). All the chromosomes in an organism' cell have been represented and being identified using these alphabets. The demanding challenge here is to determine how this digital language of the chromosomes is being converted into the three-dimensional and sometimes four-dimensional languages of living and breathing organisms.

3. Information Technology in Biology

As it was found that performing all these above-mentioned tasks manually is nearly impossible due to the massive volumes of biological data and the preciseness of works, it became mandatory to use computers for these purposes. Thus this subject of bioinformatics deals with designing and deploying efficient software tools for accomplishing the above quoted tasks in a fast and precise manner. So, bridging the gap between the real world of biology and precise logical nature of computers requires an interdisciplinary perspective.

4. Software and Hardware Advancements in Biology

The tools of computer science, statistics, and mathematics are very critical for studying biology as an informational science subject. Some of the recent advances happened include improved DNA sequencing methods, new approaches to identify protein structure, and revolutionary methods to monitor the expression of many genes in parallel. The design of techniques able to deal with different sources of incomplete and noisy data has become another crucial goal for the bioinformatics community. In addition, there is the need to implement computational solutions based on theoretical frameworks to allow scientists to perform complex inferences about the phenomena under study. Genomics in the recent past has triggered the development of high-throughput instrumentation for DNA sequencing, DNA arrays, genotyping, proteomics, etc. These instruments have catalyzed a new type of science for biology termed discovery science.

5. Human Genome Project - An Introduction

The Human Genome Project has encouraged a series of paradigm changes to the view that biology is an informational science. The draft of the human genome has given us a genetics parts list of what is necessary for building a human: approximately 35,000 genes, their regulatory regions, a lexicon of motifs that are the building block components of proteins and genes, and access to the human variability that make us each different from one user.

6. Genomes - Discovering Methodology and Study

Discovery science defines all of the elements in a biological system. For example, sequence of the genome, identification and quantitation of all of the mRNAs or proteins in a particular cell type - respectively, genome, transcriptome, and the proteome. Discovery science creates databases of information, in contrast to the more classical hypothesis-driven science that formulates hypotheses and attempts to test them. The high-throughput tools both provide the means for discovery science and can assay how 2

global information sets, for example, transcriptomes or proteomes change as systems are perturbed. The genomes of the model organisms yeast, worm, fly etc., have demonstrated the fundamental conservation among all living organisms of the basic informational pathways. Hence systems can be perturbed in model organisms to gain insight into their functioning, and these data will provide fundamental insights into human biology. From the genome, the information pathways and networks can be extracted to begin understanding their logic of life. Further more, different genomes can be compared to identify similarities and differences in the strategies for the logic of life and these provide fundamental insights into development, physiology and evolution. The first eukaryotic genome that has been fully sequenced and annotated is Saccharomyces cerevisiae. This highly helps to develop biological and computational tools for genomic and postgenomic research. In the era of automated DNA sequencing and revolutionary advances in DNA sequence analysis, the attention of many researchers is now shifting away from the study of single genes or small gene clusters to whole genome analyses. Knowing the complete sequence of a genome is only the first step in understanding how the myriad of information contained within the genes is transcribed and ultimately translated into functional proteins. In the post genomic era, functional genomic and proteomic studies helps to obtain an image of the dynamic cell.

7. System Biology
Biology is a highly informational science. There are mainly two types of biological information.

The information of genes or proteins, which are the molecular machines of life The information of the regularity networks that coordinate and specify the expression patterns of the genes and proteins.

All biological information is hierarchical. Initially DNA will change over to mRNA, which in turn goes to protein. Proteins enacts protein interactions, which creates some informational pathways. These pathways form informational networks, which in turn become cells. Now cells forms networks of cells. Finally an individual is a collection of cells. A host of individuals forms population and a variety of populations becomes ecologies. This evolution brings a primary challenge for researchers and scientists to create tools and mechanisms to capture and integrate these different levels of biological information and integrate it towards gaining insight of their curious functionings. All of these paradigm shift lead to the view that the major challenges for biology and medicine in this new century will be the study of complex systems and the approach necessary for studying these biological complexities. Here comes a viable approach.

i. ii. iii.

iv. v.

Identify all elements, such as sequence of genomes in the system with currently available discovery tools Use current knowledge of the sytem to formulate a model predicting its behavior Perturb the system in a model organism using biological, genetic or environmental perturbations, capture information at all relevant levels, such as DNA, mRNA, protein, protein interactions, etc. and integrate the collected information Compare theoretical predictions and experimental data, carry out additional perturbations to bring theory and experiment into closer apposition, integrate new data into model, Iterate steps iii) and iv) till the mathematical model can predict the structure of the system and its systems or emergent properties given particular perturbations.

8. System Biology - Challenges Ahead

The Integration of technology, biology, and computation. The integration of the various levels of biological information and the modeling . The proper annotation of biological information and its its storage and integration in databases. The inclusion of other molecules, large and small, in the systems approach. The integration imperatives of systems biology presents many challenges to industry and academia.

9. Conclusion
With the confluence of biology and computer science, the computer applications of molecular biology are drawing a greater attention among the life science researchers and scientists these days. As it becomes imperative for biologists to seek the help of information technology professionals to accomplish the ever growing computational requirements of a host of exciting and needy biological problems, the synergy between modern biology and computer science is to blossom in the days to come. Thus the research scope for all the mathematical techniques and algorithms coupled with software programming languages, software development and deployment tools are to get a real boost. In addition, information technologies such as databases, middleware, graphical user interface (GUI) design, distributed object computing, storage area networks (SAN), data compression, network and communication and remote management are all set to play a very critical role in taking forward the goals for which the bioinformatics field came into existence.

10. Biological Database Links

NCBI Home
Established in 1988 as a national resource for molecular biology information, NCBI creates public databases, conducts research in computational biology, develops software tools for analyzing genome data, and disseminates

biomedical information - all for the better understanding of molecular processes affecting human health and disease.

Entrez Search and Retrieval System

Entrez Programming Utilities are tools that provide access to Entrez data outside of the regular web query interface and may be helpful for retrieving search results for future use in another environment.

KEGG: Kyoto Encyclopedia of Genes and Genomes

A grand challenge in the post-genomic era is a complete computer representation of the cell and the organism, which will enable computational prediction of higher-level complexity of cellular processes and organism behaviors from genomic information. Towards this end we have been developing a bioinformatics resource named KEGG, Kyoto Encyclopedia of Genes and Genomes, as part of the research projects in the Kanehisa Laboratory of Kyoto University Bioinformatics Center.

TIGR Gene Indices

The TIGR Gene Index Project is supported in part by funding from the US Department of Energy, Grant #DE-FG02-99ER62852, and the US National Science Foundation, Grant #DBI-9983070. Additional funds are provided by the US National Science Foundation through grants #DBI-9813392 and #DBI9975866.

Gramene: A Comparative Mapping Resource for Grains

Gramene is a curated, open-source, Web-accessible data resource for comparative genome analysis in the grasses. Our goal is to facilitate the study of cross-species homology relationships using information derived from public projects involved in genomic and EST sequencing, protein structure and function analysis, genetic and physical mapping, interpretation of biochemical pathways, gene and QTL localization and descriptions of phenotypic characters and mutations.

MaizeDB
The goals of this project are to provide a central repository for public maize information and present it in a way that creates intuitive biological connections for the researcher with minimal effort as well as provide a series of computational tools that directly address the questions of the biologist in an easy-to-use form.

Barley Genomics
AREAS Of RESEARCH: Barley Genome Mapping , Map-Based Cloning, Molecular Breeding, Mutant Isolation & Characterization, Functional Genomics, BAC Address Calculator, Developmental Mutants.

EMBL European Bioinformatics Institute

The European Bioinformatics Institute (EBI) is a non-profit academic organisation that forms part of the European Molecular Biology Laboratory (EMBL). The EBI is a centre for research and services in bioinformatics. The Institute manages databases of biological data including nucleic acid, protein sequences and macromolecular structures.

A Catalog of Genes for Plant Glycerol Lipid Biosynthesis

The current version of this catalog contains more than 2600 sequence files, many of them with annotation and results of our analysis. This version is updated as of Aug. 1999 and includes essentially all publicly available genomic, cDNA, EST and GSS sequences for 62 plant polypeptides involved in lipid metabolism in higher plant species. An important feature of the catalog are the multiple alignments of amino acid sequences deduced from genomic and EST sequences. This version of the dataset accounts for approximately 70% of the Arabidopsis genome.

Grain Genes: A Small Grains and Sugarcane Database

GBrowse, developed by the GMOD group, is a Genome Browser that provides a wealth of genome annotation for maps in the GrainGenes collection. Users can easily manipulate the view of the chromosome and type of data displayed.

PathDB Pathways
PathDB is a beta level research tool for scientists interested in analyzing their experimental or computational data in the context of biological pathways and networks.

Enzymes and Metabolic Pathways Database

Enzymes and Metabolic Pathways database, EMP, is a unique and most comprehensive electronic source of biochemical data. It covers all aspects of enzymology and metabolism and represents the whole factual content of original journal publications.

Boehringer Mannheim Biochemical Pathways

Roche Applied Science: LightCycler, MagNA Pure LC, Lumi-Imager, PCR

ExPASy Molecular Biology Server

The ExPASy (Expert Protein Analysis System) proteomics server of the Swiss Institute of Bioinformatics (SIB) is dedicated to the analysis of protein sequences and structures as well as 2-D PAGE.

Nucleic Acids Research:2000 Biological Database Issue

Nucleic Acids Research (NAR) publishes the results of leading edge research into physical, chemical, biochemical and biological aspects of nucleic acids and

proteins involved in nucleic acid metabolism and/or interactions. It enables the rapid publication of papers under the following categories: chemistry, computational biology, genomics, molecular biology, RNA and structural biology. A Survey and Summary section provides a format for brief reviews. The first issue of each year is devoted to biological databases, and an issue in July is devoted to papers describing web-based software resources of value to the biological community.

Yeast Protein Database HOME PAGE

Six database volumes of biological information about proteins comprise Incyte's Proteome BioKnowledge Library. Each volume focuses on a different organism important in pharmaceutical research.

Saccharomyces Genome Database

SGD is a scientific database of the molecular biology and genetics of the yeast Saccharomyces cerevisiae, which is commonly known as baker's or budding yeast.
TM

The Breast Cancer Gene Database

A database of genes involved in breast cancer. It is similar to the Tumor Gene Database (below) but limited in scope to those genes involved in human breast cancer and thus will be able to go into greater depth. The criteria for a gene to be included in this database are that it has been shown to be involved in human breast cancer (rather than an animal model) and that there is some evidence that it plays a functional role in the induction or progression of breast cancer.

The Mammary Transgene Interactive Database

This is an interactive database of literature on research designed to target transgene proteins to the mammary gland. Current emphasis is on biotechnology applications. Addition of tumor model and developmental model literature is planned.

The Small RNA database

Small RNAs are broadly defined as the RNAs not directly involved in protein synthesis. These are grouped under three categories: l) Capped small RNAs; 2) Noncapped small RNAs; and 3) Viral small RNAs. Sequences and references are included, and you can do wais searching with a keyword.

The Tumor Gene Database

A database of genes associated with tumorigenesis and cellular transformation. This database includes oncogenes, proto-oncogenes, tumor supressor genes/anti-oncogenes, regulators and substrates of the above, regions believed to contain such genes such as tumor-associated chromosomal break points and viral integration sites, and other genes and chromosomal regions that seems relevant.

II. Vocabulary
Accomplish ['kmpli] v. Analyse ['nlaiz] v. = analyze Analytical [,n'litikl] adj.
= Analytic

Hon thnh, lm xong Phn tch (C tnh/ thuc) phn tch Ch gii, ch thch ng dng, trnh ng dng Th nghim, th nghim, phn tch Thuc th mc, chng mc Thch thc, th thch, nhim v kh khn (Thuc hay c lin quan n) khm hay iu tr bnh, lm sng Cng ngun gc, h hng gn, cng bn cht So snh C s dng my tnh, thuc v khoa hc my tnh Phi hp, sp xp Ch yu, ct yu, quyt nh C s d liu C nhim v, bao gm vic Chng minh, gii thch Trin khai, dn trn S thit k, v Ph bin, gieo rc Thuc con s, k thut s Ngnh kin thc, mn hc, quy tc Hin th, ph by ra, s hin th Phn phi, phn b, phn loi Ni bt, r nt S xc nhn, xc nh Cp thit, cp bch Thc thi, thc hin y S suy ra, kt lun S i mi, s cch tn S thu hiu, hiu bit su sc Kt hp, ho hp, hp nht Gi thuyt, l thuyt S thnh tho, s tinh thng Trch, trch xut, chit ra 8

Annotate ['nouteit] v. Application [,pli'kein] n. Assay ['sei] n. v. Bibliographic [,bibli'grfik] adj. Challenge ['tlind] n. Clinical ['klinikl] adj. Cognate ['kgneit] adj. Compare [km'pe] v. Computational [kmpju:'teinl] adj. Co-ordinate [kou':dineit] v. Crucial ['kru:l] adj. Database ['deitbeiz] n Deal (with) v. Demonstrate ['demnstreit] v. Deploy [di'pli] v. Designing [di'zaini] n. Disseminate [di'semineit] v. Digital ['diditl] adj. Discipline ['disiplin] n. Display [dis'plei] v., n. Distribute [dis'tribju:t] v. Emergent [i'm:dnt] Identification [ai,dentifi'kein] n. Imperatives [im'pertiv] Adj. Implement ['implimnt] v. Inference ['infrns] n. Innovation [,inou'vein] n. Insight ['insait] n. Integrate ['intigreit] v. Hypothesis [hai'pisis] n. Expertise [,eksp'ti:z] n. Extract ['ekstrkt - iks'trkt] v.

Framework ['freimw:k] n. Mandatory ['mndtri] adj. Manually ['mnjulli] adv. Middleware ['midl'wer] n. Model ['mdl] v., n. Monitor ['mnit] v. Network ['netw:k] Paradigm ['prdaim] n. Perturb [p't:b] v. Phylogeny [fai'ldni] n.
=phylogenesis [,fail'dineisis]

Khun kh; c cu t chc, ct li C tnh bt buc (Lm g ) bng tay, th cng Middleware is a computer software that connects software components or applications. Phn kt ni trung gian. M hnh ho, m hnh, kiu mu Gim st, ch huy Mng li, h thng H c s l thuyt (ca mt mn khoa hc), nn tng Lm xo trn, lm ri tung ln S pht sinh loi, chng loi pht sinh Tin on, d bo Xc nh s lng, nh lng (c tnh) iu khin, iu ho Ly li, khi phc li, gi ra (thng tin c lu tr) Tm kim, s tm kim nh r, ch r Thng k hc S d tr, ct tr, kho H thng ho, sp xp theo h thng Nhim v, ngha v Thuc/c tnh l thuyt Sn lng, nng sut Tnh bin thin, tnh hay thay i

Predict [pri'dikt] v. Quantitation ['kwntitn] Regulatory [regju:'leitri] adj. = regulator [regju:'leit] Retrieve [ri'tri:v] v. Search [s:t] v., n. Specify ['spesifai] v. Statistics [st'tistiks] n. Storing [st:] n. = store, repository Systemize ['sistmaiz] v.
= systematize ['sistmtaiz]

Task [t:sk] n. Theoretical [,i'retikl] adj. Throughput ['ru:put] n. = Output or production Variability [,veri'bilti] n.

III. READING COMPREHENSION QUESTIONS

1. What is bioinformatics? 2. What can molecular biologists do with effective and efficient computational tools nowadays? 3. Why is it mandatory to use computers in modern lifescience studies? 4. How is biological information classified? 5. Which biological database link do you like most? Why?

IV. GRAMMAR: SENTENCE COMBINING SKILLS The Need to Combine Sentences

Sentences have to be combined to avoid the monotony that would surely result if all sentences were brief and of equal length. Part of the writer's task is to employ whatever music is available to him or her in language, and part of language's music lies within the rhythms of varied sentence length and structure. Even poets who write within the formal limits and sameness of an iambic pentameter beat will sometimes strike a chord against that beat and vary the structure of their clauses and sentence length, thus keeping the text alive and the reader awake. This section will explore some of the techniques we ordinary writers use to combine sentences.

Compounding Sentences
A compound sentence consists of two or more independent clauses. That means that there are at least two units of thought within the sentence, either one of which can stand by itself as its own sentence. The clauses of a compound sentence are either separated by a semicolon (relatively rare) or connected by a coordinating conjunction (which is, more often than not, preceded by a comma). And the two most common coordinating conjunctions are and and but. (The others are or, for, yet, and so.) This is the simplest technique we have for combining ideas:

Meriwether Lewis is justly famous for his expedition into the territory of the Louisiana Purchase and beyond, but few people know of his contributions to natural science. Lewis had been well trained by scientists in Philadelphia prior to his expedition, and he was a curious man by nature. Notice that the and does little more than link one idea to another; the but also links, but it does more work in terms of establishing an interesting relationship between ideas. The and is part of the immediate language arsenal of children and of dreams: one thing simply comes after another and the logical relationship between the ideas is not always evident or important. The word but (and the other coordinators) is at a slightly higher level of argument.

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(Please review the rules of comma usage when you combine two independent clauses with a coordinating conjunction.)

Compounding Sentence Elements

Within a sentence, ideas can be connected by compounding various sentence elements: subjects, verbs, objects or whole predicates, modifiers, etc. Notice that when two such elements of a sentence are compounded with a coordinating conjunction (as opposed to the two independent clauses of a compound sentence), the conjunction is usually adequate and no comma is required. Subjects: When two or more subjects are doing parallel things, they can often be combined as a compounded subject. Working together, President Jefferson and Meriwether Lewis convinced Congress to raise money for the expedition.

Objects: When the subject(s) is/are acting upon two or more things in parallel, the objects can be combined.

President Jefferson believed that the headwaters of the Missouri reached all the way to the Canadian border. He also believed that meant he could claim all that land for the United States. President Jefferson believed that the headwaters of the Missouri might reach all the way to the Canadian border and that he could claim all that land for the United States. Notice that the objects must be parallel in construction: Jefferson believed that this was true and that was true. If the objects are not parallel (Jefferson was convinced of two things: that the Missouri reached all the way to the Canadian border and wanted to begin the expedition during his term in office.) the sentence can go awry. (Please review the principles of parallelism.) Verbs and verbals: When the subject(s) is/are doing two things at once, ideas can sometimes be combined by compounding verbs and verb forms.

He studied the biological and natural sciences. He learned how to categorize and draw animals accurately. He studied the biological and natural sciences and learned how to categorize and draw animals accurately. Notice that there is no comma preceding the "and learned" connecting the compounded elements above.

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In Philadelphia, Lewis learned to chart the movement of the stars. He also learned to analyze their movements with mathematical precision. In Philadelphia, Lewis learned to chart and analyze the movement of the stars with mathematical precision. OR In Philadelphia, Lewis learned to chart the stars and analyze their movements with mathematical precision. (Notice in this second version that we don't have to repeat the "to" of the infinitive to maintain parallel form.) Modifiers: Whenever it is appropriate, modifiers such as prepositional phrases can be compounded.

Lewis and Clark recruited some of their adventurers from river-town bars. They also used recruits from various military outposts. Lewis and Clark recruited their adventurers from river-town bars and various military outposts. Notice that we do not need to repeat the preposition from to make the ideas successfully parallel in form.

Subordinating One Clause to Another

The act of coordinating clauses simply links ideas; subordinating one clause to another establishes a more complex relationship between ideas, showing that one idea depends on another in some way: a chronological development, a cause-and-effect relationship, a conditional relationship, etc.

William Clark was not officially granted the rank of captain prior to the expedition's departure. Captain Lewis more or less ignored this technicality and treated Clark as his equal in authority and rank. Although William Clark was not officially granted the rank of captain prior to the expedition's departure, Captain Lewis more or less ignored this technicality and treated Clark as his equal in authority and rank.

The explorers approached the headwaters of the Missouri. They discovered, to their horror, that the Rocky Mountain range stood between them and their goal, a passage to the Pacific. As the explorers approached the headwaters of the Missouri, they discovered, to their horror, that the Rocky Mountain range stood between them and their goal, a passage to the Pacific.

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When we use subordination of clauses to combine ideas, the rules of punctuation are very important. It might be a good idea to review the definition of clauses at this point and the uses of the comma in setting off introductory and parenthetical elements.

Using Appositives to Connect Ideas

The appositive is probably the most efficient technique we have for combining ideas. An appositive or appositive phrase is a renaming, a re-identification, of something earlier in the text. You can think of an appositive as a modifying clause from which the clausal machinery (usually a relative pronoun and a linking verb) has been removed. An appositive is often, but not always, a parenthetical element which requires a pair of commas to set it off from the rest of the sentence. Sacagawea, who was one of the Indian wives of Charbonneau, who was a French fur-trader, accompanied the expedition as a translator. A pregnant, fifteen-year-old Indian woman, Sacagawea, one of the wives of the French fur-trader Charbonneau, accompanied the expedition as a translator.

Notice that in the second sentence, above, Sacagawea's name is a parenthetical element (structurally, the sentence adequately identifies her as "a pregnant, fifteen-yearold Indian woman"), and thus her name is set off by commas; Charbonneau's name, however, is essential to the meaning of the sentence (otherwise, which fur-trader are we talking about?) and is not set off by a pair of commas.

Using Participial Phrases to Connect Ideas

A writer can integrate the idea of one sentence into a larger structure by turning that idea into a modifying phrase.

Captain Lewis allowed his men to make important decisions in a democratic manner. This democratic attitude fostered a spirit of togetherness and commitment on the part of Lewis's fellow explorers. Allowing his men to make important decisions in a democratic manner, Lewis fostered a spirit of togetherness and commitment among his fellow explorers. In the sentence above, the participial phrase modifies the subject of the sentence, Lewis. Phrases like this are usually set off from the rest of the sentence with a comma.

The expeditionary force was completely out of touch with their families for over two years. They put their faith entirely in Lewis and Clark's leadership. They never once rebelled against their authority.

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Completely out of touch with their families for over two years, the men of the expedition put their faith in Lewis and Clark's leadership and never once rebelled against their authority.

Using Absolute Phrases to Connect Ideas

Perhaps the most elegant and most misunderstood method of combining ideas is the absolute phrase. This phrase, which is often found at the beginning of sentence, is made up of a noun (the phrase's "subject") followed, more often than not, by a participle. Other modifiers might also be part of the phrase. There is no true verb in an absolute phrase, however, and it is always treated as a parenthetical element, an introductory modifier, which is set off by a comma. The absolute phrase might be confused with a participial phrase, and the difference between them is structurally slight but significant. The participial phrase does not contain the subject-participle relationship of the absolute phrase; it modifies the subject of the the independent clause that follows. The absolute phrase, on the other hand, is said to modify the entire clause that follows. In the first combined sentence below, for instance, the absolute phrase modifies the subject Lewis, but it also modifies the verb, telling us "under what conditions" or "in what way" or "how" he disappointed the world. The absolute phrase thus modifies the entire subsequent clause and should not be confused with a dangling participle, which must modify the subject which immediately follows.

Lewis's fame and fortune was virtually guaranteed by his exploits. Lewis disappointed the entire world by inexplicably failing to publish his journals. His fame and fortune virtually guaranteed by his exploits, Lewis disappointed the entire world by inexplicably failing to publish his journals.

Lewis's long journey was finally completed. His men in the Corps of Discovery were dispersed. Lewis died a few years later on his way back to Washington, D.C., completely alone. His long journey completed and his men in the Corps of Discovery dispersed, Lewis died a few years later on his way back to Washington, D.C., completely alone.

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V. PRACTICE
Combining sentences into one: 1. Over the past few decades, major advances in the field of molecular biology have led to an explosive growth in the biological information. The advances in genomic technologies have also contributed to the explosive growth in biological information. The explosive growth in the biological information have been generated by scientific community.

2. A biological database is a large body of persiatent data. A biological database is a organized body of persistent data. A biological database is usually associated with computerized software. The software is designed to update and query components of the data stored within the system. The software is also designed to retrieve components of the data stored within the system.

3. A simple data might be a single file The file contains many records of information. Each of the records includes the same set of information.

4. Molecular modeling may not be as accurate at determining a proteins structure as experimental methods. Molecular modeling is still extremely helpful in proposing and testing various biological hypotheses.

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