Skip to main content

Advertisement

Log in

Tensor Factorization for Precision Medicine in Heart Failure with Preserved Ejection Fraction

  • Review
  • Published:
Journal of Cardiovascular Translational Research Aims and scope Submit manuscript

Abstract

Heart failure with preserved ejection fraction (HFpEF) is a heterogeneous clinical syndrome that may benefit from improved subtyping in order to better characterize its pathophysiology and to develop novel targeted therapies. The United States Precision Medicine Initiative comes amid the rapid growth in quantity and modality of clinical data for HFpEF patients ranging from deep phenotypic to trans-omic data. Tensor factorization, a form of machine learning, allows for the integration of multiple data modalities to derive clinically relevant HFpEF subtypes that may have significant differences in underlying pathophysiology and differential response to therapies. Tensor factorization also allows for better interpretability by supporting dimensionality reduction and identifying latent groups of data for meaningful summarization of both features and disease outcomes. In this narrative review, we analyze the modest literature on the application of tensor factorization to related biomedical fields including genotyping and phenotyping. Based on the cited work including work of our own, we suggest multiple tensor factorization formulations capable of integrating the deep phenotypic and trans-omic modalities of data for HFpEF, or accounting for interactions between genetic variants at different omic hierarchies. We encourage extensive experimental studies to tackle challenges in applying tensor factorization for precision medicine in HFpEF, including effectively incorporating existing medical knowledge, properly accounting for uncertainty, and efficiently enforcing sparsity for better interpretability.

This is a preview of subscription content, log in via an institution to check access.

Access this article

Price excludes VAT (USA)
Tax calculation will be finalised during checkout.

Instant access to the full article PDF.

Fig. 1
Fig. 2
Fig. 3

Similar content being viewed by others

References

  1. Mozaffarian, D., Benjamin, E.J., Go, A.S., et al. (2015).Heart disease and stroke statistics—2016 update. A Report From the American Heart Association.

  2. Yancy, C. W., Jessup, M., Bozkurt, B., et al. (2013). 2013 ACCF/AHA guideline for the management of heart failure: a report of the American College of Cardiology Foundation/American Heart Association Task Force on Practice Guidelines. Journal of the American College of Cardiology, 62(16), e147–e239.

    Article  PubMed  Google Scholar 

  3. Samson, R., Jaiswal, A., Ennezat, P. V., Cassidy, M., & Le Jemtel, T. H. (2016). Clinical phenotypes in heart failure with preserved ejection fraction. Journal of the American Heart Association., 5(1), e002477.

    Article  PubMed  PubMed Central  Google Scholar 

  4. Shah, S. J., Kitzman, D. W., Borlaug, B. A., et al. (2016). Phenotype-specific treatment of heart failure with preserved ejection fraction. A Multiorgan Roadmap., 134(1), 73–90.

    Google Scholar 

  5. Paulus, W. J., & Tschöpe, C. (2013). A novel paradigm for heart failure with preserved ejection fraction: comorbidities drive myocardial dysfunction and remodeling through coronary microvascular endothelial inflammation. Journal of the American College of Cardiology, 62(4), 263–271.

    Article  PubMed  Google Scholar 

  6. Vaduganathan, M., Michel, A., Hall, K., et al. (2016). Spectrum of epidemiological and clinical findings in patients with heart failure with preserved ejection fraction stratified by study design: a systematic review. European Journal of Heart Failure, 18(1), 54–65.

    Article  PubMed  Google Scholar 

  7. Shah, S.J., Katz, D.H., Selvaraj, S., et al. (2014). Phenomapping for novel classification of heart failure with preserved ejection fraction. Circulation :CIRCULATIONAHA. 114.010637.

  8. Kapuku, G. K., Ge, D., Vemulapalli, S., Harshfield, G. A., Treiber, F. A., & Snieder, H. (2008). Change of genetic determinants of left ventricular structure in adolescence: longitudinal evidence from the Georgia cardiovascular twin study. American Journal of Hypertension, 21(7), 799–805.

    Article  CAS  PubMed  Google Scholar 

  9. Tang, W., Devereux, R. B., Li, N., et al. (2009). Identification of a pleiotropic locus on chromosome 7q for a composite left ventricular wall thickness factor and body mass index: the HyperGEN Study. BMC Medical Genetics, 10(1), 1.

    Article  Google Scholar 

  10. Vasan, R. S., Glazer, N. L., Felix, J. F., et al. (2009). Genetic variants associated with cardiac structure and function: a meta-analysis and replication of genome-wide association data. Journal of the American Medical Association, 302(2), 168–178.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  11. Smith, N. L., Felix, J. F., Morrison, A. C., et al. (2010). Association of genome-wide variation with the risk of incident heart failure in adults of European and African ancestry a prospective meta-analysis from the cohorts for heart and aging research in genomic epidemiology (CHARGE) consortium. Circulation. Cardiovascular Genetics, 3(3), 256–266.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  12. Larson, M. G., Atwood, L. D., Benjamin, E. J., et al. (2007). Framingham Heart Study 100 K project: genome-wide associations for cardiovascular disease outcomes. BMC Medical Genetics, 8(1), 1.

    Google Scholar 

  13. Morrison, A. C., Felix, J. F., Cupples, L. A., et al. (2010). Genomic variation associated with mortality among adults of European and African ancestry with heart failure the cohorts for heart and aging research in genomic epidemiology consortium. Circulation. Cardiovascular Genetics, 3(3), 248–255.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  14. Berezin, A. (2016). Epigenetics in heart failure phenotypes. BBA Clinical., 6, 31–37.

    Article  PubMed  PubMed Central  Google Scholar 

  15. Kohane, I. S. (2015). Ten things we have to do to achieve precision medicine. Science, 349(6243), 37–38.

    Article  CAS  PubMed  Google Scholar 

  16. Bild, D. E., Bluemke, D. A., Burke, G. L., et al. (2002). Multi-ethnic study of atherosclerosis: objectives and design. American Journal of Epidemiology, 156(9), 871–881.

    Article  PubMed  Google Scholar 

  17. Winslow, R. L., Trayanova, N., Geman, D., & Miller, M. I. (2012). Computational medicine: translating models to clinical care. Science Translational Medicine, 4(158), 158rv111–158rv111.

    Article  Google Scholar 

  18. Luo, Y., Uzuner, Ö., Szolovits, P. (2016). Bridging semantics and syntax with graph algorithms—state-of-the-art of extracting biomedical relations. Briefings in Bioinformatics.

  19. Moskovitch, R., & Shahar, Y. (2015). Classification of multivariate time series via temporal abstraction and time intervals mining. Knowledge and Information Systems., 45(1), 35–74.

    Article  Google Scholar 

  20. Lee, D. D., & Seung, H. S. (1999). Learning the parts of objects by non-negative matrix factorization. Nature, 401(6755), 788–791.

    Article  CAS  PubMed  Google Scholar 

  21. Steyvers, M., & Griffiths, T. (2007). Probabilistic topic models. Handbook of latent semantic analysis., 427(7), 424–440.

    Google Scholar 

  22. Luo, Y., Sohani, A. R., Hochberg, E. P., & Szolovits, P. (2014). Automatic lymphoma classification with sentence subgraph mining from pathology reports. Journal of the American Medical Informatics Association, 21(5), 824–832.

    Article  PubMed  PubMed Central  Google Scholar 

  23. Luo, Y., Xin, Y., Hochberg, E., Joshi, R., Uzuner, O., Szolovits, P. (2015). Subgraph augmented non-negative tensor factorization (SANTF) for modeling clinical narrative text. Journal of the American Medical Informatics Association :ocv016.

  24. Luo, Y., Xin, Y., Joshi, R., Celi, L., Szolovits, P. (2016). Predicting ICU mortality risk by grouping temporal trends from a multivariate panel of physiologic measurements.

  25. Kolda, T. G., & Bader, B. W. (2009). Tensor decompositions and applications. SIAM review., 51(3), 455–500.

    Article  Google Scholar 

  26. Cichocki, A. (2014). Tensor networks for big data analytics and large-scale optimization problems. arXiv preprint arXiv :14073124.

  27. Han, D., Wang, S., Jiang, C., et al. (2015). Trends in biomedical informatics: automated topic analysis of <em>JAMIA</em> articles. Journal of the American Medical Informatics Association, 22(6), 1153–1163.

    Article  PubMed  PubMed Central  Google Scholar 

  28. Wang, Y., Chen, R., Ghosh, J., et al. (2015). Rubik: knowledge guided tensor factorization and completion for health data analytics. Paper presented at: Proceedings of the 21th ACM SIGKDD International Conference on Knowledge Discovery and Data Mining.

  29. Tucker, L. R. (1966). Some mathematical notes on three-mode factor analysis. Psychometrika, 31(3), 279–311.

    Article  CAS  PubMed  Google Scholar 

  30. Carroll, J. D., & Chang, J.-J. (1970). Analysis of individual differences in multidimensional scaling via an N-way generalization of “Eckart-Young” decomposition. Psychometrika, 35(3), 283–319.

    Article  Google Scholar 

  31. Mørup, M. (2011). Applications of tensor (multiway array) factorizations and decompositions in data mining. Wiley Interdisciplinary Reviews: Data Mining and Knowledge Discovery., 1(1), 24–40.

    Google Scholar 

  32. Vogelstein, B., Papadopoulos, N., Velculescu, V. E., Zhou, S., Diaz, L. A., & Kinzler, K. W. (2013). Cancer genome landscapes. Science, 339(6127), 1546–1558.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  33. Nik-Zainal, S., Alexandrov, L. B., Wedge, D. C., et al. (2012). Mutational processes molding the genomes of 21 breast cancers. Cell, 149(5), 979–993.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  34. Franceschini, A., Szklarczyk, D., Frankild, S., et al. (2013). STRING v9. 1: protein-protein interaction networks, with increased coverage and integration. Nucleic Acids Research, 41(D1), D808–D815.

    Article  CAS  PubMed  Google Scholar 

  35. Kanehisa, M., Goto, S., Sato, Y., Furumichi, M., Tanabe, M. (2011). KEGG for integration and interpretation of large-scale molecular data sets. Nucleic Acids Research :gkr988.

  36. Hunter, S., Jones, P., Mitchell, A., et al. (2011). InterPro in 2011: new developments in the family and domain prediction database. Nucleic Acids Research :gkr948.

  37. Thierry-Mieg, D., & Thierry-Mieg, J. (2006). AceView: a comprehensive cDNA-supported gene and transcripts annotation. Genome Biology, 7(1), 1.

    Article  PubMed  Google Scholar 

  38. Finn, R.D., Bateman, A., Clements, J., et al. (2013). Pfam: the protein families database. Nucleic Acids Research :gkt1223.

  39. Luo, Y., & Szolovits, P. (2016). Efficient queries of stand-off annotations for natural language processing on electronic medical records. Biomedical Informatics Insights., 8, 29–38.

    Article  PubMed  PubMed Central  Google Scholar 

  40. Luo, Y., Wang, F., Szolovits, P. (2016). Tensor factorization toward precision medicine. Briefings in Bioinformatics.

  41. Cong, F., Lin, Q.-H., Kuang, L.-D., Gong, X.-F., Astikainen, P., & Ristaniemi, T. (2015). Tensor decomposition of EEG signals: a brief review. Journal of Neuroscience Methods, 248, 59–69.

    Article  PubMed  Google Scholar 

  42. Ho, J. C., Ghosh, J., Steinhubl, S. R., et al. (2014). Limestone: high-throughput candidate phenotype generation via tensor factorization. Journal of biomedical informatics., 52, 199–211.

    Article  PubMed  Google Scholar 

  43. Ho, J.C., Ghosh, J., Sun, J. (2014). Marble: high-throughput phenotyping from electronic health records via sparse nonnegative tensor factorization. Paper presented at: Proceedings of the 20th ACM SIGKDD international conference on Knowledge discovery and data mining.

  44. Wang, F., Zhang, P., Qian, B., Wang, X., Davidson, I. (2014). Clinical risk prediction with multilinear sparse logistic regression. Paper presented at: Proceedings of the 20th ACM SIGKDD international conference on Knowledge discovery and data mining.

  45. Kessler, D.C., Taylor, J., Dunson, D.B. (2014). Learning phenotype densities conditional on many interacting predictors. Bioinformatics :btu040.

  46. Yang, Y., Dunson, D.B. (2015). Bayesian conditional tensor factorizations for high-dimensional classification. Journal of the American Statistical Association. (just-accepted).

  47. Zhou, J., Bhattacharya, A., Herring, A. H., & Dunson, D. B. (2015). Bayesian factorizations of big sparse tensors. Journal of the American Statistical Association., 110(512), 1562–1576.

    Article  CAS  Google Scholar 

  48. Rai P, Wang Y, Guo S, Chen G, Dunson DB, Carin L. (2014). Scalable Bayesian low-rank decomposition of incomplete multiway tensors. Paper presented at: ICML.

  49. Mørup, M., Hansen, L. K., & Arnfred, S. M. (2008). Algorithms for sparse nonnegative Tucker decompositions. Neural Computation, 20(8), 2112–2131.

    Article  PubMed  Google Scholar 

  50. Sun, W., Lu, J., Liu, H., Cheng, G. (2015). Provable sparse tensor decomposition. arXiv preprint arXiv :150201425.

Download references

Acknowledgements

Dr. Ahmad is supported by the National Heart, Lung, and Blood Institute of the National Institutes of Health (NIH) under Award number T32HL069771. Dr. Shah is supported by the NIH R01 HL107577 and R01 HL127028 and American Heart Association grants #15CVGPSD27260148 and #16SFRN28780016.

Author information

Authors and Affiliations

Authors

Corresponding author

Correspondence to Yuan Luo.

Additional information

Associate Editor Daniel P. Judge oversaw the review of this article

Rights and permissions

Reprints and permissions

About this article

Check for updates. Verify currency and authenticity via CrossMark

Cite this article

Luo, Y., Ahmad, F.S. & Shah, S.J. Tensor Factorization for Precision Medicine in Heart Failure with Preserved Ejection Fraction. J. of Cardiovasc. Trans. Res. 10, 305–312 (2017). https://doi.org/10.1007/s12265-016-9727-8

Download citation

  • Received:

  • Accepted:

  • Published:

  • Issue Date:

  • DOI: https://doi.org/10.1007/s12265-016-9727-8

Keywords

Navigation