Hidden Markov Models

A first-order Hidden Markov Model is

completely defined by:
• A set of states.
• An alphabet of symbols.
• A transition probability matrix T=(tij)
• An emission probability matrix E=(e iX)
Linear Architecture
Loop Architecture
Wheel Architecture
 Basic Ideas
• As in speech recognition, use Hidden Markov Models (HMM) to
model a family of related primary sequences.
• As in speech recognition, in general use a left to right HMM: once the
system leaves a state it can never reenter it. The basic architecture
consists of a main backbone chain of main states, and two side chains
of insert and delete states.
• The parameters of the model are the transition and emission
probabilities. These parameters are adjusted during training from
examples.
• After learning, the model can be used in a variety of tasks including:
multiple alignments, detection of motifs, classification, data base
searches.
 HMM APPLICATIONS
• MULTIPLE ALIGNMENTS
• DATA BASE SEARCHES AND
DISCRIMINATION/CLASSIFICATION
• STRUCTURAL ANALYSIS AND
PATTERN DISCOVERY
 Multiple Alignments
• No precise definition of what a good alignment is (low
entropy, detection of motifs).
• The multiple alignment problem is NP complete (finding
longest subsequence).
• Pairwise alignment can be solved efficiently by dynamic
programming in O(N2) steps.
• For K sequences of average length N, dynamic
programming scales like O(NK), exponentially in the
number of sequences.
• Problem of variable scores and gap penalties.
 HMMs of Protein Families
• Globins
• Immunoglobulins
• Kinases
• G-Protein-Coupled Receptors
• Pfam is a data base of protein domains
 HMMs of DNA
• coding/non-coding regions (E. Coli)
• exons/introns/acceptor sites
• promoter regions
• gene finding
 IMMUNOGLOBULINS
• 294 sequences (V regions) with minimum
length 90, average length 117, and maximal
length 254
• linear model of length 117 trained with a
random subset of 150 sequences
IG MODEL ENTROPY
IG EMISSIONS
IG Viterbi Path
IG MULTIPLE ALIGNMENT
 G-PROTEIN-COUPLED
RECEPTORS
• 145 sequences with minimum length 310,
average length 430, and maximal length
764.
• Model trained with 143 sequences (3
sequences contained undefined symbols)
using Viterbi learning.
GPCR ENTROPY
GPCR HYDROPATHY
GPCR Model Structure
GPCR SCORING
PROMOTER ENTROPY
PROMOTER BENDABILITY
PROMOTER PROPELLER
TWIST
 SOFTWARE STRUCTURE
• OBJECT-ORIENTED LIBRARY FOR
MACHINE LEARNING
• ENGINE IN C++
• GRAPHICAL USER INTERFACE IN
JAVA
• RUNS UNDER WINDOWS NT AND
UNIX (SOLARIS, IRIX)
 INFORMATION
• ADDITIONAL INFORMATION,
POINTERS, REFERENCES, AND
SOFTWARE DOWNLOAD:

WWW.NETID.COM