CAP 5510: Introduction to Bioinformatics CGS 5166: Bioinformatics Tools. Giri Narasimhan
|
|
|
- Lambert Brown
- 5 years ago
- Views:
Transcription
1 CAP 5510: Introduction to Bioinformatics CGS 5166: Bioinformatics Tools Giri Narasimhan ECS 254; Phone: x3748
2 Describing & Modeling Patterns
3 Patterns in DNA Sequences q Signals in DNA sequence control events Start and end of genes Start and end of introns Transcription factor binding sites (regulatory elements) Ribosome binding sites q Detection of these patterns are useful for Understanding gene structure Understanding gene regulation 2/9/15 CAP5510 / CGS
4 Motifs in DNA Sequences q Given a collection of DNA sequences of promoter regions, describe the transcription factor binding sites (also called regulatory elements) Example: 2/9/15 CAP5510 / CGS
5 Motifs in DNA Sequences 2/9/15 CAP5510 / CGS
6 More Motifs in E. Coli DNA Sequences 2/9/15 CAP5510 / CGS
7 2/9/15 CAP5510 / CGS
8 Other Motifs in DNA Sequences: Human Splice Junctions 2/9/15 CAP5510 / CGS
9 Motifs 2/9/15 CAP5510 / CGS
10 Pattern: Representations GAGGTAAAC TCCGTAAGT CAGGTTGGA ACAGTCAGT TAGGTCATT TAGGTACTG ATGGTAACT CAGGTATAC TGTGTGAGT AAGGTAAGT Alignments Consensus Sequences Logo Formats... TAGGTAAGT TAGGTAAGT 2/9/15 CAP5510 / CGS
11 Profiles GAGGTAAAC TCCGTAAGT CAGGTTGGA ACAGTCAGT TAGGTCATT TAGGTACTG ATGGTAACT CAGGTATAC TGTGTGAGT AAGGTAAGT A C G T A C G T Frequency Matrix Relative Frequencies 2/9/15 CAP5510 / CGS
12 Profiles GAGGTAAAC TCCGTAAGT CAGGTTGGA ACAGTCAGT TAGGTCATT TAGGTACTG ATGGTAACT CAGGTATAC TGTGTGAGT AAGGTAAGT A C G T Relative Frequencies A C G T /9/15 CAP5510 / CGS
13 Profile entries: P ij = ln (f ij /b i ) Zero counts: f ij = (c ij +αb i )/ (n+α) Profiles A C G T Relative Frequencies A C G T /9/15 CAP5510 / CGS
14 CpG Islands q Regions in DNA sequences with increased occurrences of substring CG q Rare: typically C gets methylated and then mutated into a T. q Often around promoter or start regions of genes q Few hundred to a few thousand bases long 2/9/15 CAP5510 / CGS
15 Problem 1: Input: Small sequence S Output: Is S from a CpG island? Build Markov models: M+ and M Then compare 2/9/15 CAP5510 / CGS
16 Markov Models + A C G T A C G T A A C C G G T T /9/15 CAP5510 / CGS
17 How to distinguish? q Compute S ( P( x M + ) % & # ' P( x M ) $ L ( i 1) i ( x) = log = log = rx( i 1) i= 1 ( p & ' m x x ( i 1) x x i % # $ L i= 1 x i r=p/m A C G T A C G T Score(GCAC) = < 0. GCAC not from CpG island. Score(GCTC) = > 0. GCTC from CpG island. 2/9/15 CAP5510 / CGS
18 Problem 1: Input: Small sequence S Output: Is S from a CpG island? Build Markov Models: M+ & M- Then compare Problem 2: Input: Long sequence S Output: Identify the CpG islands in S. Markov models are inadequate. Need Hidden Markov Models. 2/9/15 CAP5510 / CGS
19 Markov Models + A C G T A P(A+ A+) A+ T+ C G T C+ P(G+ C+) G+ 2/9/15 CAP5510 / CGS
20 CpG Island + in an ocean of First order Hidden Markov Model P(A+ A+) A+ MM=16, HMM= 64 transition probabilities (adjacent bp) T+ A- T- C+ P(G+ C+) G+ C- G- 2/9/15 CAP5510 / CGS
21 Hidden Markov Model (HMM) States Transitions Transition Probabilities Emissions Emission Probabilities What is hidden about HMMs? Answer: The path through the model is hidden since there are many valid paths. 2/9/15 CAP5510 / CGS
22 How to Solve Problem 2? q Solve the following problem: Input: Hidden Markov Model M, parameters Θ, emitted sequence S Output: Most Probable Path Π How: Viterbi s Algorithm (Dynamic Programming) Define Π[i,j] = MPP for first j characters of S ending in state i Define P[i,j] = Probability of Π[i,j] Compute state i with largest P[i,j]. 2/9/15 CAP5510 / CGS
23 Profile entries: P ij = ln (f ij /b i ) Zero counts: f ij = (c ij +αb i )/ (n+α) Profiles A C G T Relative Frequencies A C G T Profiles; Position Weight Matrix (PWM); Position-Specific Scoring Matrix (PSSM) 2/9/15 CAP5510 / CGS
24 Profile HMMs START STATE 1 STATE 2 STATE 3 STATE 4 STATE 5 STATE 6 END 2/9/15 CAP5510 / CGS
25 Profile HMMs with InDels Insertions Deletions Insertions & Deletions DELETE 1 DELETE 2 DELETE 3 START STATE 1 STATE 2 STATE 3 STATE 4 STATE 5 STATE 6 END INSERT 3 INSERT 4 2/9/15 CAP5510 / CGS
26 Profile HMMs with InDels DELETE 1 DELETE 2 DELETE 3 DELETE 4 DELETE 5 DELETE 6 START STATE 1 STATE 2 STATE 3 STATE 4 STATE 5 STATE 6 END INSERT 4 INSERT 4 INSERT 3 INSERT 4 INSERT 4 INSERT 4 Missing transitions from DELETE j to INSERT j and from INSERT j to DELETE j+1. 2/9/15 CAP5510 / CGS
27 HMM for Sequence Alignment 2/9/15 CAP5510 / CGS
28 Profile HMM Software q HMMER q SAM q PFTOOLS q HMMpro q GENEWISE q PROBE ftp://ftp.ncbi.nih.gov/pub/neuwald/probe1.0/ q META-MEME q BLOCKS q PSI-BLAST q Read more about Profile HMMs at 2/9/15 CAP5510 / CGS
29 How to model Pairwise Sequence Alignment LEAPVE LAPVIE DELETE Pair HMMs Emit pairs of synbols Emission probs? Related to Sub. Matrices START MATCH END INSERT How to deal with InDels? Global Alignment? Local? Related to Sub. Matrices 2/9/15 CAP5510 / CGS
30 How to model Pairwise Local Alignments? START Skip Module Align Module Skip Module END How to model Pairwise Local Alignments with gaps? START Skip Module Align Module Skip Module END 2/9/15 CAP5510 / CGS
31 Standard HMM architectures 2/9/15 CAP5510 / CGS
32 Standard HMM architectures 2/9/15 CAP5510 / CGS
33 Standard HMM architectures 2/9/15 CAP5510 / CGS
34 Problem 3: LIKELIHOOD QUESTION Input: Sequence S, model M, state i Output: Compute the probability of reaching state i with sequence S using model M Backward Algorithm (DP) Problem 4: LIKELIHOOD QUESTION Input: Sequence S, model M Output: Compute the probability that S was emitted by model M Forward Algorithm (DP) 2/9/15 CAP5510 / CGS
35 Problem 5: LEARNING QUESTION Input: model structure M, Training Sequence S Output: Compute the parameters Θ Criteria: ML criterion maximize P(S M, Θ) HOW??? Problem 6: DESIGN QUESTION Input: Training Sequence S Output: Choose model structure M, and compute the parameters Θ No reasonable solution Standard models to pick from 2/9/15 CAP5510 / CGS
36 Iterative Solution to the LEARNING QUESTION (Problem 5) q Pick initial values for parameters Θ 0 q Repeat Run training set S on model M Count # of times transition i j is made Count # of times letter x is emitted from state i Update parameters Θ q Until (some stopping condition) 2/9/15 CAP5510 / CGS
37 Entropy q Entropy measures the variability observed in given data. E = c log pc pc q Entropy is useful in multiple alignments & profiles. q Entropy is max when uncertainty is max. 2/9/15 CAP5510 / CGS
38 G-Protein Couple Receptors q Transmembrane proteins with 7 α-helices and 6 loops; many subfamilies q Highly variable: aa in length, some have only 20% identity. q [Baldi & Chauvin, 94] HMM for GPCRs q HMM constructed with 430 match states (avg length of sequences) ; Training: with 142 sequences, 12 iterations 2/9/15 CAP5510 / CGS
39 GPCR - Analysis q Compute main state entropy values H i = a q For every sequence from test set (142) & random set (1600) & all SWISS-PROT proteins e Compute the negative log of probability of the most probable path π ia log e ia ( P( π S, )) Score( S) = log M 2/9/15 CAP5510 / CGS
40 GPCR Analysis 2/9/15 CAP5510 / CGS
41 Entropy 2/9/15 CAP5510 / CGS
42 GPCR Analysis (Cont d) 2/9/15 CAP5510 / CGS
43 Applications of HMM for GPCR q Bacteriorhodopsin Transmembrane protein with 7 domains But it is not a GPCR Compute score and discover that it is close to the regression line. Hence not a GPCR. q Thyrotropin receptor precursors All have long initial loop on INSERT STATE 20. Also clustering possible based on distance to regression line. 2/9/15 CAP5510 / CGS
44 HMMs Advantages q Sound statistical foundations q Efficient learning algorithms q Consistent treatment for insert/delete penalties for alignments in the form of locally learnable probabilities q Capable of handling inputs of variable length q Can be built in a modular & hierarchical fashion; can be combined into libraries. q Wide variety of applications: Multiple Alignment, Data mining & classification, Structural Analysis, Pattern discovery, Gene prediction. 2/9/15 CAP5510 / CGS
45 HMMs Disadvantages q Large # of parameters. q Cannot express dependencies & correlations between hidden states. 2/9/15 CAP5510 / CGS
46 References q Krogh, Brown, Mian, Sjolander, Haussler, J. Mol. Biol. 235: , 1994 q Gribskov, Luthy, Eisenberg, Meth. Enzymol. 183: , 1995 q Gribskov, McLachlan, Eisenberg, Proc Natl. Acad. Sci. 84: , /9/15 CAP5510 / CGS
Giri Narasimhan. CAP 5510: Introduction to Bioinformatics. ECS 254; Phone: x3748
CAP 5510: Introduction to Bioinformatics Giri Narasimhan ECS 254; Phone: x3748 giri@cis.fiu.edu www.cis.fiu.edu/~giri/teach/bioinfs07.html 2/14/07 CAP5510 1 CpG Islands Regions in DNA sequences with increased
Statistical Machine Learning Methods for Bioinformatics II. Hidden Markov Model for Biological Sequences
Statistical Machine Learning Methods for Bioinformatics II. Hidden Markov Model for Biological Sequences Jianlin Cheng, PhD Department of Computer Science University of Missouri 2008 Free for Academic
An Introduction to Bioinformatics Algorithms Hidden Markov Models
Hidden Markov Models Outline 1. CG-Islands 2. The Fair Bet Casino 3. Hidden Markov Model 4. Decoding Algorithm 5. Forward-Backward Algorithm 6. Profile HMMs 7. HMM Parameter Estimation 8. Viterbi Training
Hidden Markov Models
Hidden Markov Models Outline 1. CG-Islands 2. The Fair Bet Casino 3. Hidden Markov Model 4. Decoding Algorithm 5. Forward-Backward Algorithm 6. Profile HMMs 7. HMM Parameter Estimation 8. Viterbi Training
Hidden Markov Models. Main source: Durbin et al., Biological Sequence Alignment (Cambridge, 98)
Hidden Markov Models Main source: Durbin et al., Biological Sequence Alignment (Cambridge, 98) 1 The occasionally dishonest casino A P A (1) = P A (2) = = 1/6 P A->B = P B->A = 1/10 B P B (1)=0.1... P
Statistical Machine Learning Methods for Biomedical Informatics II. Hidden Markov Model for Biological Sequences
Statistical Machine Learning Methods for Biomedical Informatics II. Hidden Markov Model for Biological Sequences Jianlin Cheng, PhD William and Nancy Thompson Missouri Distinguished Professor Department
Hidden Markov Models
Hidden Markov Models Slides revised and adapted to Bioinformática 55 Engª Biomédica/IST 2005 Ana Teresa Freitas Forward Algorithm For Markov chains we calculate the probability of a sequence, P(x) How
EECS730: Introduction to Bioinformatics
EECS730: Introduction to Bioinformatics Lecture 07: profile Hidden Markov Model http://bibiserv.techfak.uni-bielefeld.de/sadr2/databasesearch/hmmer/profilehmm.gif Slides adapted from Dr. Shaojie Zhang
Hidden Markov Models
Hidden Markov Models Outline CG-islands The Fair Bet Casino Hidden Markov Model Decoding Algorithm Forward-Backward Algorithm Profile HMMs HMM Parameter Estimation Viterbi training Baum-Welch algorithm
Page 1. References. Hidden Markov models and multiple sequence alignment. Markov chains. Probability review. Example. Markovian sequence
Page Hidden Markov models and multiple sequence alignment Russ B Altman BMI 4 CS 74 Some slides borrowed from Scott C Schmidler (BMI graduate student) References Bioinformatics Classic: Krogh et al (994)
Introduction to Hidden Markov Models for Gene Prediction ECE-S690
Introduction to Hidden Markov Models for Gene Prediction ECE-S690 Outline Markov Models The Hidden Part How can we use this for gene prediction? Learning Models Want to recognize patterns (e.g. sequence
HMMs and biological sequence analysis
HMMs and biological sequence analysis Hidden Markov Model A Markov chain is a sequence of random variables X 1, X 2, X 3,... That has the property that the value of the current state depends only on the
O 3 O 4 O 5. q 3. q 4. Transition
Hidden Markov Models Hidden Markov models (HMM) were developed in the early part of the 1970 s and at that time mostly applied in the area of computerized speech recognition. They are first described in
CISC 889 Bioinformatics (Spring 2004) Hidden Markov Models (II)
CISC 889 Bioinformatics (Spring 24) Hidden Markov Models (II) a. Likelihood: forward algorithm b. Decoding: Viterbi algorithm c. Model building: Baum-Welch algorithm Viterbi training Hidden Markov models
HMM applications. Applications of HMMs. Gene finding with HMMs. Using the gene finder
HMM applications Applications of HMMs Gene finding Pairwise alignment (pair HMMs) Characterizing protein families (profile HMMs) Predicting membrane proteins, and membrane protein topology Gene finding
Patterns and profiles applications of multiple alignments. Tore Samuelsson March 2013
Patterns and profiles applications of multiple alignments Tore Samuelsson March 3 Protein patterns and the PROSITE database Proteins that bind the nucleotides ATP or GTP share a short sequence motif Entry
Chapter 4: Hidden Markov Models
Chapter 4: Hidden Markov Models 4.1 Introduction to HMM Prof. Yechiam Yemini (YY) Computer Science Department Columbia University Overview Markov models of sequence structures Introduction to Hidden Markov
Hidden Markov Models (I)
GLOBEX Bioinformatics (Summer 2015) Hidden Markov Models (I) a. The model b. The decoding: Viterbi algorithm Hidden Markov models A Markov chain of states At each state, there are a set of possible observables
Giri Narasimhan. CAP 5510: Introduction to Bioinformatics. ECS 254; Phone: x3748
CAP 5510: Introduction to Bioinformatics Giri Narasimhan ECS 254; Phone: x3748 giri@cis.fiu.edu www.cis.fiu.edu/~giri/teach/bioinfs07.html 2/8/07 CAP5510 1 Pattern Discovery 2/8/07 CAP5510 2 Patterns Nature
Markov Models & DNA Sequence Evolution
7.91 / 7.36 / BE.490 Lecture #5 Mar. 9, 2004 Markov Models & DNA Sequence Evolution Chris Burge Review of Markov & HMM Models for DNA Markov Models for splice sites Hidden Markov Models - looking under
Stephen Scott.
1 / 27 sscott@cse.unl.edu 2 / 27 Useful for modeling/making predictions on sequential data E.g., biological sequences, text, series of sounds/spoken words Will return to graphical models that are generative
An Introduction to Sequence Similarity ( Homology ) Searching
An Introduction to Sequence Similarity ( Homology ) Searching Gary D. Stormo 1 UNIT 3.1 1 Washington University, School of Medicine, St. Louis, Missouri ABSTRACT Homologous sequences usually have the same,
Hidden Markov Models (HMMs) and Profiles
Hidden Markov Models (HMMs) and Profiles Swiss Institute of Bioinformatics (SIB) 26-30 November 2001 Markov Chain Models A Markov Chain Model is a succession of states S i (i = 0, 1,...) connected by transitions.
Hidden Markov Models. x 1 x 2 x 3 x K
Hidden Markov Models 1 1 1 1 2 2 2 2 K K K K x 1 x 2 x 3 x K Viterbi, Forward, Backward VITERBI FORWARD BACKWARD Initialization: V 0 (0) = 1 V k (0) = 0, for all k > 0 Initialization: f 0 (0) = 1 f k (0)
Computational Genomics and Molecular Biology, Fall
Computational Genomics and Molecular Biology, Fall 2014 1 HMM Lecture Notes Dannie Durand and Rose Hoberman November 6th Introduction In the last few lectures, we have focused on three problems related
Lecture 8 Learning Sequence Motif Models Using Expectation Maximization (EM) Colin Dewey February 14, 2008
Lecture 8 Learning Sequence Motif Models Using Expectation Maximization (EM) Colin Dewey February 14, 2008 1 Sequence Motifs what is a sequence motif? a sequence pattern of biological significance typically
Hidden Markov Models for biological sequence analysis
Hidden Markov Models for biological sequence analysis Master in Bioinformatics UPF 2017-2018 http://comprna.upf.edu/courses/master_agb/ Eduardo Eyras Computational Genomics Pompeu Fabra University - ICREA
Gibbs Sampling Methods for Multiple Sequence Alignment
Gibbs Sampling Methods for Multiple Sequence Alignment Scott C. Schmidler 1 Jun S. Liu 2 1 Section on Medical Informatics and 2 Department of Statistics Stanford University 11/17/99 1 Outline Statistical
Today s Lecture: HMMs
Today s Lecture: HMMs Definitions Examples Probability calculations WDAG Dynamic programming algorithms: Forward Viterbi Parameter estimation Viterbi training 1 Hidden Markov Models Probability models
Plan for today. ! Part 1: (Hidden) Markov models. ! Part 2: String matching and read mapping
Plan for today! Part 1: (Hidden) Markov models! Part 2: String matching and read mapping! 2.1 Exact algorithms! 2.2 Heuristic methods for approximate search (Hidden) Markov models Why consider probabilistics
CSCE 478/878 Lecture 9: Hidden. Markov. Models. Stephen Scott. Introduction. Outline. Markov. Chains. Hidden Markov Models. CSCE 478/878 Lecture 9:
Useful for modeling/making predictions on sequential data E.g., biological sequences, text, series of sounds/spoken words Will return to graphical models that are generative sscott@cse.unl.edu 1 / 27 2
Hidden Markov Models. Three classic HMM problems
An Introduction to Bioinformatics Algorithms www.bioalgorithms.info Hidden Markov Models Slides revised and adapted to Computational Biology IST 2015/2016 Ana Teresa Freitas Three classic HMM problems
Sequence Alignment Techniques and Their Uses
Sequence Alignment Techniques and Their Uses Sarah Fiorentino Since rapid sequencing technology and whole genomes sequencing, the amount of sequence information has grown exponentially. With all of this
Hidden Markov Models for biological sequence analysis I
Hidden Markov Models for biological sequence analysis I Master in Bioinformatics UPF 2014-2015 Eduardo Eyras Computational Genomics Pompeu Fabra University - ICREA Barcelona, Spain Example: CpG Islands
Bioinformatics 1--lectures 15, 16. Markov chains Hidden Markov models Profile HMMs
Bioinformatics 1--lectures 15, 16 Markov chains Hidden Markov models Profile HMMs target sequence database input to database search results are sequence family pseudocounts or background-weighted pseudocounts
Markov Chains and Hidden Markov Models. COMP 571 Luay Nakhleh, Rice University
Markov Chains and Hidden Markov Models COMP 571 Luay Nakhleh, Rice University Markov Chains and Hidden Markov Models Modeling the statistical properties of biological sequences and distinguishing regions
HIDDEN MARKOV MODELS
HIDDEN MARKOV MODELS Outline CG-islands The Fair Bet Casino Hidden Markov Model Decoding Algorithm Forward-Backward Algorithm Profile HMMs HMM Parameter Estimation Viterbi training Baum-Welch algorithm
Computational Genomics and Molecular Biology, Fall
Computational Genomics and Molecular Biology, Fall 2011 1 HMM Lecture Notes Dannie Durand and Rose Hoberman October 11th 1 Hidden Markov Models In the last few lectures, we have focussed on three problems
Pairwise sequence alignment and pair hidden Markov models
Pairwise sequence alignment and pair hidden Markov models Martin C. Frith April 13, 2012 ntroduction Pairwise alignment and pair hidden Markov models (phmms) are basic textbook fare [2]. However, there
An Introduction to Bioinformatics Algorithms Hidden Markov Models
Hidden Markov Models Hidden Markov Models Outline CG-islands The Fair Bet Casino Hidden Markov Model Decoding Algorithm Forward-Backward Algorithm Profile HMMs HMM Parameter Estimation Viterbi training
Week 10: Homology Modelling (II) - HHpred
Week 10: Homology Modelling (II) - HHpred Course: Tools for Structural Biology Fabian Glaser BKU - Technion 1 2 Identify and align related structures by sequence methods is not an easy task All comparative
CSCE 471/871 Lecture 3: Markov Chains and
and and 1 / 26 sscott@cse.unl.edu 2 / 26 Outline and chains models (s) Formal definition Finding most probable state path (Viterbi algorithm) Forward and backward algorithms State sequence known State
Hidden Markov Models (HMMs) November 14, 2017
Hidden Markov Models (HMMs) November 14, 2017 inferring a hidden truth 1) You hear a static-filled radio transmission. how can you determine what did the sender intended to say? 2) You know that genes
Motifs and Logos. Six Introduction to Bioinformatics. Importance and Abundance of Motifs. Getting the CDS. From DNA to Protein 6.1.
Motifs and Logos Six Discovering Genomics, Proteomics, and Bioinformatics by A. Malcolm Campbell and Laurie J. Heyer Chapter 2 Genome Sequence Acquisition and Analysis Sami Khuri Department of Computer
BMI/CS 576 Fall 2016 Final Exam
BMI/CS 576 all 2016 inal Exam Prof. Colin Dewey Saturday, December 17th, 2016 10:05am-12:05pm Name: KEY Write your answers on these pages and show your work. You may use the back sides of pages as necessary.
Hidden Markov Models. x 1 x 2 x 3 x K
Hidden Markov Models 1 1 1 1 2 2 2 2 K K K K x 1 x 2 x 3 x K HiSeq X & NextSeq Viterbi, Forward, Backward VITERBI FORWARD BACKWARD Initialization: V 0 (0) = 1 V k (0) = 0, for all k > 0 Initialization:
Example: The Dishonest Casino. Hidden Markov Models. Question # 1 Evaluation. The dishonest casino model. Question # 3 Learning. Question # 2 Decoding
Example: The Dishonest Casino Hidden Markov Models Durbin and Eddy, chapter 3 Game:. You bet $. You roll 3. Casino player rolls 4. Highest number wins $ The casino has two dice: Fair die P() = P() = P(3)
Lecture 7 Sequence analysis. Hidden Markov Models
Lecture 7 Sequence analysis. Hidden Markov Models Nicolas Lartillot may 2012 Nicolas Lartillot (Universite de Montréal) BIN6009 may 2012 1 / 60 1 Motivation 2 Examples of Hidden Markov models 3 Hidden
Hidden Markov Models
Hidden Markov Models Slides revised and adapted to Bioinformática 55 Engª Biomédica/IST 2005 Ana Teresa Freitas CG-Islands Given 4 nucleotides: probability of occurrence is ~ 1/4. Thus, probability of
Protein Bioinformatics. Rickard Sandberg Dept. of Cell and Molecular Biology Karolinska Institutet sandberg.cmb.ki.
Protein Bioinformatics Rickard Sandberg Dept. of Cell and Molecular Biology Karolinska Institutet rickard.sandberg@ki.se sandberg.cmb.ki.se Outline Protein features motifs patterns profiles signals 2 Protein
Hidden Markov Models
Andrea Passerini passerini@disi.unitn.it Statistical relational learning The aim Modeling temporal sequences Model signals which vary over time (e.g. speech) Two alternatives: deterministic models directly
Stephen Scott.
1 / 21 sscott@cse.unl.edu 2 / 21 Introduction Designed to model (profile) a multiple alignment of a protein family (e.g., Fig. 5.1) Gives a probabilistic model of the proteins in the family Useful for
Hidden Markov Models. based on chapters from the book Durbin, Eddy, Krogh and Mitchison Biological Sequence Analysis via Shamir s lecture notes
Hidden Markov Models based on chapters from the book Durbin, Eddy, Krogh and Mitchison Biological Sequence Analysis via Shamir s lecture notes music recognition deal with variations in - actual sound -
Quantitative Bioinformatics
Chapter 9 Class Notes Signals in DNA 9.1. The Biological Problem: since proteins cannot read, how do they recognize nucleotides such as A, C, G, T? Although only approximate, proteins actually recognize
Hidden Markov Models. music recognition. deal with variations in - pitch - timing - timbre 2
Hidden Markov Models based on chapters from the book Durbin, Eddy, Krogh and Mitchison Biological Sequence Analysis Shamir s lecture notes and Rabiner s tutorial on HMM 1 music recognition deal with variations
Graph Alignment and Biological Networks
Graph Alignment and Biological Networks Johannes Berg http://www.uni-koeln.de/ berg Institute for Theoretical Physics University of Cologne Germany p.1/12 Networks in molecular biology New large-scale
Learning Sequence Motif Models Using Expectation Maximization (EM) and Gibbs Sampling
Learning Sequence Motif Models Using Expectation Maximization (EM) and Gibbs Sampling BMI/CS 776 www.biostat.wisc.edu/bmi776/ Spring 009 Mark Craven craven@biostat.wisc.edu Sequence Motifs what is a sequence
HMM : Viterbi algorithm - a toy example
MM : Viterbi algorithm - a toy example 0.6 et's consider the following simple MM. This model is composed of 2 states, (high GC content) and (low GC content). We can for example consider that state characterizes
CSEP 590A Summer Lecture 4 MLE, EM, RE, Expression
CSEP 590A Summer 2006 Lecture 4 MLE, EM, RE, Expression 1 FYI, re HW #2: Hemoglobin History Alberts et al., 3rd ed.,pg389 2 Tonight MLE: Maximum Likelihood Estimators EM: the Expectation Maximization Algorithm
CSEP 590A Summer Tonight MLE. FYI, re HW #2: Hemoglobin History. Lecture 4 MLE, EM, RE, Expression. Maximum Likelihood Estimators
CSEP 59A Summer 26 Lecture 4 MLE, EM, RE, Expression FYI, re HW #2: Hemoglobin History 1 Alberts et al., 3rd ed.,pg389 2 Tonight MLE: Maximum Likelihood Estimators EM: the Expectation Maximization Algorithm
De novo identification of motifs in one species. Modified from Serafim Batzoglou s lecture notes
De novo identification of motifs in one species Modified from Serafim Batzoglou s lecture notes Finding Regulatory Motifs... Given a collection of genes that may be regulated by the same transcription
Markov Chains and Hidden Markov Models. = stochastic, generative models
Markov Chains and Hidden Markov Models = stochastic, generative models (Drawing heavily from Durbin et al., Biological Sequence Analysis) BCH339N Systems Biology / Bioinformatics Spring 2016 Edward Marcotte,
Multiple Sequence Alignment using Profile HMM
Multiple Sequence Alignment using Profile HMM. based on Chapter 5 and Section 6.5 from Biological Sequence Analysis by R. Durbin et al., 1998 Acknowledgements: M.Sc. students Beatrice Miron, Oana Răţoi,
Data Mining in Bioinformatics HMM
Data Mining in Bioinformatics HMM Microarray Problem: Major Objective n Major Objective: Discover a comprehensive theory of life s organization at the molecular level 2 1 Data Mining in Bioinformatics
6.047/6.878/HST.507 Computational Biology: Genomes, Networks, Evolution. Lecture 05. Hidden Markov Models Part II
6.047/6.878/HST.507 Computational Biology: Genomes, Networks, Evolution Lecture 05 Hidden Markov Models Part II 1 2 Module 1: Aligning and modeling genomes Module 1: Computational foundations Dynamic programming:
Sequence Analysis, '18 -- lecture 9. Families and superfamilies. Sequence weights. Profiles. Logos. Building a representative model for a gene.
Sequence Analysis, '18 -- lecture 9 Families and superfamilies. Sequence weights. Profiles. Logos. Building a representative model for a gene. How can I represent thousands of homolog sequences in a compact
Alignment Algorithms. Alignment Algorithms
Midterm Results Big improvement over scores from the previous two years. Since this class grade is based on the previous years curve, that means this class will get higher grades than the previous years.
Amino Acid Structures from Klug & Cummings. Bioinformatics (Lec 12)
Amino Acid Structures from Klug & Cummings 2/17/05 1 Amino Acid Structures from Klug & Cummings 2/17/05 2 Amino Acid Structures from Klug & Cummings 2/17/05 3 Amino Acid Structures from Klug & Cummings
Lecture 4: Hidden Markov Models: An Introduction to Dynamic Decision Making. November 11, 2010
Hidden Lecture 4: Hidden : An Introduction to Dynamic Decision Making November 11, 2010 Special Meeting 1/26 Markov Model Hidden When a dynamical system is probabilistic it may be determined by the transition
Hidden Markov Models. Ivan Gesteira Costa Filho IZKF Research Group Bioinformatics RWTH Aachen Adapted from:
Hidden Markov Models Ivan Gesteira Costa Filho IZKF Research Group Bioinformatics RWTH Aachen Adapted from: www.ioalgorithms.info Outline CG-islands The Fair Bet Casino Hidden Markov Model Decoding Algorithm
RNA Search and! Motif Discovery" Genome 541! Intro to Computational! Molecular Biology"
RNA Search and! Motif Discovery" Genome 541! Intro to Computational! Molecular Biology" Day 1" Many biologically interesting roles for RNA" RNA secondary structure prediction" 3 4 Approaches to Structure
Pairwise alignment using HMMs
Pairwise alignment using HMMs The states of an HMM fulfill the Markov property: probability of transition depends only on the last state. CpG islands and casino example: HMMs emit sequence of symbols (nucleotides
1/22/13. Example: CpG Island. Question 2: Finding CpG Islands
I529: Machine Learning in Bioinformatics (Spring 203 Hidden Markov Models Yuzhen Ye School of Informatics and Computing Indiana Univerty, Bloomington Spring 203 Outline Review of Markov chain & CpG island
Hidden Markov Models and some applications
Oleg Makhnin New Mexico Tech Dept. of Mathematics November 11, 2011 HMM description Application to genetic analysis Applications to weather and climate modeling Discussion HMM description Application to
Giri Narasimhan. CAP 5510: Introduction to Bioinformatics. ECS 254; Phone: x3748
CAP 5510: Introduction to Bioinformatics Giri Narasimhan ECS 254; Phone: x3748 giri@cis.fiu.edu www.cis.fiu.edu/~giri/teach/bioinfs07.html 2/15/07 CAP5510 1 EM Algorithm Goal: Find θ, Z that maximize Pr
Sequence and Structure Alignment Z. Luthey-Schulten, UIUC Pittsburgh, 2006 VMD 1.8.5
Sequence and Structure Alignment Z. Luthey-Schulten, UIUC Pittsburgh, 2006 VMD 1.8.5 Why Look at More Than One Sequence? 1. Multiple Sequence Alignment shows patterns of conservation 2. What and how many
Matrix-based pattern discovery algorithms
Regulatory Sequence Analysis Matrix-based pattern discovery algorithms Jacques.van.Helden@ulb.ac.be Université Libre de Bruxelles, Belgique Laboratoire de Bioinformatique des Génomes et des Réseaux (BiGRe)
Hidden Markov Models
Hidden Markov Models A selection of slides taken from the following: Chris Bystroff Protein Folding Initiation Site Motifs Iosif Vaisman Bioinformatics and Gene Discovery Colin Cherry Hidden Markov Models
Pair Hidden Markov Models
Pair Hidden Markov Models Scribe: Rishi Bedi Lecturer: Serafim Batzoglou January 29, 2015 1 Recap of HMMs alphabet: Σ = {b 1,...b M } set of states: Q = {1,..., K} transition probabilities: A = [a ij ]
Sequence Analysis. BBSI 2006: Lecture #(χ+1) Takis Benos (2006) BBSI MAY P. Benos
Sequence Analysis BBSI 2006: Lecture #(χ+1) Takis Benos (2006) Molecular Genetics 101 What is a gene? We cannot define it (but we know it when we see it ) A loose definition: Gene is a DNA/RNA information
Profiles. Evolutionary related sequences (orthologs and paralogs) are often identified with local alignment programs like BLAST, FASTA, SSEARCH.
Profiles Tore Samuelsson Nov 9 Background Evolutionary related sequences (orthologs and paralogs) are often identified with local alignment programs like BLAST, FASTA, SSEARCH. However, these methods are
Multiple Sequence Alignment: HMMs and Other Approaches
Multiple Sequence Alignment: HMMs and Other Approaches Background Readings: Durbin et. al. Section 3.1, Ewens and Grant, Ch4. Wing-Kin Sung, Ch 6 Beerenwinkel N, Siebourg J. Statistics, probability, and
Bioinformatics 2 - Lecture 4
Bioinformatics 2 - Lecture 4 Guido Sanguinetti School of Informatics University of Edinburgh February 14, 2011 Sequences Many data types are ordered, i.e. you can naturally say what is before and what
Detecting Distant Homologs Using Phylogenetic Tree-Based HMMs
PROTEINS: Structure, Function, and Genetics 52:446 453 (2003) Detecting Distant Homologs Using Phylogenetic Tree-Based HMMs Bin Qian 1 and Richard A. Goldstein 1,2 * 1 Biophysics Research Division, University
Theoretical distribution of PSSM scores
Regulatory Sequence Analysis Theoretical distribution of PSSM scores Jacques van Helden Jacques.van-Helden@univ-amu.fr Aix-Marseille Université, France Technological Advances for Genomics and Clinics (TAGC,
STRUCTURAL BIOINFORMATICS I. Fall 2015
STRUCTURAL BIOINFORMATICS I Fall 2015 Info Course Number - Classification: Biology 5411 Class Schedule: Monday 5:30-7:50 PM, SERC Room 456 (4 th floor) Instructors: Vincenzo Carnevale - SERC, Room 704C;
6.047 / Computational Biology: Genomes, Networks, Evolution Fall 2008
MIT OpenCourseWare http://ocw.mit.edu 6.047 / 6.878 Computational Biology: Genomes, Networks, Evolution Fall 2008 For information about citing these materials or our Terms of Use, visit: http://ocw.mit.edu/terms.
Bioinformatics (GLOBEX, Summer 2015) Pairwise sequence alignment
Bioinformatics (GLOBEX, Summer 2015) Pairwise sequence alignment Substitution score matrices, PAM, BLOSUM Needleman-Wunsch algorithm (Global) Smith-Waterman algorithm (Local) BLAST (local, heuristic) E-value
HMM : Viterbi algorithm - a toy example
MM : Viterbi algorithm - a toy example 0.5 0.5 0.5 A 0.2 A 0.3 0.5 0.6 C 0.3 C 0.2 G 0.3 0.4 G 0.2 T 0.2 T 0.3 et's consider the following simple MM. This model is composed of 2 states, (high GC content)
Hidden Markov Models and some applications
Oleg Makhnin New Mexico Tech Dept. of Mathematics November 11, 2011 HMM description Application to genetic analysis Applications to weather and climate modeling Discussion HMM description Hidden Markov
Comparative Gene Finding. BMI/CS 776 Spring 2015 Colin Dewey
Comparative Gene Finding BMI/CS 776 www.biostat.wisc.edu/bmi776/ Spring 2015 Colin Dewey cdewey@biostat.wisc.edu Goals for Lecture the key concepts to understand are the following: using related genomes
ROBI POLIKAR. ECE 402/504 Lecture Hidden Markov Models IGNAL PROCESSING & PATTERN RECOGNITION ROWAN UNIVERSITY
BIOINFORMATICS Lecture 11-12 Hidden Markov Models ROBI POLIKAR 2011, All Rights Reserved, Robi Polikar. IGNAL PROCESSING & PATTERN RECOGNITION LABORATORY @ ROWAN UNIVERSITY These lecture notes are prepared
Bioinformatics. Proteins II. - Pattern, Profile, & Structure Database Searching. Robert Latek, Ph.D. Bioinformatics, Biocomputing
Bioinformatics Proteins II. - Pattern, Profile, & Structure Database Searching Robert Latek, Ph.D. Bioinformatics, Biocomputing WIBR Bioinformatics Course, Whitehead Institute, 2002 1 Proteins I.-III.
Motivating the need for optimal sequence alignments...
1 Motivating the need for optimal sequence alignments... 2 3 Note that this actually combines two objectives of optimal sequence alignments: (i) use the score of the alignment o infer homology; (ii) use
INTERACTIVE CLUSTERING FOR EXPLORATION OF GENOMIC DATA
INTERACTIVE CLUSTERING FOR EXPLORATION OF GENOMIC DATA XIUFENG WAN xw6@cs.msstate.edu Department of Computer Science Box 9637 JOHN A. BOYLE jab@ra.msstate.edu Department of Biochemistry and Molecular Biology
Alignment principles and homology searching using (PSI-)BLAST. Jaap Heringa Centre for Integrative Bioinformatics VU (IBIVU)
Alignment principles and homology searching using (PSI-)BLAST Jaap Heringa Centre for Integrative Bioinformatics VU (IBIVU) http://ibivu.cs.vu.nl Bioinformatics Nothing in Biology makes sense except in
Sequence analysis and comparison
The aim with sequence identification: Sequence analysis and comparison Marjolein Thunnissen Lund September 2012 Is there any known protein sequence that is homologous to mine? Are there any other species
Dynamic Approaches: The Hidden Markov Model
Dynamic Approaches: The Hidden Markov Model Davide Bacciu Dipartimento di Informatica Università di Pisa bacciu@di.unipi.it Machine Learning: Neural Networks and Advanced Models (AA2) Inference as Message
HIDDEN MARKOV MODELS FOR REMOTE PROTEIN HOMOLOGY DETECTION
From THE CENTER FOR GENOMICS AND BIOINFORMATICS Karolinska Institutet, Stockholm, Sweden HIDDEN MARKOV MODELS FOR REMOTE PROTEIN HOMOLOGY DETECTION Markus Wistrand Stockholm 2005 All previously published
Biological Sequences and Hidden Markov Models CPBS7711
Biological Sequences and Hidden Markov Models CPBS7711 Sept 27, 2011 Sonia Leach, PhD Assistant Professor Center for Genes, Environment, and Health National Jewish Health sonia.leach@gmail.com Slides created