CS 461b/661b: Bioinformatics Tools and Applications

Software

Algorithm

Mathematical Models

Biology Experiments and Data

• Bin Ma

• Title: Associate Professor

• Research area: Bioinformatics

• Office hours: Tuesday 4-5pm, Wednesday 4-5pm.

• Office: MC362

Bioinformatics

Bioinformatics

Class Time

• Monday, MC320, 2:30-4:30pm

• Wednesday, MC320/MC325, 3:30-4:30pm

• Jan. 7. An overview session.

• Jan. 14 (Monday), 16 (Wednesday) will be lectured by Mark Daley.

Evaluation

• Two assignments (10 marks each)

• One project (30 marks)

• One final exam (50 marks)

• TA: ??.

Topic: Whole Genome Shotgun Sequencing

• Sequencing machines are used to read small fragments. Then the “reads” are assembled together.

• How to cut and clone.• How sequencing machines

work.• How to assemble.• DIY: assemble a small

genome.

Topic: PCR and Primer Design

• How to select a region of DNA and make millions of copies rapidly.• How to design the “primers”.• Use it to identify the criminals by FBI and polices.

• DIY: design a primer

Topic: Gene prediction

Gene prediction

• How translation is done

• Gene structures• How to find genes, the

most interesting parts on a genome.

• DIY: find a gene using software.

Topic: NCBI Entrez

• Where to get biological data.

• Use Entrez as a comprehensive data source.

• DIY: download and compare sequences of the same protein in 20 different mammals.

GCNTACACGTCACCATCTGTGCCACCACNCATGTCTCTAGTGATCCCTCATAAGTTCCAACAAAGTTTGC|| ||||| | ||| |||| || |||||||||||||||||| | |||||||| | | |||||GCCTACACACCGCCAGTTGTG-TTCCTGCTATGTCTCTAGTGATCCCTGAAAAGTTCCAGCGTATTTTGC

GAGTACTCAACACCAACATTGATGGGCAATGGAAAATAGCCTTCGCCATCACACCATTAAGGGTGA----|| ||||||||| |||||| | ||||| |||||||| ||| |||||||| | | | || GAATACTCAACAGCAACATCAACGGGCAGCAGAAAATAGGCTTTGCCATCACTGCCATTAAGGATGTGGG

------------------TGTTGAGGAAAGCAGACATTGACCTCACCGAGAGGGCAGGCGAGCTCAGGTA ||||||||||||| ||| ||||||||||| || ||||||| || |||| |TTGACAGTACACTCATAGTGTTGAGGAAAGCTGACGTTGACCTCACCAAGTGGGCAGGAGAACTCACTGA

GGATGAGGTGGAGCATATGATCACCATCATACAGAACTCAC-------CAAGATTCCAGACTGGTTCTTG||||||| |||| | | |||| ||||| || ||||| || |||||| |||||||||||||||GGATGAGATGGAACGTGTGATGACCATTATGCAGAATCCATGCCAGTACAAGATCCCAGACTGGTTCTTG

Topic: BLAST and PatternHunter

sequence alignment

Homology Search

• Use NCBI BLAST as a tool to find similarities.• Spaced seeds.• How to implement the spaced seeds as computer

programs.• DIY: Experiment the sensitivity comparison

between spaced seeds and BLAST seed.

Mass Spectrometry

• Genomics Proteomics• Proteins are more directly related to the functions of cells• Many diseases are closely related to abnormal proteins• Knowing which proteins are present in different cells under

different conditions is useful• Protein ID becomes an essential task in proteomics

Tandem mass spectrometry

• Tandem mass spectrometry (MS/MS, tandem MS) is the standard way for protein identification.

LSIMQDK

peptide tandem mass spectrometer MS/MS spectrum

Mass Spectrometry

• Principles of instruments• Noises and complications in the data• De novo sequencing• SPIDER (de novo sequencing + homology search)• DIY:

– Use a mass spec to identify a protein

– Use PEAKS software to determine a peptide

– Use SPIDER software to identify a protein

High Performance Liquid Chromatography (HPLC)

liquid (water etc.)

to ESI MS/MS

after 20 minutes or so

• DIY: predict the retention time of a few peptides.

Protein Quantitation

• Several different methods for quantitation using mass spec.• DIY: use a spectrum to determine the relative quantity of

two proteins.

Next Generation Sequencing

• How to sequence an individual human’s whole genome (3G bps) in one day, using less than 1000 dollars.

• Huge impact on personalized medicine.