Ran Libeskind-Hadas, Department of Computer Science

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Bioinformatics Education at Harvey Mudd College
Ran Libeskind-Hadas, Department of Computer
Science Thanks to Eliot Bush (Biology) and Zach
Dodds (Computer Science)
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Our name is Mudd

• Undergraduate only 700 students
• Sciences, mathematics, and engineering

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Our name is Mudd

• Undergraduate only 700 students
• Sciences, mathematics, and engineering

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Our name is Mudd

• Undergraduate only 700 students
• Sciences, mathematics, and engineering

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The HMC Curriculum
Includes one semester of CS and one of Biology
Electives
Core
Humanities
Major
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Experiments in the Core
Semester 1
Semester 2
Introduction to Biology
200 students per year
Introduction to CS
The regular path
Integrated Introduction to CS and Biology
20 students in 2009-2010
An integrated full year course
Introduction to Biology
or a second Biology course
Computation and Biology
Introduction to Biology
A one semester integrated course
Introduction to Biology
40 students in 2010-2011
Satisfies CS core requirement but not the Biology
requirement
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Computation and Biology Core Course

• Objectives
• Cover the content of the regular CS intro
  course
• Demonstrate the relationship between computing
  and biology
• Use computation to teach biology fundamentals and
  use biology to motivate computing fundamentals
• Provide students with computational tools to
  perform their own dry lab experiments

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Computation and Biology Core Course

• Objectives
• Cover the content of the regular CS intro
  course
• Demonstrate the relationship between computing
  and biology
• Use computation to teach biology fundamentals and
  use biology to motivate computing fundamentals
• Provide students with computational tools to
  perform their own dry lab experiments

9
Computation and Biology Core Course

• Objectives
• Cover the content of the regular CS intro
  course
• Demonstrate the relationship between computing
  and biology
• Use computation to teach biology fundamentals and
  use biology to motivate computing fundamentals
• Provide students with computational tools to
  perform their own dry lab experiments

10
Computation and Biology Core Course

• Objectives
• Cover the content of the regular CS intro
  course
• Demonstrate the relationship between computing
  and biology
• Use computation to teach biology fundamentals and
  use biology to motivate computing fundamentals
• Provide students with computational tools to
  perform their own dry lab experiments

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Course Structure
Assignment
Biologist
Lab!
Tuesday
C.S.ist
Friday
Weekend
CSist
Thursday
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Biology
CS
Subset of student HW
Introduction to Python Data, functions, and
basic constructs
Gene finding, gene expression, lactase expression
DNA, RNA, central dogma, genes Case study of
lactose intolerance
wks 1-3
Mitochondrial Eve, diploid populations with
selection, molecular evolution simulations
Designing a larger program, randomness, simulation
Population genetics, molecular evolution
wks 4-5
Implement alignment and extend to deal with
substitutions
Sequence alignment
Recursion
Wks 6-7
Recursion on trees and phylogenetic tree
algorithms
Implementing a phylogenetic tree algorithm and
making inferences from the results
Phylogenetics
Wks 8-9
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Biology
CS
Subset of student HW
RNA folding algorithm, efficiency, and memoization
Implement RNA folding and visualize results
Folding RNA to Proteins
wks 10-11
Systems biology and modeling Chemotaxis
Wks 11-12
Chemotaxis simulations and evaluation of models
Computation and modeling
Wks 13-14
Capstone Projects
Topics
Limitations of computation
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Using computation to teach biology fundamentals

• Population genetic model
• Explore effects of drift and selection,
• Hardy-Weinberg equilibrium

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Using biology to motivate computation RNA
Folding
Recursion and memoization
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Above and Beyond
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Above and Beyond
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Final project example What makes cholera
pathogenic?

• Pathogenic vs. non-pathogenic strains

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Final project example What makes cholera
pathogenic?

• Compare all genes in one strain with all in other
  to find orthologs (use fast global alignment)

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Final project example What makes cholera
pathogenic?
Programmatically Blast unique proteins to see
what they are

• Read about these unique genes and explain what
  they do

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Microarray data
Courtesy of Prof. Russell Schwartz

• Some genes encode for transcription factors that
  promote or inhibit the expression of other genes
• Purple is highly expressed, green is not
  expressed

genes
conditions
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Intuition Behind Network Inference
Courtesy of Prof. Russell Schwartz
gene 1
0
1
0
1
1
gene 2
0
1
0
1
1
gene 3
1
0
1
0
0
gene 4
0
1
1
0
1
conditions
1
1

-
1

-
2
3
3
2
-
-

2
3
-
1
1


-
-
4
2
3
2
3
-
correlated expression implies common regulation
that intuition still leaves a lot of ambiguity
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Assuming a Binary Input Matrix
Courtesy of Prof. Russell Schwartz

• We will assume that genes only have two possible
  states 0 (off) or 1 (on)
• We will also assume that we want to find
  directionality but not strength of regulatory
  interactions
• We will exclude the possibility of regulatory
  cycles

conditions
gene 1
1
0
1
0
1
1
1
0
1
gene 2
0
0
1
1
1
1
0
gene 3
0
0
1
0
0
0
0
1
gene 4
0
0
0
0
0
1
0
1
1
1
4
4
OK
NOT OK
3
2
3
2
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The Project

• Take binary microarray data as input
• Find the acyclic regulatory network with the
  highest likelihood
• Display the network somehow

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Student Response
Likert scale (1 low, 7 high) survey
This course stimulated my interest in the
subject matter
College mean 5.53/7.0 (std. dev
0.80) Computation and Biology 6.51/7.0
I learned a great deal in this course
College mean 5.76/7.0 (std. dev
0.72) Computation and Biology 6.49/7.0
Time spent outside of class (per week)
College mean 4.98 hours (std. dev
2.42) Computation and Biology 6.28 hours
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What did students choose to do the following term?
Students have one elective in the spring
term Took introductory biology 0/40 Took
an elective other than CS or biology
0/40 Took an upper division biology course
18/40 Took the second CS course 22/40
Outperformed their peers
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• Students learned the foundational content of
• Intro CS and Intro Biology
• Students programs provide rich dry lab
  experiments
• and simulations that reinforce understanding of
  biology
• Students develop general problem-solving and
• programming skills (e.g. DP) and have
  confidence to
• solve new problems on their own

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• Students learned the foundational content of
• Intro CS and Intro Biology
• Students programs provide rich dry lab
  experiments
• and simulations that reinforce understanding of
  biology
• Students develop general problem-solving and
• programming skills (e.g. DP) and have
  confidence to
• solve new problems on their own

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• Students learned the foundational content of
• Intro CS and Intro Biology
• Students programs provide rich dry lab
  experiments
• and simulations that reinforce understanding of
  biology
• Students develop general problem-solving and
• programming skills (e.g. DP) and have
  confidence to
• solve new problems on their own

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Next steps

• Increasing student demand for more courses and
  even a major in computational biology
• Mathematical Biology Major redesigned in Spring
  2011 to Mathematical and Computational Biology
  (MCB) major
• Good news 9 MCB majors in sophomore year
• (6 Biology majors and 2 Biochemistry majors)
• Bad news Few faculty in a position to
  contribute

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Beyond the core (intro CS, intro Biology, 3
semesters math, 2 chemistry, 1 physics, )

• Introductory Sequence
• Discrete Math
• Biology laboratory
• Introduction to Mathematical and Computational
  Biology
• Biology Foundations
• Three of Comparative physiology, ecology and
  environmental biology, evolutionary biology,
  molecular biology
• One biology seminar
• One biology laboratory
• Mathematical and Computation Courses
• Intermediate Mathematical Biology
• Computational Biology
• One upper-division math course
• One upper-division CS course
• Three more math and CS courses

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Future Plans

• Refine and improve introductory course
• Write a book for the introductory course
• Collaborate with sister institutions to expand
  computational biology curriculum
• New faculty
• New courses

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Questions, Comments, Heckles