Discovery of Mechanisms and Prognosis of Cancers from Matrix and Tensor Modeling of Large-Scale Molecular Biological Data

Orly Alter
University of Utah

In my Genomic Signal Processing Lab, we believe that future discovery and control in biology and medicine will come from the mathematical modeling of large-scale molecular biological data, such as DNA microarray data, just as Kepler discovered the laws of planetary motion by using mathematics to describe trends in astronomical data [1].
In this talk, I will first describe novel generalizations of the matrix and tensor computations that underlie theoretical physics (e.g., [2,3]), that we are developing for comparison and integration of multiple genomic datasets recording different aspects of, e.g., the cell division cycle and cancer. Second, I will describe our recent experiments [4] that verify a computationally predicted genome-wide mode of regulation [5,6], and demonstrate that singular value decomposition (SVD) and higher-order SVD (HOSVD) modeling of DNA microarray data can be used to correctly predict previously unknown cellular mechanisms.
Third, I will show that mode-1 HOSVD modeling of rRNA sequence alignments suggests a new way of looking at evolution as a composition of changes rather than a hierarchy of changes, and might be used to predict evolutionary mechanisms, i.e., evolutionary pathways and the underlying structural changes that these pathways are correlated, possibly even coordinated with [7]. Last, I will describe the computational prognosis of brain cancers by using generalized SVD to compare global DNA copy numbers in patient-matched normal and tumor samples from the Cancer Genome Atlas [8,9].

1. Alter, PNAS 103, 16063 (2006);

2. Alter, Brown & Botstein, PNAS 100, 3351 (2003);

3. Ponnapalli, Saunders, Van Loan and Alter, under review.

4. Omberg, Meyerson, Kobayashi, Drury, Diffley & Alter, Nature MSB 5, 312 (2009);

5. Alter & Golub, PNAS 101, 16577 (2004);

6. Omberg, Golub & Alter, PNAS 104, 18371 (2007);

7. Muralidhara, Gross, Gutell & Alter, PLoS One 6, e18768 (2011),

8. Lee & Alter, 60th Annual Meeting of the American Society of Human Genetics (Washington, DC, November 2-6, 2010).

9. Lee, Alpert, Sankaranarayanan & Alter, under review.

Presentation (PDF File)

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