In bioinformatics, GLIMMER (Gene Locator and Interpolated Markov ModelER) is used to find genes in prokaryotic DNA. "It is effective at finding genes in bacteria, archea, viruses, typically finding 98-99% of all relatively long protein coding genes". GLIMMER was the first system that used the interpolated Markov model to identify coding regions. The GLIMMER software is open source and is maintained by Steven Salzberg, Art Delcher, and their colleagues at the Center for Computational Biology at Johns Hopkins University. The original GLIMMER algorithms and software were designed by Art Delcher, Simon Kasif and Steven Salzberg and applied to bacterial genome annotation in collaboration with Owen White.
Versions
GLIMMER 1.0 First Version of GLIMMER "i.e., GLIMMER 1.0" was released in 1998 and it was published in the paper Microbial gene identification using interpolated Markov model. Markov models were used to identify microbial genes in GLIMMER 1.0. GLIMMER considers the local composition sequence dependencies which makes GLIMMER more flexible and more powerful when compared to fixed-order Markov model. There was a comparison made between interpolated Markov model used by GLIMMER and fifth order Markov model in the paper Microbial gene identification using interpolated Markov models. "GLIMMER algorithm found 1680 genes out of 1717 annotated genes in Haemophilus influenzae where fifth order Markov model found 1574 genes. GLIMMER found 209 additional genes which were not included in 1717 annotated genes where fifth order Markov model found 104 genes."'
GLIMMER 2.0 Second Version of GLIMMER i.e., GLIMMER 2.0 was released in 1999 and it was published in the paper Improved microbial identification with GLIMMER. This paper provides significant technical improvements such as using interpolated context model instead of interpolated Markov model and resolving overlapping genes which improves the accuracy of GLIMMER. Interpolated context models are used instead of interpolated Markov model which gives the flexibility to select any base. In interpolated Markov model probability distribution of a base is determined from the immediate preceding bases. If the immediate preceding base is irrelevant amino acid translation, interpolated Markov model still considers the preceding base to determine the probability of given base where as interpolated context model which was used in GLIMMER 2.0 can ignore irrelevant bases. False positive predictions were increased in GLIMMER 2.0 to reduce the number of false negative predictions. Overlapped genes are also resolved in GLIMMER 2.0. Various comparisons between GLIMMER 1.0 and GLIMMER 2.0 were made in the paper Improved microbial identification with GLIMMER which shows improvement in the later version. "Sensitivity of GLIMMER 1.0 ranges from 98.4 to 99.7% with an average of 99.1% where as GLIMMER 2.0 has a sensitivity range from 98.6 to 99.8% with an average of 99.3%. GLIMMER 2.0 is very effective in finding genes of high density. The parasite Trypanosoma brucei, responsible for causing African sleeping sickness is being identified by GLIMMER 2.0"
GLIMMER 3.0 Third version of GLIMMER, "GLIMMER 3.0" was released in 2007 and it was published in the paper Identifying bacterial genes and endosymbiont DNA with Glimmer. This paper describes several major changes made to the GLIMMER system including improved methods to identify coding regions and start codon. Scoring of ORF in GLIMMER 3.0 is done in reverse order i.e., starting from stop codon and moves back towards the start codon. Reverse scanning helps in identifying the coding portion of the gene more accurately which is contained in the context window of IMM. GLIMMER 3.0 also improves the generated training set data by comparing the long-ORF with universal amino acid distribution of widely disparate bacterial genomes."GLIMMER 3.0 has an average long-ORF output of 57% for various organisms where as GLIMMER 2.0 has an average long-ORF output of 39%." GLIMMER 3.0 reduces the rate of false positive predictions which were increased in GLIMMER 2.0 to reduce the number of false negative predictions. "GLIMMER 3.0 has a start-site prediction accuracy of 99.5% for 3'5' matches where as GLIMMER 2.0 has 99.1% for 3'5' matches. GLIMMER 3.0 uses a new algorithm for scanning coding regions, a new start site detection module, and architecture which integrates all gene predictions across an entire genome." Minimum description length
Theoretical and Biological Foundation The GLIMMER project helped introduce and popularize the use of variable length models in Computational Biology and Bioinformatics that subsequently have been applied to numerous problems such as protein classification and others. Variable length modeling was originally pioneered by information theorists and subsequently ingeniously applied and popularized in data compression (e.g. Ziv-Lempel compression). Prediction and compression are intimately linked using Minimum Description Length Principles. The basic idea is to create a dictionary of frequent words (motifs in biological sequences). The intuition is that the frequently occurring motifs are likely to be most predictive and informative. In GLIMMER the interpolated model is a mixture model of the probabilities of these relatively common motifs. Similarly to the development of HMMs in Computational Biology, the authors of GLIMMER were conceptually influenced by the previous application of another variant of interpolated Markov models to speech recognition by researchers such as Fred Jelinek (IBM) and Eric Ristad (Princeton). The learning algorithm in GLIMMER is different from these earlier approaches.
Access GLIMMER can be downloaded from The Glimmer home page (requires a C++ compiler). Alternatively, an online version is hosted by NCBI [link removed].
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