1. Sequence Alignment and Modeling System (SAM) UC, Stata Cruz

2. Quick Overview What is can do? Modeling, aligning and discriminating biological sequences (DNA, RNA, protein) Given A set of biological sequences (regard as ‘related’) SAM-T2K This method is available in SAM 3.0 or higher, used to build a linear HMM representing the given set

3. Linear HMM The model is a linear sequence of nodes, including match (square), insert (diamond) and delete (circle)

4. Applications and Contributions Protein structure prediction It is also an Automatic entries to CASP5 (SAM-T99, SAM-T02) and CASP4 (SAM-T99) Yeast (S. cerervisiae) protein predictions SCOP super-family search and alignment library (not work now) Program update SAM-T98  SAM-T99  SAM-T02 22 publications

5. CASP Critical Assessment of techniques for Protein Structure Prediction Once 2 years CASP1 (1994) CASP2 (1996) CASP3 (1998) CASP4 (2000) CASP5 (2002) CASP6 (2004) CASP7 (2006), coming soon!

6. Program Structure (version 3.5) Test set Related sequences Aligned sequences modelfromalign buildmodel Library of aa distribution Preliminary model Evaluate HMM model align2modelhmmscore Protein DB Refine model Fine-tuned HMM model (1) (2) (3) (1) (2) MSA resultsPossible members

7. Primary programs Build a model buildmodel (from unaligned sequences) modelfromalign (from aligned sequences) Exeaming models makelogo and drawmodel Perform MSA align2model and prettyalign Scoring Sequences hmmscore Choose ‘significant’ sequence entries by 2 scores target2k Use one sequence as ‘seed’ to iteratively create model

8. Assignment Data Obtain a set of close related sequences, split into 2 parts: training and testing Hint: check known protein families Procedure Build a model for training set Evaluate the model by testing set Search all possible via HMM-based DB search Multiple alignment ‘given’ and ‘found’ Please read sam_doc.pdf (full manual)