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); http://dx.doi.org/10.1073/pnas.0607650103
2. Alter, Brown & Botstein, PNAS 100, 3351 (2003); http://dx.doi.org/10.1073/pnas.0530258100
3. Ponnapalli, Saunders, Van Loan and Alter, under review.
4. Omberg, Meyerson, Kobayashi, Drury, Diffley & Alter, Nature MSB 5, 312 (2009); http://dx.doi.org/10.1038/msb.2009.70
5. Alter & Golub, PNAS 101, 16577 (2004); http://dx.doi.org/10.1073/pnas.0406767101
6. Omberg, Golub & Alter, PNAS 104, 18371 (2007); http://dx.doi.org/10.1073/pnas.0709146104
7. Muralidhara, Gross, Gutell & Alter, PLoS One 6, e18768 (2011), http://dx.doi.org/10.1371/journal.pone.0018768
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.
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