Aalto University
Computational Methods in Genomics

Helpful links

• A brief introduction to molecular biology with emphasis on genomics and bioinformatics Good introduction of molecular biology for CS students.
• What is bioinformatics? NCBI Tutorial.
• Bioinformatics at the Swiss Institute of Bionformatics Good description of how the role of Bioinformatics has evolved over the years.
• An Introduction to the Double Helix.
• A Primer on Molecular Genetics from the U.S. Department of Energy.
• The Human Genome - What's Next? from Current Science and Technology Center.
• Cracking the Code of Life NOVA program. Requires Quick Time or Real Video Plug-in. Recommended segments: 1, 2, 6, 9, 10, 12, 13, 14, and 16.

Information about the Instructor

Registration

Lectures and Hands-on Exercises

Course code and number

Course Description

• The contents of this course are different from the topics of the Summer 2008 course I taught.
• No prior knowledge of Biology is required. In other words, biology is not a prerequisite for this course. But an interest in Biology is. I will spend the first lecture of the course going over some notions in molecular biology (mainly the following Biology Terms) that will be needed for the course.
• We have two rooms at our disposal for the course. The lectures will be given in a lecture hall (TBD) and the hands-on exercises (praticals in British - travaux pratiques in French) will be conducted in the computer lab to be determined. The purpose of the hands-on exercises is to develop your understanding of the material. Please keep your laptops closed during the lectures.

Lecture Material and Schedule

Recommended Textbooks (Not required)

• An Introduction to Bioinformatics Algorithms; by Neil Jones and Pavel Pevzner, MIT Press, 2000.
• Introduction to Computational Molecular Biology; by J. C. Setubal and J. Meidanis. PWS Publishing Company, Boston, 1997.
• Understanding Bioinformatics; by Marketa Zvelebil and Jeremy Baum, Garland Science, 2008.
  
• Bioinformatics and Functional Genomics; by Jonathan Pevsner, John Wiley, 2003.
  
• Bioinformatics: Sequence and Genome Analysis; by David Mount, Cold Spring Harbor Laboratory Press, Second Edition 2004.

Lecture Notes:

• Front Cover
• Introduction: 2 slides per page
• Introduction: 6 slides per page
• Part One: 2 slides per page
• Part One: 6 slides per page
• Part Two: 2 slides per page
• Part Two: 6 slides per page
• Part Three: 2 slides per page
• Part Three: 6 slides per page
• Part Four: 2 slides per page
• Part Four: 6 slides per page

Topics to be covered in the course: (not finalized)

• Micro RNA (miRNA)
  • Seminal Paper:
    David Bartel, 2004. This is an excellent review that highlights what has been learned about miRNAs in the decade since the report of the lin-4 RNA and its regulation of lin-14. The major topics discussed are miRNA genomics, miRNA biogenesis, miRNA regulatory mechanisms, and the roles of miRNAs in gene regulatory pathways. Although outdated (2004), the article is an excellent introduction to miRNAs
  • Carlo Croce, 2008. The main purpose of this article is to show how "The discovery of the involvement of microRNAs in the initiation and progression of human cancer may provide additional targets for anticancer treatments."
  • Fu et al., 2009. The authors use a Markov model to examine base-pairing binding patterns of known microRNA targets.
  • Ken Garber, 2006. A short but very good review on the role of micro RNAs in cancer.

• Microarrays
  • Seminal Paper:
    DeRisi et al., 1997. By using yeast, the authors show how "DNA microarrays provide a simple and economical way to explore gene expression patterns on a genomic scale."
  • Gasch et al., 2000. As a follow-up to DeRisi's work, the authors explore genomic expression patterns in the yeast, by measuring changes in transcript levels over time for almost every yeast gene, of the yeast genome responding to diverse environmental transitions.
  • Alizadeh et al., 2000. The authors use DNA microarrays to conduct a systematic characterization of gene expression in B-cell malignancies and show that there is diversity in gene expression among the tumours of the diffuse large B-cell lymphoma which is the most common subtype of non-Hodgkin's lymphoma.
  • Mark Reimers, 2010. The article describes the typical stages in the analysis of microarray data for nonspecialist researchers in systems biology and medicine.

• Genome-Wide Asociation Studies
  • Seminal Paper:
    Moore et al., 2010. A very recent review on the bioinformatics challenges associated with genome-wide association studies (GWAS).
  • Pearson and Manolio, 2008. A thorough review on genome-wide association studies (GWAS), including a section on terms used in GWAS and a second section on ten basic questions on how to interpret GWAS results.
  • Manolio et al., 2009. The authors examine potential sources of missing heritability. They suggest research strategies, including and extending beyond current genome-wide association approaches, to illuminate the genetics of complex diseases in the hope of enabling effective disease prevention or treatment.
  • Chung et al., 2010. A very recent review on genome-wide association studies (GWAS) in cancer, including curret and future directions of GWAS. The article gives a description of the design, interpretation, application, and also limitations of GWAS.
  • Altshuler et al., 2008. This excellent review discusses "the intellectual foundations of genetic mapping of Mendelian and complex traits in humans, examine lessons emerging from linkage analysis of Mendelian diseases and genome-wide association studies of common diseases, and discuss questions and challenges that lie ahead."

• Next-Generation Sequencing
  • Seminal Paper:
    Horner et al., 2009. A very recent review on the bioinformatics approaches that have been introduced for several genomics and functional genomics applications of next-generation sequencing.
    
  • Rusk and Kiermer, 2007. A one page primer on different sequencing technologies of the next generation; namely: 454, Solexa, and SOLiD technologies.
    
  • Voelkerding et al., 2009. A thorough review on different sequencing technologies of the next generation and their impact on research.

Course Requirements

• Problem Set: One homework assignment. No late homework will be accepted.
  The homework is due in the beginning of the lecture on Wednesday, August 11, 2010.
  The cover sheet for the homework.
  
  
• Term Project: There will be a group project. Each group consists of two students. The group chooses a topic and writes a term-project. A student may work alone if she/he desires not to team up with someone else. The term-project is due by 1700 on September 24, 2010. Please submit your project (hard copy or pdf) to Kalle Karhu. Some guidelines can be found here.

• Hands-On Exercises: (the hands-on exercises will be distributed in class and will not be posted)
  
  
  • Investigating Inherited Diseases:
    The sequences for the hands-on exercise: HandsOn_Sequences.txt
    
    
  • Beta Thalassemia:
    The sequence of the beta globin gene: beta_globin_sequence_handout.txt
    Changes in the Epidemiology of Thalassemia in North America: A New Minority Disease by E. Vichinsky, E. MacKlin, J. Waye, and N. Olivieri, 2005.
    Haemoglobinopathies and glucose-6-phosphate dehydrogenase deficiency in a Scandinavian perspective by E. Theodorsson, H. Birgens and T. Hagve, 2007.
    Specific transcription and RNA splicing defects in five cloned beta Thalassemia genes by R. Treisman, S. Orkin and T. Maniatis, 1983.
    
    
• Exam: In-class, closed notes, and comprehensive on Friday, August 13, 2010, 11:00-12:00.
  

Grading Policy

Homework Assignment: 20%
Hands-On Exercises: 20%
Term Project: 30%
Final Exam: 30%

More Links

• Video about the Human Genome Project. It runs under Window Media Player.
• Finnish Disease Heritage I: characteristics, causes, background by Reijo Norio, 2003.
• Finland's Fascinating Genes by Jeff Wheelwright, 2005.
• Mulibery Nanism: Clinical characteristics and pathophysiologic features of growth restriction, insulin resistance and tumour development PhD Dissertation by Niklas Karlberg, 2009.
• Molecular genetics of Meckel Syndrome Academic Dissertation by Jonna Tallila, 2009.