1. Prof. Yechiam Yemini (YY) Computer Science Department Columbia University (c)Copyrights; Yechiam Yemini; 2004-05 Lecture 2: Introduction to Paradigms 2.3 Additional Notes Version: 2.00 1/20/03

2. (c)Copyrights; Yechiam Yemini; 2004-052 A Different Type Example: DNA Microarrays (00)  Brief intro to biology: Central dogma: DNA  RNA  Proteins  Hi-bandwidth experimental biology Microarrays: measure DNA  RNA expression for 25k genes Apps: differential analysis of cell activities  ? Killer app ?: diagnosis, care… 19982005 ?

3. (c)Copyrights; Yechiam Yemini; 2004-053 Probe strands E. Southern: Using Hybridization To Measure Gene Expression Hybridize Target strands + Measurement

4. (c)Copyrights; Yechiam Yemini; 2004-054 (cDNA) Microarray Techniques Data analysis Normalization Image prcssng clustering classification Stat anlyss Machine lrng Biological analysis

5. (c)Copyrights; Yechiam Yemini; 2004-055 Application Example: Cancer Analysis  Alizadeh et al.: “Distinct types of diffuse large B-cell lymphoma identified by gene expression profiling” Nature 403, Feb 2000. Diffuse large B-cell lymphoma (DLBCL), the most common subtype of non-Hodgkin's lymphoma, is clinically heterogeneous: 40% of patients respond well to current therapy and have prolonged survival, whereas the remainder succumb to the disease… ….We identified two molecularly distinct forms of DLBCL which had gene expression patterns indicative of different stages of B-cell differentiation. One type expressed genes characteristic of germinal centre B cells ('germinal centre B-like DLBCL'); the second type expressed genes normally induced during in vitro activation of peripheral blood B cells ('activated B-like DLBCL'). Patients with germinal centre B-like DLBCL had a significantly better overall survival than those with activated B-like DLBCL. The molecular classification of tumours on the basis of gene expression can thus identify previously undetected and clinically significant subtypes of cancer.

6. (c)Copyrights; Yechiam Yemini; 2004-056 Clustering

7. (c)Copyrights; Yechiam Yemini; 2004-057 Discovering Two Types of DLBCL 76% of GC B-like DLBCL patients were still alive after five years, as compared with only 16% of activated B-like DLBCL patients