Analysis and Predictions from Escherichia coli Sequences , or E . coli In Silico

Bacteria have been studied as living entities (in vivo) for 150 years and in cell-free systems (in vitro) for almost half that time. With the availability of DNA sequence information, it has become evident that genes can also be studied as lines of text. A new domain of knowledge and research concerned with this means of studying living systems has arisen; it has been referred to as informatics but also involves standard aspects of mathematics and statistics as well. Beside using computer programs that mechanically perform standard but tedious analysis of the information content of DNA, investigators are now using programs that help generate new knowledge about this information. Thus, in addition to the study of bacteria in vivo and in vitro, there is now an active endeavor studying them “in silico.” Escherichia coli has been a paradigm for such studies. It is anticipated that the E. coli genome sequence will be known by the end of 1997. In parallel, a vast amount of data on a variety of organisms has been collected, and it has become an important task not only to handle this huge quantity of information but also to extract from it the features that pertain to the concrete expression of life in general and to E. coli in particular. For the E. coli geneticist, no literature reviewing this new aspect of research exists; information is scattered through a vast number of journals and papers, often presenting independent but redundant approaches. Here we have summarized the less self-evident aspects of the data presented in the literature. Readers interested in features relevant specifically to informatics can find in the databank SEQANALREF an updated bibliography on software dealing with sequence analysis (SEQANALREF, present in the EMBL data library package, contained 3,076 references in release 64 [October 1995]). Major DNA and protein data banks are accessible on the Internet. The appropriate addresses can be found in references 23, 42, and 71. We shall follow the path that molecular geneticists pursue when they use formal techniques for investigating the significance of genes at the DNA level or of proteins at the polypeptide chain level: acquisition of sequences, analysis of these data, and management of DNA, RNA, and protein sequence data.