Cited by 77Gene expression and cancer classificationMachine Learning in HealthcareBreast Cancer Treatment Studies

Improved survival analysis by learning shared genomic information from pan-cancer data

Open access
Kim, Sunkyu, Kim, Keonwoo, Choe, Junseok, Lee, Inggeol, Kang, Jaewoo·2020·Bioinformatics

Abstract

Motivation: Recent advances in deep learning have offered solutions to many biomedical tasks. However, there remains a challenge in applying deep learning to survival analysis using human cancer transcriptome data. As the number of genes, the input variables of survival model, is larger than the amount of available cancer patient samples, deep-learning models are prone to overfitting. To address the issue, we introduce a new deep-learning architecture called VAECox. VAECox uses transfer learning and fine tuning. Results: We pre-trained a variational autoencoder on all RNA-seq data in 20 TCGA datasets and transferred the trained weights to our survival prediction model. Then we fine-tuned the transferred weights during training the survival model on each dataset. Results show that our model outperformed other previous models such as Cox Proportional Hazard with LASSO and ridge penalty and Cox-nnet on the 7 of 10 TCGA datasets in terms of C-index. The results signify that the transferred information obtained from entire cancer transcriptome data helped our survival prediction model reduce overfitting and show robust performance in unseen cancer patient samples. Availability and implementation: Our implementation of VAECox is available at https://github.com/dmis-lab/VAECox. Supplementary information: Supplementary data are available at Bioinformatics online.

The claims and statistics of this paper haven’t been checked yet.

Run the check — free, no account needed. It reads the open-access text and checks the sources it cites.

A few free checks a day · papers already verified open instantly · results are public

Integrity signals

Registry

Crossref · 10.1093/bioinformatics/btaa462

Cites

Statistics

Claims the paper makes

The claims and statistics of this paper haven’t been checked yet.

Run the check — free, no account needed. It reads the open-access text and checks the sources it cites.

A few free checks a day · papers already verified open instantly · results are public

Claims other papers make about this one

Each is checked against this paper’s own text: does it say what the citing paper says it does?

  • The pretrain-and-finetune framework has shown effectiveness in computer vision learning, neural language processing, and biomedical learning for prognosis prediction and cancer dependency prediction.

    “The pretrain-and-finetune framework has shown its effectiveness in computer vision learning, neural language processing, and biomedical learning for prognosis prediction [179] and cancer dependency prediction [180].”

Self-check

Percentages, sums and reported differences re-computed from the paper’s own numbers.

The self-check needs the paper’s full text.

The citation lists haven’t been fetched yet

References 51 · Cited by 77

Research works printed but not linked: 43

  1. Bon E. et al (2016) SCN4B acts as a metastasis-suppressor gene preventing hyperactivation of cell migration in breast cancer. Nat. Commun., 7, 1– 18. PMC5150224 27917859
  2. Chaudhary K. et al (2018) Deep learning-based multi-omics integration robustly predicts survival in liver cancer. Clin. Cancer Res., 24, 1248– 1259. 28982688 PMC6050171
  3. Ching T. et al (2018) Cox-nnet: an artificial neural network method for prognosis prediction of high-throughput omics data. PLoS Comput. Biol., 14, e1006076. 29634719 PMC5909924
  4. Cho M.-H. et al (2015) DOT1L cooperates with the c-Myc-p300 complex to epigenetically derepress CDH1 transcription factors in breast cancer progression. Nat. Commun., 6, 1– 14. PMC4525167 26199140
  5. Cox D.R. (2018) Analysis of Survival Data. Routledge, England, UK.
  6. de Oca R.M. et al (2015) The histone chaperone HJURP is a new independent prognostic marker for luminal a breast carcinoma. Mol. Oncol., 9, 657– 674. 25497280 PMC5528705
  7. Dewa C.K. et al (2018) Suitable CNN weight initialization and activation function for Javanese vowels classification. Proc. Comput. Sci., 144, 124– 132.
  8. Dimitrakopoulos C. et al (2018) Network-based integration of multi-omics data for prioritizing cancer genes. Bioinformatics, 34, 2441– 2448. 29547932 PMC6041755
  9. Doersch C. (2016) Tutorial on variational autoencoders. CoRR, abs/1606.05908, http://arxiv.org/abs/1606.05908. · arXiv
  10. Fernandes K. et al (2017) Transfer learning with partial observability applied to cervical cancer screening. In: Iberian Conference on Pattern Recognition and Image Analysis, pp. 243– 250. Springer, NY, US.
  11. Fu W. et al (2019) BCAP31 drives TNBC development by modulating ligand-independent EGFR trafficking and spontaneous EGFR phosphorylation. Theranostics, 9, 6468– 6484. 31588230 PMC6771250
  12. Hanahan D., Weinberg R.A. (2011) Hallmarks of cancer: the next generation. Cell, 144, 646– 674. 21376230
  13. Hanin B., Rolnick D. (2018) How to start training: the effect of initialization and architecture. In: Advances in Neural Information Processing Systems, Neural Information Processing Systems Foundation, La Jolla, CA, pp. 571– 581.
  14. Harrell F.E. Jr, (2015) Regression Modeling Strategies: With Applications to Linear Models, Logistic and Ordinal Regression, and Survival Analysis. Springer, NY, US.
  15. Hinton G.E., Salakhutdinov R.R. (2006) Reducing the dimensionality of data with neural networks. Science, 313, 504– 507. 16873662
  16. Hu Z. et al (2010) The expression level of HJURP has an independent prognostic impact and predicts the sensitivity to radiotherapy in breast cancer. Breast Cancer Res., 12, R18. 20211017 PMC2879562
  17. Huang C.-J. et al (2011) A predicted protein, KIAA0247, is a cell cycle modulator in colorectal cancer cells under 5-FU treatment. J. Transl. Med., 9, 82. 21619678 PMC3126726
  18. Huang L. et al (2019a) Driver network as a biomarker: systematic integration and network modeling of multi-omics data to derive driver signaling pathways for drug combination prediction. Bioinformatics, 35, 3709– 3717. 30768150 PMC6761967
  19. Jiang J. et al (2011) Ganodermanontriol (GDNT) exerts its effect on growth and invasiveness of breast cancer cells through the down-regulation of CDC20 and uPA. Biochem. Biophys. Res. Commun., 415, 325– 329. 22033405
  20. Kandaswamy C. et al (2016) High-content analysis of breast cancer using single-cell deep transfer learning. J. Biomol. Screen., 21, 252– 259. 26746583
  21. Karra H. et al (2014) Cdc20 and securin overexpression predict short-term breast cancer survival. Br. J. Cancer, 110, 2905– 2913. 24853182 PMC4056061
  22. Kingma D.P., Welling M. (2013) Auto-encoding variational Bayes. CoRR, abs/1312.6114, http://arxiv.org/1312.6114. · arXiv
  23. Lee J.-Y., Kong G. (2015) Dot1l: a new therapeutic target for aggressive breast cancer. Oncotarget, 6, 30451– 30452. 26427043 PMC4741543
  24. Lerebours F. et al (2008) NF-kappa B genes have a major role in inflammatory breast cancer. BMC Cancer, 8, 41. 18248671 PMC2267801
  25. Li Y.-Y. et al (2013) Down-regulation of C9orf86 in human breast cancer cells inhibits cell proliferation, invasion and tumor growth and correlates with survival of breast cancer patients. PLoS One, 8, e71764. 23977139 PMC3743754
  26. Li Y. et al (2016) Transfer learning for survival analysis via efficient l2, 1-norm regularized cox regression. In: 2016 IEEE 16th International Conference on Data Mining (ICDM), pp. 231– 240. IEEE, Piscataway, New Jersey, US.
  27. Li S. et al (2017) Initializing convolutional filters with semantic features for text classification. In Proceedings of the 2017 Conference on Empirical Methods in Natural Language Processing, pp. 1884– 1889.
  28. Lussier Y.A., Li H. (2012) Breakthroughs in genomics data integration for predicting clinical outcome. J. Biomed. Inf., 45, 1199– 1201. PMC3632294 23117078
  29. Mannelqvist M. et al (2014) An 18-gene signature for vascular invasion is associated with aggressive features and reduced survival in breast cancer. PLoS One, 9, e98787. 24905342 PMC4048217
  30. Meng L. et al (2016) Biomarker discovery to improve prediction of breast cancer survival: using gene expression profiling, meta-analysis, and tissue validation. OncoTargets Ther., 9, 6177– 6185. PMC5067006 27785066
  31. Nassa G. et al (2019) Inhibition of histone methyltransferase DOT1L silences ERα gene and blocks proliferation of antiestrogen-resistant breast cancer cells. Sci. Adv., 5, eaav5590. 30775443 PMC6365116
  32. Nicholson R. et al (2001) EGFR and cancer prognosis. Eur. J. Cancer, 37, 9– 15. 11597399
  33. Pan S.J., Yang Q. (2010) A survey on transfer learning. IEEE Trans. Knowl. Data Eng., 22, 1345– 1359.
  34. Polato F. et al (2014) DRAGO (KIAA0247), a new DNA damage–responsive, p53-inducible gene that cooperates with p53 as oncosuppressor. JNCI J. Natl. Cancer Inst., 106, 4. PMC3988459 24652652
  35. Press W.H. et al (2007) Numerical Recipes 3rd Edition: The Art of Scientific Computing. Cambridge University Press, Cambridge, England.
  36. Rendle S. (2012) Factorization machines with libFM. ACM Trans. Intell. Syst. Technol., 3, 1– 22.
  37. Sutskever I. et al (2013) On the importance of initialization and momentum in deep learning. In: International Conference on Machine Learning, ACM, NY, pp. 1139– 1147.
  38. Titus A.J. et al (2017) Deconvolution of DNA methylation identifies differentially methylated gene regions on 1p36 across breast cancer subtypes. Sci. Rep., 7, 1– 9. 28912426 PMC5599639
  39. Tomczak K. et al (2015) The cancer genome atlas (TCGA): an immeasurable source of knowledge. Contemp. Oncol., 1A, 68– 77. PMC4322527 25691825
  40. Valdes Mora F. et al (2018) Single-cell transcriptomics in cancer immunobiology: the future of precision oncology. Front. Immunol., 9, 2582. 30483257 PMC6240655
  41. Van’t Veer L.J. et al (2002) Gene expression profiling predicts clinical outcome of breast cancer. Nature, 415, 530– 536. 11823860
  42. Venter J.C. et al (2001) The sequence of the human genome. Science, 291, 1304– 1351. 11181995
  43. Yoshimura K. et al (2016) A novel prognostic marker of non-small cell lung cancer: chromosome 9 open reading frame 86 (C9orf86). J. Thoracic Dis., 8, 2284– 2286. PMC5059359 27746955

Authors
Kim, S., Kim, K., Choe, J., Lee, I., & Kang, J.
Affiliations
Korea University (KR)
Corresponding author
Kang, Jaewoo
Venue
Bioinformatics
Published
2020-07-01
Volume
36
Issue
Supplement_1
Pages
i389-i398
ISSN
  • 1367-4803 (ISSN-L)
  • 1367-4811
OpenAlex
W3043242675
Cited by
77
References
51
Citations by year
2026: 4 · 2025: 21 · 2024: 15 · 2023: 15 · 2022: 13 · 2021: 8 · 2020: 1
FWCI
3.00
Type
journal article
Language
en
Open access
Locations
  • Bioinformatics (publishedVersion, cc-by-nc)
  • PubMed Central (publishedVersion, cc-by-nc)
  • PubMed (publishedVersion)
Funders
National Research Foundation of Korea (NRF-2017R1A2A1A17069645, NRF-2016M3A9A7916996, NRF-2014M3C9A3063541)
Topics
  • Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Gene expression and cancer classification
  • Physical Sciences › Computer Science › Artificial Intelligence › Machine Learning in Healthcare
  • Life Sciences › Biochemistry, Genetics and Molecular Biology › Cancer Research › Breast Cancer Treatment Studies
Keywords
survival analysis, pan-cancer, variational autoencoder, transfer learning, fine-tuning, RNA-seq, tumor transcriptome, overfitting, TCGA, Cox proportional hazards model, survival prediction
MeSH terms
Deep Learning, Humans, Neoplasms, Survival Analysis, Genome, Genomics

About these checks

Registry, retraction, Cites and statistics results are computed, not judged, with one exception: a printed reference that no index lists is read once by a model before it counts as a citation error. Claims are extracted by a model and kept only when their quote appears verbatim in the text; each cited source is then checked, with a model’s help, for whether it says what the claim relies on. Those verdicts can be wrong — read the claim’s quote and the cited source before relying on one.

Statistics and arithmetic are recomputed, not judged.

Confidence bands are shown only for fields calibrated on our annotated test set. None is calibrated yet, so no band is shown.

What counts as a claim ›How we measure confidence ›How we check this ›

Are you an author, or do you see a problem with this page? Request a review