The gene identification problem: An overview for developers <s> INTRODUCTION <s> Databases: C. Burks et al. , GenBank: Current Status and Future Directions. P. Kahn and G. Cameron, EMBL Data Library. W.C. Barker, D.G. George, and L.T. Hunt, Protein Sequence Database. B. Keil, Cooperation between Databases and Scientific Community. Searching Databases: W.R. Pearson, Rapid and Sensitive Sequence Comparison with FASTP and FASTA. R.F. Doolittle, Searching through Sequence Databases. S. Henikoff, J.C. Wallace, and J.P. Brown, Finding Protein Similarities with Nucleotide Sequence Databases. C.B. Lawrence, Use of Homology Domains in Sequence Similarity Detection. M. Gribskov, R. L~aduthy, and D. Eisenberg, Profile Analysis. Patterns in Nucleic Acid Sequences: R. Staden, Finding Protein Coding Regions in Genomic Sequences. J.C.W. Shepherd, Ancient Patterns in Nucleic Acid Sequences. R. Staden, Searching for Patterns in Protein and Nucleic Acid Sequences. G.D. Stormo, Consensus Patterns in DNA. M.S. Waterman and R. Jones, Consensus Methods for DNA and Protein Sequence Alignment. J.-M. Claverie, I. Sauvaget, and L. Bougueleret, k-Tuple Frequency Analysis: From Intron/Exon Discrimination to T-Cell Epitope Mapping. P. Senapathy, M.B. Shapiro, and N.L. Harris, Splice Junctions, Branch Point Sites, and Exons: Sequence Statistics, Identification, and Applications to Genome Project. Predicting RNA Secondary Structures: J.A. Jaeger, D.H. Turner, and M. Zuker, Predicting Optimal and Suboptimal Secondary Structure for RNA. H.M. Martinez, Detecting Pseudoknots and Other Local Base-Pairing Structures in RNA Sequences. D. Gautheret, F. Major, and R. Cedergren, Computer Modeling and Display of RNA Secondary and Tertiary Structures. Aligning Protein and Nucleic Acid Sequences: D.G. George, W.C. Barker, and L.T. Hunt, Mutation Data Matrix and Its Uses. P. Argos and M. Vingron, Sensitivity Comparison of Protein Amino Acid Sequences. M. Murata, Three-Way Needleman-Wunsch Algorithm. D.-F. Feng and R.F. Doolittle, Progressive Alignment and Phylogenetic Tree Construction of Protein Sequences. S. Karlin, B.E. Blaisdell, and V. Brendel, Identification of Significant Sequence Patterns in Proteins. G.J. Barton, Protein Multiple Sequence Alignment and Flexible Pattern Matching. D. Sankoff, R. Cedergren, and Y. Abel, Genomic Divergence through Gene Rearrangement. D.J. Bacon and W.F. Anderson, Multiple Sequence Comparison. M. Vihinen, Simultaneous Comparison of Several Sequences. W.R. Taylor, Hierarchical Method to Align Large Numbers of Biological Sequences. J.F. Collins and A.F.W. Coulson, Significance of Protein Sequence Similarities. G.M. Landau, U. Vishkin, and R. Nussinov, Fast Alignment of DNA and Protein Sequences. Estimating Sequence Divergence: M. Eigen and R. Winkler-Oswatitsch, Statistical Geometry on Sequence Space. T. Gojobori, E.N. Moriyama, and M. Kimura, Statistical Methods for Estimating Sequence Divergence. H. Kishino and M. Hasegawa, Converting Distance to Time: Application to Human Evolution. C. Saccone, C. Lanave, G. Pesole, and G. Preparata, Influence of Base Composition on Quantitative Estimates of Gene Evolution. N. Saitou, Maximum Likelihood Methods. Phylogenetic Trees: J. Czelusniak, M. Goodman, N.D. Moncrief, and S.M. Kehoe, Maximum Parsimony Approach to Construction of Evolutionary Trees from Aligned Homologous Sequences. P.L. Williams and W.M. Fitch, Phylogeny Determination Using Dynamically Weighted Parsimony Method. J. Hein, Unified Approach to Alignment and Phylogenies. W.-H. Li and M. Gouy, Statistical Tests of Molecular Phylogenies. R.F. Doolittle and D.-F. Feng, Nearest Neighbor Procedure for Relating Progressively Aligned Amino Acid Sequences. M.S. Johnson, A. ~ajSali, and T.L. Blundell, Phylogenetic Relationships from Three-Dimensional Protein Structures. Each chapter includes references. Author Index. Subject Index. <s> BIB001 </s> The gene identification problem: An overview for developers <s> INTRODUCTION <s> GCG: Fragment Assembly Programs. GCG: Drawing Linear Restriction Maps. GCG: Drawing Circular Restriction Maps. GCG: Displaying Restriction Sites and Possible Translations in a DNA Sequence. GCG: Assembly of Sequences into New Sequence Constructs. GCG: Comparison of Sequences. GCG: Production of Multiple-Sequence Alignment. GCG: Database Searching. GCG: Pattern Recognition. GCG: Translation of DNA Sequence. GCG: Analysis of Protein Sequences. GCG: The Analysis of RNA Secondary Structure. GCG: Preparing Sequence Data for Publication. MicroGenie: Introduction and Restriction Enzyme Analysis. MicroGenie: Shotgun DNA Sequencing. MicroGenie: Translation. MicroGenie: Protein Analysis. MicroGenie: Homology Searches. PC/GENE: Sequence Entry and Assembly. PC/GENE: Restriction Enzyme Analysis. PC/GENE: Translation and Searches for Protein Coding Regions. PC/GENE: Sequence Comparisons and Homologies. PC/GENE: Database Searches. PC/GENE: Searches for Functional Sites in Nucleic Acids and Proteins. Using the FASTA Program to Search Protein and DNA Sequence Databases. Converting Between Sequence Formats. Obtaining Software via INTERNET. Submission of Nucleotide Sequence Data to EMBL/GenBank/DDBJ. Index. <s> BIB002
In a rapidly moving field it is often easy to trace individual threads of work, but difficult to gain an overview. The first purpose of this review is to provide a concise directory to both standard and newer techniques, and so allow new developers to more quickly come to the point where they can make their own original contributions. The second purpose is to give some perspective on the structure of the field and current research directions. This includes summarizing the high points of progress to date in each of several areas, evaluating what seem to be the most productive current lines of inquiry, and attempting to predict where the most useful developments will come from in the future. While large parts of this perspective are shared by many practitioners in the field, the overall analysis necessarily represents the personal views of the author. A number of related reviews exist. A few of the more recent works on sequence analysis in general are Adams et al. (1994) , BIB001 , Gelfand (1995) ,  ,  , BIB002 ,  and  . On-line bibliographies of publications relevant to analysis of nucleotide sequences are maintained by A. Bairoch (SEQANALREF; URL http://expasy.hcuge.ch on the World-Wide Web) and M. Gelfand (FANS-REF; ftp to imb.imb.ac.ru; in directory BIBLIO).  and  give overviews of the gene identification problem. Fickett & Tung (1992) review recognizable statistical regularities in protein coding regions. Doolittle (1986) and Gish & States (1993) discuss the interpretation of similarity schemes in the context of gene identification. The present review is primarily a guide to current techniques relevant to future development, rather than being a guide to current tools. The review is mostly restricted to published work, though unpublished developments may be mentioned briefly. In most sections, coverage is limited to techniques that are either widely used, or which seem to us to be particularly important for future developments. Although the number of papers cited is already large, there are doubtless many others that should have been included. Experimental approaches to gene identification are assuming an increasing importance. These will not be covered here, but the computational developer must stay abreast of the rapid developments in experimental techniques as well. For a recent overview see Church et al. (1994) . The paper begins with a definition of the problem. The main body of the paper consists of an overview of computational tools and techniques broken into six (somewhat arbitrary) categories: l Sequence similarity search 0 Statistical regularities in exons l Signals: introduction l Signals: basal gene biochemistry 0 Signals: regulation of gene expression l Gene syntax and integration of information. In each of these categories the state of the field is summarized. In the last two sections, some higher level issues are considered.