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Orly Alter

Current Research

NCI U01 CA-202144: Multi-Tensor Decompositions for Personalized Cancer Diagnostics and Prognostics1

Inventors of the "eigengene,"2,3,4,5,6,7,8  we formulate comparative spectral decompositions, physics-inspired9,10,11,12,13,14  multi-tensor15,16  generalizations17,18,19,20,21  of the singular value decomposition, to (i) compare and integrate any data types, of any number and dimensions, and (ii) scale with data sizes. Our models (iii) are interpretable in terms of known biology and batch effects and (iv) correctly22  predict23,24,25,26,27  previously unknown mechanisms.28,29,30  By validating a genome-wide pattern of DNA copy-number alterations in brain31,32,33,34,35  tumors as the best predictor of life expectancy and standard of care, our retrospective clinical trial36,37  proved that the models (v) discover accurate, precise, and actionable genotype-phenotype relationships, (vi) are relevant to populations based upon whole genomes of small cohorts, and (vii) can be validated. We discovered this, and patterns in lung,38,39  nerve, ovarian,40,41,42,43,44,45  and uterine tumors, in public data. Such alterations were recognized in cancer, yet repeated previous attempts to associate them with outcome failed, demonstrating that our algorithms are uniquely suited to personalized medicine.

In the News

  1. Mention: Among the most shared Applied Physics Letters (APL) Bioengineering research as of 2021, APL Bioengineering (October 30, 2021).

  2. Press Release: J. Kiefer, "Genome-Wide Pattern Found in Tumors from Brain Cancer Patients Predicts Life Expectancy," American Association for the Advancement of Science (AAAS) EurekAlert! (May 15, 2020).

  3. Mention: Among the top 10 most downloaded Applied Physics Letters (APL) Bioengineering articles as of 2019, APL Bioengineering (May 14, 2019).

  4. Feature: A. J. Engler and D. E. Discher, "Rationally Engineered Advances in Cancer Research," Applied Physics Letters (APL) Bioengineering 2 (3), Special Topic: Bioengineering of Cancer preface 031601 (September 2018).

  5. Mention: Among the top 10% most cited Public Library of Science (PLoS) One articles as of 2017, PLoS One (June 30, 2017).

  6. Feature: F. Pavlou, "Big Data, Hidden Knowledge," The Pathologist (June 15, 2015).46

  7. Feature: R. Atkins, "Calculating Cancer Cures," National Academy of Engineering (NAE) Innovation Podcast and Radio Series (April 19, 2015).47

  8. Press Release: J. Kiefer, "New Method Increases Accuracy of Ovarian Cancer Prognosis and Diagnosis," American Association for the Advancement of Science (AAAS) EurekAlert! (April 15, 2015).

  9. Recommendation: M. Méchali, Faculty Opinions recommendation 1728974 (February 2010).

  10. Feature: S. N. Dwivedi, "Rao Conference at the Interface between Statistics and the Sciences (Hyderabad, India, December 30, 2009 – January 2, 2010), Rao Best Poster Prize," International Biometric Society (IBS) Bulletin 27 (1), pp. 6–7 (January–March 2010).

  11. Press Release: B. Rische, "Mathematical Modeling Correctly Predicts Previously Unknown Biological Mechanism of Regulation," American Association for the Advancement of Science (AAAS) EurekAlert!(October 13, 2009).

  12. Excerpt: O. Alter, International Linear Algebra Society (ILAS) Linear Algebra and its Applications (LAA) Lecture, "Genomic Signal Processing: From Matrix Algebra to Genetic Networks," IMAGE: ILAS Bulletin35, pp. 2–15 (December 2005).48

  13. Feature: National Research Council, Mathematics and 21st Century Biology. Washington, DC: National Academies Press (July 2005), 149 pp.

  14. Feature: M. E. Kilmer and C. D. Moravitz Martin, "Decomposing a Tensor," Society for Industrial and Applied Mathematics (SIAM) News 37 (9), (November 2004).49

  15. Feature: J. Wixon and J. Ashurst, "Genome Informatics," Computational Functional Genomics 4 (5), pp. 509–514 (October 2003).

  16. Citation: K. S. Thorne et al., "Noise in Gravitational-Wave Detectors and Other Classical-Force Measurements is Not Influenced by Test-Mass Quantization," Physical Review D 67 (8), article 082001 (April 2003).

  17. Commentary: L. Y. Dirix and A. T. van Oosterom, "Gene-Expression Profiling to Classify Soft-Tissue Sarcomas," Lancet 359 (9314), pp. 1263–1264 (April 2002).

  18. Mention: 9th most cited Proceedings of the National Academy of Sciences (PNAS) USA paper of the year 2000 and 56th most cited PNAS paper of all time, Google Scholar (August 26, 2022).

  19. Feature: B. H. Ripin, "1998 Outstanding Doctoral Thesis Research in Atomic, Molecular, or Optical Physics (DAMOP) Award Finalists," American Physical Society (APS) News 7 (8), p. 5 (August–September 1998).50