Alignments anchored on genomic landmarks can aid in the identification of regulatory elements

• DOI: 10.1093/bioinformatics/bti1028
• Publication Date: 2005-06-16T13:08:03Z
• Authors: K. Tharakaraman; L. Marino-Ramirez; S. Sheetlin; D. Landsman; J. L. Spouge
• Keywords: 0301 basic medicine; Models, Statistical; Base Sequence; Nucleotides; Amino Acid Motifs; Molecular Sequence Data; Computational Biology; DNA; Genomics; Regulatory Sequences, Nucleic Acid; 03 medical and health sciences; Cluster Analysis; Humans; Transcription Initiation Site; Databases, Protein; Promoter Regions, Genetic; Sequence Alignment; Software

The transcription start site (TSS) has been located for an increasing number of genes across several organisms. Statistical tests have shown that some cis-acting regulatory elements positional preferences with respect to the TSS, but few strategies emerged locating by their preferences. This paper elaborates such a strategy. First, we align promoter regions without gaps, anchoring alignment on each promoter's TSS. Second, apply novel word-specific mask. Third, clustering test related gapless BLAST statistics. examines whether any specific word is placed unusually consistently Finally, our program A-GLAM, extension GLAM program, uses significant positions as new 'anchors' realign sequences. A Gibbs sampling algorithm then locates putative elements. Usually, requires preliminary masking step, avoid convergence onto dominant uninteresting signal from DNA repeat. However, since anchors focus A-GLAM motif interest, repeats during becomes unnecessary.In set human sequences experimentally characterized TSSs, placement 791 octonucleotide words was consistent (multiple corrected P < 0.05). Alignments anchored these sometimes statistically motifs inaccessible or AlignACE.The and list are available at ftp://ftp.ncbi.nih.gov/pub/spouge/papers/archive/AGLAM/.