Gabriele Antoniazzi

966494
Class discovery in gene expression data: applications to cancer research
Class discovery analysis is a gene expression analysis used to discover groups of genes or groups of
samples that display similar behaviors or common patterns from transcriptomics experiments . This
kind of analysis has become especially important in the study of pathologies allowing to obtain a
deeper understanding of the pathogenesis and molecular mechanisms, underlining the fact that
patients of the same disease differ one to the other with the need of personalized therapies, moving
towards the concept of personalized medicine.
The approaches are two basically:

The first one is to identify classes of genes that possess similar expression profiles across different
tissues or conditions; often genes that share a common expression pattern in time or among tissues
are involved in similar or related biological processes and this can become relevant for functional
genomics study of the disease.

The second approach is to identify classes of samples (es. patients) with a similar transcriptome
meaning that among cells and tissues, we can find shared patterns in their transcriptomic profile that
may carry a hidden connection with relevance to the human disease. This can become really
important to the molecular classification of pathologies suggesting possible molecular subtypes
within the same disease

Among the techniques used to obtain this data there are Clustering algorithms that are able to, given
the results of a transcriptomic experiment, obtain groups of genes that possess similar transcriptomic
profile or that are co-expressed. Algorithms can also be used to do a Hierarchical clustering which
does not regroup genes but instead builds a binary rooted tree exactly like the ones used in
phylogenetic analysis where, from the principal root containing all genes, detach “branches” of
clusters with shared characteristics.
It has to be clear that even if these algorithms are used and created in the context of biology
investigation, the results they give us have no direct biological meaning; they remain a
mathematical tool that help us visualize big data, but still, the results have to be interpreted.
This analysis approach has been incredibly useful for the research in the past years; in particular in
the cancer field where it allowed a deeper characterization of differences that can be found within
the same cancer in patients leading to better and aimed treatments.
An example can be Alizadeh et. al that studied Diffuse large B-cell lymphoma which is clinically
highly heterogeneous; 40% of patients respond well to therapy whereas the remain percentage
usually don’t, facing relapse and succumbing to the disease. They proposed that this high
variability was due to yet unrecognized molecular heterogeneity between tumors. Using DNA
microarrays and trough gene expression profiling assays they assessed two molecularly distinct
forms of DLBCL with different expression patterns correlated with different survival rates.
Another example is the study by Bittner et. al conducted on melanomas for which at that time no
accepted histopathological, molecular or immunohistochemical marker was available to better
define melanomas.. They propose that a previously unrecognized cancer taxonomy exist and can be
identifyed by systematically analysis of data and hierarchical clustering from gene expression
experiments. Significant efforts led to identify predictors of melanoma outcome trough
mathematical analysis of gene expression identifying unrecognized subtypes of cutaneous
melanomas with differentially regulated genes.
 Gabriele Antoniazzi
966494
REFERENCES

Ben-Dor, Amir, Nir Friedman, and Zohar Yakhini. "Class discovery in gene expression
data." Proceedings of the fifth annual international conference on Computational biology.
2001.

Dudoit, Sandrine, Jane Fridlyand, and Terence P. Speed. "Comparison of discrimination

methods for the classification of tumors using gene expression data." Journal of the
American statistical association 97.457 (2002): 77-87.

Alizadeh, Ash A., et al. "Distinct types of diffuse large B-cell lymphoma identified by gene
expression profiling." Nature 403.6769 (2000): 503-511.

Bittner M, Meltzer P, Chen Y, Jiang Y, Seftor E, Hendrix M, Radmacher M, Simon R,

Yakhini Z, Carpten J, Gillanders E, Leja D, Dietrich K, Beaudry C, Berens M, Alberts D,
Sondak V. Molecular classification of cutaneous malignant melanoma by gene expression
profiling. Nature. 2000 Aug 3;406(6795):536-40. doi: 10.1038/35020115. PMID: 10952317.