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INTERDISCIPLINARY QUANTITATIVE
REASONING IN BIOLOGY EDUCATION
26 March 2014
John R. Jungck
BioQUEST Curriculum Consortium
Editor, Biology International, International Union of Biological Sciences
Professor of Biological & Mathematical Sciences, University of Delaware, USA
Director, Interdisciplinary Sciences Learning Laboratories
jungck@udel.edu <http://bioquest.org>
Examples:
Population Size
(Capture-Mark-Recapture)
Buffer Preparation
(Henderson-Hasselbach)
Serial Dilution
(Enumerating Bacteria)
Allele Frequencies
(Classroom Data)
Modeling More Mold
Measuring the area covered by mold over intervals of time!
Image J Measurement
“Exponential growth and then levels off” - Microbio Teacher!
Robert Blystone
Trinity University
Ka-me: A Voronoi Image Analyzer
Bioinformatics (2012)
Problem	
  for	
  
today:	
  
	
  
How	
  do	
  we	
  
understand	
  
biological	
  
tessella7ons	
  that	
  
are	
  produced	
  by	
  
several	
  rounds	
  of	
  
successive	
  cell	
  
division?	
  
Richard	
  Jones	
  
Mito7c	
  Division	
  2	
  
Abstract!
Bibliography!
What happens when?
•  Your ruler doesn’t
seem to work right?
•  Your mean and
variance don’t
agree with another
published study?
•  Duplicates of
experiments vary
widely?
Fractal Measurements
•  Rulers
•  Box Plots
•  Concentric Annuli
•  Log-Log Plots
Fractal Dimension Calculator
Written by Paul Bourke (February 2003)
• Bacterial colonies exhibit complex growth patterns on starvation
conditions (Shane Stafford and Yan Li:):!
• Experimentally:!
• The growth pattern and fractal dimension depend on both the
nutrient concentration and roughness of the agar substrate !
• Bacteria perform a random walk like movement on the substrate,
within a well-defined envelope (lubrication layer)!
• Under extreme adverse living conditions, patterns become dense
again by chemo tactic signaling!
E Ben-Jacob et al, Nature,368, (47)1994,!
Fractal Bacterial Growth
Fractal Dimension of Healthy and
Leukemic Cells
Dangers of Linear Transformations:!
Michaelis-Menten Enzyme kinetics!
-d[S]/dt = Vmax[S]/KM + [S]!
Computational Complexity
EBI: “Important: We kindly ask all users of EMBL-EBI Web Services to submit tool jobs in batches of up
to 25 at a time and to not submit more until the results and processing has completed for these. This enables
users as well as the service maintainers to deal more easily with local and remote network outages as well as
scheduled or unscheduled downtime.”
Visualization
 visualization + equations + simulations
lead to better understanding
 aesthetic aspects attract attention
 examples: WWW, images, toys, gadgets
Barbara Maria Stafford!
!
!
“What is lacking today, however, is a concomitant!
high-level visual education to accompany the!
advances in visualization”!
!
!
!
Artful Science: Enlightenment, Entertainment and the!
Eclipse of Visual Education, MIT Press (1994)!
Hans Rosling and Gapminder:
provide resources for context
www.gapminder.org	
  
Gapminder: Goal to make data
accessible and understandable
•  What’s here: Gapminder WORLD from
UNICEF
Health vs Wealth
Visualizing Data
www.gapminder.org/
Starvation Plot
BIRDD:
Species with regard to Wing Length
Upper Beak Length and Beak Height
http://people.eku.edu/ritchisong/
RITCHISO//DarwinsFinches.jpg
Evolution class yesterday: Jared Wynne, David Meltzer, and Aaron Nesser
Arthur Nature Reviews Genetics;
11 April 2006
Bioorthogonal Transformations!
Scaling and
shear
transformations
capture beak
shape variation
in Darwin’s
finches.
O. Camp , R.
Mallarinob, A.
Herrelb, A.
Abzhanovb, and
M. P. Brennera/
School of
Engineering and
Applied
Sciences,
Harvard
University
and Department
of Organismic
and Evolutionary
Biology, Harvard
University
D’Arcy Wentworth Thompson:
Linear
D’Arcy Wentworth Thompson:
Affine
D’Arcy Wentworth Thompson:
Quadratic
STEM TO STEAM
http://
www.steamedu.co
Richard Dawkins & Lalla Ward (“Dr.
Who”)
(1994)!
Seeing is:
•  Doing
•  Measuring
•  Testing hypotheses
•  Re-visioning
•  Modeling
SequenceIt!
 COMBINATORIAL EXPLOSION
 19! = 1.22 * 1017
 opportunity for “infinite opportunity” to
do research
 heuristics vs. algorithms
 realism: run out of material; improperly
designed experiments = poor results
Mastermind
Mastermind Mathematics:
Logic, Strategies, and Proofs
by Mathew Mitchell.
Key Curriculum Press.
Mathematics teachers have long used the game MASTERMIND to
teach logic and deduction. Mathew Mitchell, an associate
professor at the University of San Francisco Department of
Learning and Instruction, makes the connections between
game strategies and mathematics concepts such as problem-
solving and proof strategies. As students use this book and
play MASTERMIND, apply strategies such as establishing
subgoals, making a chart, deductive reasoning, eliminating
possibilities, pattern searching, and proof by contradiction.
http://www.maa.org/mathland/mathtrek_10_11_99.html	

Ivars Peterson’s Math Trek column on math & “Mastermind.”
Done by an undergraduate
Alfred Henry Sturtevant 1891-1970
First Ever Genetic Map - Drosophila X-chromosome!
3!
Linkage Analysis
in the
Biological ESTEEM Project
Excel Simulations and Tools for
Exploratory, Experiential
Mathematics
Benzer 1959, 1961 papers:
topology and topography of
genetic fine structure
•  Topography paper:
–  map several thousand point mutations using nested set of deletion alleles
–  note difference between spontaneous and induced mutations, first detailed analysis of
mutagen specificity
javaBENZER Problem Solving Tools:
Solve Problem = rearranges Shkurba (Mut) into Shkurba form
with all Maximal Cliques ordered on main diagonal
Applications: Protein and Nucleic Acid Sequencing;
Restriction, Deletion, and Complementation Mapping;
Microarray Gene Expression Data; Food Webs
My interactive solution 	

 	

Computer algorithm solution	

Lower right to upper left is isomorphic to upper left to lower right
Phylogenetic Trees
Fitch, W.M. and Margoliash, E. 1967. The construction of phylogenetic trees - a
generally applicable method utilizing estimates of the mutation distance
obtained from cytochrome c sequences. Science 155: 279-284.
Walter M. Fitch Emmanuel Margoliash
4!
4!
Graph Theory: Phylogenetic Trees!4!
An example problem using
Phylogenetic Analysis
•  1990: HIV+ dentist in Florida
•  several patients also HIV+
•  was the dentist the source?
•  some patients with other HIV risk
factors
•  virus from dentist, patients, others
•  evolutionary relationships of virus gp120
gene → transmission of virus
4!
CDC Conclusion
Dentist Patient Patient Patient Other Other Other
Split Decomposition:
Evaluate Evidence for Internal Branches
Alpha !AAGAAGCAGGGGCTGGAGATGAAGGCCCATG!
Beta !AAGAAGCGGAGGCTGGAGCTGAAGGCCCATG!
Gamma !AAGAAGCGGAGGGTGGAGCTGAAGGCCCACG!
Delta !GAGAAGAGGAGCCTGGAGCTGAAGGCCCACA!
Three possible unrooted trees:
A
B
G
D
A
G
B
D
A
D
B
G
Alpha !AAGAAGCAGGGGCTGGAGATGAAGGCCCATG!
Beta !AAGAAGCGGAGGCTGGAGCTGAAGGCCCATG!
Gamma !AAGAAGCGGAGGGTGGAGCTGAAGGCCCACG!
Delta !GAGAAGAGGAGCCTGGAGCTGAAGGCCCACA!
A
B
G
D
dAB
dGD
dAG
dBD
dcentral =
dcentral
2
ONLY for the
correct tree!!!
How can we calculate
the length of the
central branch?
dAB
dGD
dAG + dBD - ( dAB + dGD )
Split Decomposition
Which tree topology is most consistent with the data?
The Algorithmic Beauty of Sea
Shells
Biological Cellular Automata
Laboratory (BioCA Lab)
Author(s): John Jungck, University of Delaware
Jennifer Spangenberg, Washington State University
Nobel Prize 1969
Salvador Luria Max Delbrück
1924-1998 1919-2004
“Fluctuation Test” Poisson Statistics Mutation Rates!
Darwin vs Lamarck!
Considered by many as the finest experiment in 20th Century!
9!
FLUCTUATION TEST
A TEST OF DARWINISM VS LAMARCKISM
Genetics Construction Kit
  Gene Interaction
1:2:1:2:4:2:1:2:1 3:6:3:1:2:1 9:3:3:1
  Epistasis
9:3:4 9:7 15:1 13:3 12:3:1
  Polygenes
1:4:6:4:1
  Quasi-quantitative
10:5:1 11:4:1 11:2:2:1
Genetics Construction Kit
(the integrated organismal model)
 Linkage (Haldane Function)
 Multiple Loci/ Stochasticity 1-10
 Multiple Alleles 1-5
 Sex-linkage, Sex-limited, Sex-influenced
 Gene Interaction/Polygenes/Epistasis
 Monoecious/Dioecious
 Lethality/Penetrance/Pleiotropy
3!
Beer-Lambert law,
E. O. Wilson
Robert MacArthur
Island
Biogeography
Theory
Allometry
Species-Area-
Distance-Law
8!
Source of most CONSEVATION
strategies and policies!
Island Biogeography: Species-Area Law!
“Bacterial genetic diversity in this system increased with increasing island size according to the familiar
species-area power law (Fig. 1A). The slope z of the relationship (z = 0.26) is indistinguishable from published
values for larger organisms (Fig. 1B). The data show that area size strongly influences the diversity of these
microbial communities.” (Bell et al. 2005 Science 308:1884).
Spatial scaling of bacteria in water-filled treeholes
Lee Segel Prize for Best Paper 2010
Brynja R. Kohler, Rebecca J. Swank, James W.
Haefner, James A. Powell.
"Leading Students to Investigate Diffusion as a Model
of Brine Shrimp Movement”
Bull. Math. Biol. 72: 230-57 (2010).
Society for Mathematical Biology
Invade	
  the	
  Biology	
  Lab!	
  
SMB Lee Segel Prize

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CRI - Teaching Through Research - John Jungck - BioQuest

  • 1. INTERDISCIPLINARY QUANTITATIVE REASONING IN BIOLOGY EDUCATION 26 March 2014 John R. Jungck BioQUEST Curriculum Consortium Editor, Biology International, International Union of Biological Sciences Professor of Biological & Mathematical Sciences, University of Delaware, USA Director, Interdisciplinary Sciences Learning Laboratories jungck@udel.edu <http://bioquest.org>
  • 2.
  • 3. Examples: Population Size (Capture-Mark-Recapture) Buffer Preparation (Henderson-Hasselbach) Serial Dilution (Enumerating Bacteria) Allele Frequencies (Classroom Data)
  • 4.
  • 5. Modeling More Mold Measuring the area covered by mold over intervals of time!
  • 7. “Exponential growth and then levels off” - Microbio Teacher!
  • 9.
  • 10. Ka-me: A Voronoi Image Analyzer Bioinformatics (2012)
  • 11. Problem  for   today:     How  do  we   understand   biological   tessella7ons  that   are  produced  by   several  rounds  of   successive  cell   division?   Richard  Jones  
  • 13.
  • 15.
  • 16. What happens when? •  Your ruler doesn’t seem to work right? •  Your mean and variance don’t agree with another published study? •  Duplicates of experiments vary widely?
  • 17. Fractal Measurements •  Rulers •  Box Plots •  Concentric Annuli •  Log-Log Plots Fractal Dimension Calculator Written by Paul Bourke (February 2003)
  • 18. • Bacterial colonies exhibit complex growth patterns on starvation conditions (Shane Stafford and Yan Li:):! • Experimentally:! • The growth pattern and fractal dimension depend on both the nutrient concentration and roughness of the agar substrate ! • Bacteria perform a random walk like movement on the substrate, within a well-defined envelope (lubrication layer)! • Under extreme adverse living conditions, patterns become dense again by chemo tactic signaling! E Ben-Jacob et al, Nature,368, (47)1994,! Fractal Bacterial Growth
  • 19.
  • 20.
  • 21. Fractal Dimension of Healthy and Leukemic Cells
  • 22.
  • 23. Dangers of Linear Transformations:! Michaelis-Menten Enzyme kinetics! -d[S]/dt = Vmax[S]/KM + [S]!
  • 24. Computational Complexity EBI: “Important: We kindly ask all users of EMBL-EBI Web Services to submit tool jobs in batches of up to 25 at a time and to not submit more until the results and processing has completed for these. This enables users as well as the service maintainers to deal more easily with local and remote network outages as well as scheduled or unscheduled downtime.”
  • 25.
  • 26.
  • 27. Visualization  visualization + equations + simulations lead to better understanding  aesthetic aspects attract attention  examples: WWW, images, toys, gadgets
  • 28. Barbara Maria Stafford! ! ! “What is lacking today, however, is a concomitant! high-level visual education to accompany the! advances in visualization”! ! ! ! Artful Science: Enlightenment, Entertainment and the! Eclipse of Visual Education, MIT Press (1994)!
  • 29. Hans Rosling and Gapminder: provide resources for context www.gapminder.org  
  • 30. Gapminder: Goal to make data accessible and understandable •  What’s here: Gapminder WORLD from UNICEF
  • 34.
  • 35. BIRDD: Species with regard to Wing Length Upper Beak Length and Beak Height http://people.eku.edu/ritchisong/ RITCHISO//DarwinsFinches.jpg Evolution class yesterday: Jared Wynne, David Meltzer, and Aaron Nesser
  • 36.
  • 37. Arthur Nature Reviews Genetics; 11 April 2006 Bioorthogonal Transformations!
  • 38. Scaling and shear transformations capture beak shape variation in Darwin’s finches. O. Camp , R. Mallarinob, A. Herrelb, A. Abzhanovb, and M. P. Brennera/ School of Engineering and Applied Sciences, Harvard University and Department of Organismic and Evolutionary Biology, Harvard University
  • 44.
  • 45. Richard Dawkins & Lalla Ward (“Dr. Who”) (1994)!
  • 46. Seeing is: •  Doing •  Measuring •  Testing hypotheses •  Re-visioning •  Modeling
  • 47.
  • 48. SequenceIt!  COMBINATORIAL EXPLOSION  19! = 1.22 * 1017  opportunity for “infinite opportunity” to do research  heuristics vs. algorithms  realism: run out of material; improperly designed experiments = poor results
  • 49. Mastermind Mastermind Mathematics: Logic, Strategies, and Proofs by Mathew Mitchell. Key Curriculum Press. Mathematics teachers have long used the game MASTERMIND to teach logic and deduction. Mathew Mitchell, an associate professor at the University of San Francisco Department of Learning and Instruction, makes the connections between game strategies and mathematics concepts such as problem- solving and proof strategies. As students use this book and play MASTERMIND, apply strategies such as establishing subgoals, making a chart, deductive reasoning, eliminating possibilities, pattern searching, and proof by contradiction. http://www.maa.org/mathland/mathtrek_10_11_99.html Ivars Peterson’s Math Trek column on math & “Mastermind.”
  • 50.
  • 51. Done by an undergraduate Alfred Henry Sturtevant 1891-1970 First Ever Genetic Map - Drosophila X-chromosome! 3!
  • 52. Linkage Analysis in the Biological ESTEEM Project Excel Simulations and Tools for Exploratory, Experiential Mathematics
  • 53. Benzer 1959, 1961 papers: topology and topography of genetic fine structure •  Topography paper: –  map several thousand point mutations using nested set of deletion alleles –  note difference between spontaneous and induced mutations, first detailed analysis of mutagen specificity
  • 54. javaBENZER Problem Solving Tools: Solve Problem = rearranges Shkurba (Mut) into Shkurba form with all Maximal Cliques ordered on main diagonal Applications: Protein and Nucleic Acid Sequencing; Restriction, Deletion, and Complementation Mapping; Microarray Gene Expression Data; Food Webs My interactive solution Computer algorithm solution Lower right to upper left is isomorphic to upper left to lower right
  • 55.
  • 56. Phylogenetic Trees Fitch, W.M. and Margoliash, E. 1967. The construction of phylogenetic trees - a generally applicable method utilizing estimates of the mutation distance obtained from cytochrome c sequences. Science 155: 279-284. Walter M. Fitch Emmanuel Margoliash 4!
  • 57. 4!
  • 59. An example problem using Phylogenetic Analysis •  1990: HIV+ dentist in Florida •  several patients also HIV+ •  was the dentist the source? •  some patients with other HIV risk factors •  virus from dentist, patients, others •  evolutionary relationships of virus gp120 gene → transmission of virus 4!
  • 60. CDC Conclusion Dentist Patient Patient Patient Other Other Other
  • 61. Split Decomposition: Evaluate Evidence for Internal Branches Alpha !AAGAAGCAGGGGCTGGAGATGAAGGCCCATG! Beta !AAGAAGCGGAGGCTGGAGCTGAAGGCCCATG! Gamma !AAGAAGCGGAGGGTGGAGCTGAAGGCCCACG! Delta !GAGAAGAGGAGCCTGGAGCTGAAGGCCCACA! Three possible unrooted trees: A B G D A G B D A D B G
  • 62. Alpha !AAGAAGCAGGGGCTGGAGATGAAGGCCCATG! Beta !AAGAAGCGGAGGCTGGAGCTGAAGGCCCATG! Gamma !AAGAAGCGGAGGGTGGAGCTGAAGGCCCACG! Delta !GAGAAGAGGAGCCTGGAGCTGAAGGCCCACA! A B G D dAB dGD dAG dBD dcentral = dcentral 2 ONLY for the correct tree!!! How can we calculate the length of the central branch? dAB dGD dAG + dBD - ( dAB + dGD )
  • 63. Split Decomposition Which tree topology is most consistent with the data?
  • 64. The Algorithmic Beauty of Sea Shells
  • 65. Biological Cellular Automata Laboratory (BioCA Lab) Author(s): John Jungck, University of Delaware Jennifer Spangenberg, Washington State University
  • 66.
  • 67. Nobel Prize 1969 Salvador Luria Max Delbrück 1924-1998 1919-2004 “Fluctuation Test” Poisson Statistics Mutation Rates! Darwin vs Lamarck! Considered by many as the finest experiment in 20th Century! 9!
  • 68. FLUCTUATION TEST A TEST OF DARWINISM VS LAMARCKISM
  • 69. Genetics Construction Kit   Gene Interaction 1:2:1:2:4:2:1:2:1 3:6:3:1:2:1 9:3:3:1   Epistasis 9:3:4 9:7 15:1 13:3 12:3:1   Polygenes 1:4:6:4:1   Quasi-quantitative 10:5:1 11:4:1 11:2:2:1
  • 70. Genetics Construction Kit (the integrated organismal model)  Linkage (Haldane Function)  Multiple Loci/ Stochasticity 1-10  Multiple Alleles 1-5  Sex-linkage, Sex-limited, Sex-influenced  Gene Interaction/Polygenes/Epistasis  Monoecious/Dioecious  Lethality/Penetrance/Pleiotropy 3!
  • 72. E. O. Wilson Robert MacArthur Island Biogeography Theory Allometry Species-Area- Distance-Law 8! Source of most CONSEVATION strategies and policies!
  • 74. “Bacterial genetic diversity in this system increased with increasing island size according to the familiar species-area power law (Fig. 1A). The slope z of the relationship (z = 0.26) is indistinguishable from published values for larger organisms (Fig. 1B). The data show that area size strongly influences the diversity of these microbial communities.” (Bell et al. 2005 Science 308:1884). Spatial scaling of bacteria in water-filled treeholes
  • 75. Lee Segel Prize for Best Paper 2010 Brynja R. Kohler, Rebecca J. Swank, James W. Haefner, James A. Powell. "Leading Students to Investigate Diffusion as a Model of Brine Shrimp Movement” Bull. Math. Biol. 72: 230-57 (2010). Society for Mathematical Biology
  • 76. Invade  the  Biology  Lab!   SMB Lee Segel Prize