Class 07: Gene Alignments (2)

Back to Gene Alignments (1). On to Gene Alignments (3).

This outline is also available in PDF.

Held: Thursday, 17 September 2009

Summary: Today we explore the BLAST algorithm in two ways: Through an analysis of the first paper on BLAST and through experiments using an implementation of that algorithm.

Related Pages:

EBoard.
Reading: Altschul et al. 1990: Basic local alignment search tool..
Due: Response to Altschul et al..

Notes:

For next Tuesday: Work on the On Your Own project from Chapter 2.
You will not need to turn in today's Web Exploration.

Overview:

The BLAST Paper.
Simulating the BLAST algorithm by hand.
Web Exporation.

Having a BLAST

Our goal is to tease apart the work represented by the BLAST paper.

Some Standard Questions

What is the problem domain that the paper addresses?
What are the authors' primary claims about their work?
What is the structure of the paper? (Logical, rhetorical, ...)
Why are we reading this paper? What is important about this paper?

Approximate Matching and Searching

The problem seems to be finding all reasonable matches of one sequence in a larger sequence or collection of sequences.
What measurements might we use for reasonable?
What is an MSP (maximal segment pair)?
What is a locally maximal segment pair?
Why do we care about MSPs?
What is an obvious way to find an MSP for two sequences?
What alternatives are there?

The BLAST Algorithm

What are the parameters to the algorithm? (Letters, meanings, ...)
What is the overall structure of the BLAST algorithm? (The authors claim that the algorithm has three stages.)
- Stage 1:
- Stage 2:
- Stage 3:
How do they accomplish each stage?
What is the running time of the algorithm?

Exploring the Algorithm

Helpful tool: PAM Matrix Calculator
Input sequence: AMANAPLANPANAMA
Database: ZZZZZZZZZMANNAFLANNANANAXXXXXXX

How do we generate the word list from the input sequence?
Suppose our word list only contains PLAN and FLAN (everything else is too high frequency).
- How do we search the database?
Suppose we've matched the FLAN (a variant of the middle PLAN with high score)
- How do we expand the word match to an approximate MSP?

Analyzing the BLAST Algorithm

What kinds of analyses are they doing?
Why are they doing these analyses?
What do the analyses suggest?
What are the potential drawbacks of using BLAST?

Web Exploration

Let's all have fun with the Web exploration (using this algorithm we just learned about).

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Samuel A. Rebelsky, rebelsky@grinnell.edu

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