BIOE 582: Statistics & Algorithms in Genomic Biology. What this class is all about?

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1 BIOE 582: Statistics & Algorithms in Genomic Biology What this class is all about?

2 Let me introduce myself Name: Sergei Maslov Professor of Bioengineering, and Physics, faculty at Carl R. Woese Institute for Genomic Biology, and National Center for Supercomputing Applications Office: 3406 IGB and sometimes 3226 DCL Phone:

3 Questions and Suggestions: Start subject with [BIOE582] 11

4 Bring your i clickers to my classes Who knows what is i-clicker? Show of hands: who has an i-clicker? I would like you all to have an i-clicker and bring it to every class. On amazon.com a new i>clicker costs $38. Also sold at UIUC Bookstore. Used are cheaper. Your answers WILL NOT be used for grading. I need it to see if I lost you and what do I need to explain better. New i-clickers need to be registered at

5 We will use Matlab in class Bring your own laptops. Show of hands: who does not have a laptop? Need to have Matlab installed and know the basic interface (inline commands, plotting) Show of hands: who does not have Matlab installed? It is $100 for UIUC students: We will be using: Statistics and Machine Learning Toolbox Bioinformatics toolbox I know it is $100 (greedy Mathworks wants students but not faculty to pay!) but there will be no required textbooks If you miss it in class or want to refresh your memory.m file with Matlab commands will be on the website

6 The main Probability/Statistics Textbook Applied Statistics and Probability for Engineers, 5th Edition D. C. Montgomery and G. C. Runger John Wiley & Sons, Inc. (2011) You can also use other editions from 4 th (2007) to 6 th (2014) 5 th edition is available for free as a Safari ebook at uiu/record/uiu_

7 Probability/Statistics for Bioengineering with Matlab exercises Statistics for Bioengineering Sciences with MATLAB and WinBUGS Support Brani Vidakovic Department of Biomedical Engineering, Georgia Tech (2011) Springer, New York It is constantly updated with the newest version at the link below. Free as a PDF ebook at Matlab exercises and datasets are at 7

8 Genomics/Systems Biology Textbook J Pevsner Bioinformatics and functional genomics Wiley-Blackwell, 2 nd edition [2009] exists in electronic form 3 rd edition [2015] has up-to-date information on NGS: RECOMMENDED (about $60 on amazon) 2 nd edition as PDF in electronic form 8

9 Another Biological Data/Statistics Textbook Ewens, WJ and Grant, GR Statistical Methods in Bioinformatics: An Introduction, 2nd ed, Springer, nd edition as PDF ebook

10 Credit: XKCD comics

11 Why do you need probability and statistics to analyze genomic data?

12 Definition of statistics by Merriam Webster 1 : a branch of mathematics dealing with the collection, analysis, interpretation, and presentation of masses of numerical data

13 Why do you need to know probability and statistics to analyze modern biological data? Reason 1: Genomics has Lots of Data

14 If data was money: $1 investment in 1985 would bring you $1 billion in 2015 J. Pevsner, Bioinformatics and Functional Genomics, 3 rd edition, Wiley Blackwell (2015)

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16 A, C, G, T = 2 bits ~War & Peace 300 Human Genomes 300,000 Human Genomes J. Pevsner, Bioinformatics and Functional Genomics, 3 rd edition, Wiley Blackwell (2015)

17 Who will have bigger data by 2025? Z. Stephens, S. Lee, F. Faghri, R. Campbell, C. Zhai, M. Efron, R. Iyer, M. Schatz, S. Sinha, and G. Robinson (2015) PLoS Biol 13: e

18 One more reason to study hard in this class Glassdoor average salary: Data scientist $118,709 Programmer only $64,537 10

19 What makes genomic data so big? There are ~9 millions species each with its own genome Each of us humans (7.5 billions and counting) has a unique DNA: we want to compare them to each other Each cell has just 1 genome (DNA) but multitude of transcriptomes (RNA levels) and proteomes (protein levels) Cancer cells acquire mutations in their genomes: need to track multiple lineages in a tumor vs time to understand cancer DNA was proposed as a long term storage medium of information

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21 Prof Olgica Milenkovic from Electrical and Computer UIUC is a local expert on this topic Prof. George Church (Harvard Medical School) explains a potential use of DNA as storage medium:

22 Why do you need to know probability and statistics to analyze modern biological data? Reason 2: see video Inner life of the cell Protein packing

23 Show video

24 Inner life of the cell Protein packing Made by the BioVisions Harvard U. led by Dr. Robert A. Lue supported by the Howard Hughes Medical Institute & Harvard Go to for other videos

25 Why do you need to know probability and statistics to analyze modern biological data? Reason 2: Life is random and messy

26 Life is messy, random, and noisy Yet it is beautifully complex

27 Why biological data is so random? Biomolecules are very small (nano to micro meters) Brownian noise Number of molecules per each cell is often small there are large cell to cell variations Genomic data comes from biological evolution the Mother of All Random Processes Genomic data involves (random) samples We have genomes of some (not all) organisms We have tissue samples of some (not all) patients

28 Complex systems have many interacting parts All parts are different from each other 10 thousands (10 4 ) types of proteins in an organism 1 million (10 6 ) routers in the Internet 1 billion (10 9 ) web pages in the WWW 1 billion (10 9 ) people on Facebook 100 billion (10 11 ) neurons in a human brain NOT electrons or quarks: they are all the same! Yet they share the same basic design proteins are strings of the same 20 amino acids WWW pages use HTML, JavaScript, etc. Neurons are cells generating electric spikes

29 Example: a complex system with many parts Justin Pollard, 29

30 Parts interact they need to be assembled to work Justin Pollard, 30

31 Complex systems have networks inside The simplest info: who interacts with whom? Interacting pairs make a network or a graph

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33 Why study networks? Networks are skeletons for dynamical processes taking place inside complex systems Like in paleontology skeletons contain clues about how their owners operate

34 Bionetworks operate at multiple levels Information flow Networks: all to all interactions Regulatory network: RNA level regulation By DNA binding Proteins Protein Protein (binding) Interaction Network Protein Metabolite Interactions: Metabolic network Metabolite (small molecule)

35 Sea urchin embryonic development (from endomesoderm up to 30 hours) by Davidson s lab

36 Protein Protein binding IntAct Database (Dec 2015) Interactions: 577,297 Proteins: 89,716 Baker s yeast S. cerevisiae (only nuclear proteins shown) From S. Maslov, K. Sneppen, Science 2002 Worm C. elegans From S. Lee et al, Science 2004

37 Metabolic pathway chart by ExPASy: 5702 reactions as of December 2015

38 Brain and nerves of a worm Worm (C. elegans) has 302 neurons Our brain has 100 billion (10 11 ) neurons

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40 by Neo Martinez and Richard Williams

41 Networks in technology & engineering

42 Firefox 153 Linux packages required for installation of Firefox TY Pang, S. Maslov, PNAS (2013) 42

43 Network of highways has no hubs

44 Airline networks have hubs

45 Physical backbone of the Internet

46 Credit: XKCD comics