PipMaker

PipMaker compares long genomic DNA sequences to identify conserved segments and produce percent identity plots and high-resolution alignments that support comparative genomics and regulatory element discovery.

Key Features:

• Percent Identity Plot (PIP): PipMaker generates percent identity plots that represent the alignment position and degree of similarity between two DNA sequences and can annotate the horizontal axis with exons and repetitive elements using color coding.
• Dot Plot Visualization: PipMaker produces dot plots that display the locations of aligned segments between sequences to reveal conserved regions.
• Support for Unfinished Sequences: The system accepts one sequence as unoriented and unordered contigs to accommodate unfinished or "working draft" genomic sequences.
• MultiPipMaker Capabilities: MultiPipMaker aligns multiple long genomic DNA sequences against a contiguous reference and produces stacked percent identity plots (MultiPips) alongside nucleotide-level multiple alignments.
• Pattern and Matrix Search Tools: MultiPipMaker searches for conserved matches to user-specified sequence patterns and position weight matrices that describe transcription factor binding sites.

Scientific Applications:

• Comparative Genomics: PipMaker is used to compare genomic sequences from related species to infer protein-coding regions and cis-regulatory elements based on sequence conservation and divergence rates.
• Regulatory Element Identification: Analysis of conserved noncoding sequences with MultiPipMaker identifies candidate gene regulatory regions, exemplified by candidate regulatory regions in WNT2 that were followed by transfection assay validation.
• Phylogenetic Analysis: Alignments produced by MultiPipMaker can be used to assess evolutionary relationships, for example supporting that horses are more closely related to cats than to cows.

Methodology:

PipMaker and MultiPipMaker use alignment algorithms to compute sequence similarities and nucleotide-level multiple alignments, generate percent identity plots and dot plots, and perform searches for conserved matches to user-specified patterns and position weight matrices.