Ab Initio Gene Finding & Structural Annotation
Generalized Hidden Markov Models (GHMMs)
Interactive exploration of explicit biological duration distributions f(d), semi-Markov Viterbi dynamic programming, exon-intron state machines (GENSCAN / AUGUSTUS), and splice signal decoding.
Unlike standard HMMs that emit single bases, GHMMs (Semi-Markov HMMs) emit entire biological segments of length d.
The joint probability combines:
- Duration score:
log f_q(d)from biological length models - Signal score: Splice junctions (
GT / AG), start (ATG), stop codons - Coding score: 3-periodic in-frame Markov codon potential
Geometric Memoryless Flaw
Standard HMMs enforce geometric state lengths P(d) = pd-1(1-p), which unrealistically favors 1-bp exons. GHMMs allow explicit density curves f(d) peaked at true biological lengths (100–200 bp).
Eukaryotic Splicing Signals
Spliceosomes recognize canonical consensus dinucleotides: GT at the 5' donor site and AG at the 3' acceptor site preceded by a polypyrimidine tract.
Ab Initio Gene Finders
Canonical tools like GENSCAN, AUGUSTUS, and SNAP utilize GHMMs with isochore-specific GC models and phylogenetic conservation to predict protein-coding structures directly from raw DNA.