Pairagon

Pairagon aligns spliced complementary DNA (cDNA) sequences to genomic DNA using a pair hidden Markov model (pair-HMM) to identify exon–intron structure for genome annotation.

Key Features:

• Pair-HMM Based Alignment: Employs a pair hidden Markov model (pair-HMM) to perform spliced cDNA-to-genome alignments and identify exon–intron boundaries.
• High Accuracy Across Sequence Identities: Demonstrates over 99.6% accuracy for sequences with 100% identity and approximately 87% accuracy for human/mouse alignments at 85% sequence identity.
• Error Minimization: Produces alignment error rates one quarter of those observed with other aligners on perfect simulated cDNA sequences.
• Efficiency and Speed Considerations: Balances enhanced scoring systems with runtime and memory requirements using strategic heuristics to maintain computational efficiency.
• Cross-Species Alignment Robustness: Handles varying sequence identities enabling cross-species alignments such as human, mouse, and rat orthologous transcripts.

Scientific Applications:

• Genomic Annotation: Identifying exon–intron structures and annotating gene models by aligning spliced cDNAs to genomes.
• Cross-Species Comparative Genomics: Aligning orthologous transcripts across species (human, mouse, rat) for evolutionary and functional genomics studies.

Methodology:

Generates "perfect" simulated cDNA by splicing exon sequences from reference genomes (fly and human), aligns them to mutated versions of the complete genome using Pairagon and other aligners for evaluation, and assesses performance on natural cross-species sequence alignments.