Shen LiTo study the molecular mechanisms of drug addiction and depression, a lot of high throughput experimental data have been generated. Our lab focuses on the statistical and integrated analysis of these data and generates biological insights. We are especially interested in the next-generation sequencing data which provides a comprehensive and high-resolution view of the biological systems under study. We also develop bioinformatic tools employing Bayesian inference and machine learning to aid our data analysis.

Contact Us

Shen Laboratory
Li Shen, PhD
Professor, Neuroscience
Lab: ICAHN 10-26
Office: ICAHN 10
Office: 212.659.8622

Machine Learning



  • Detecting differential chromatin modification sites from ChIP-seq data with biological replicates – diffReps
  • An easy-to-use visualization tool for global enrichment of next-generation sequencing data – ngs.plot


  1. Bagot, R.C., Cates, H.M., Purushothaman, I., Vialou, V., Heller, E.A., Yieh, L., LaBonté, B., Peña, C.J., Shen, L., Wittenberg, G.M., et al. (2017). Ketamine and Imipramine Reverse Transcriptional Signatures of Susceptibility and Induce Resilience-Specific Gene Expression Profiles. Biological Psychiatry 81, 285–295.
  2. Descalzi, G., Mitsi, V., Purushothaman, I., Gaspari, S., Avrampou, K., Loh, Y.-H.E., Shen, L., and Zachariou, V. (2017). Neuropathic pain promotes adaptive changes in gene expression in brain networks involved in stress and depression. Sci. Signal. 10, eaaj1549.
  3. Engmann, O., Labonté, B., Mitchell, A., Bashtrykov, P., Calipari, E.S., Rosenbluh, C., Loh, Y.-H.E., Walker, D.M., Burek, D., Hamilton, P.J., et al. (2017). Cocaine-Induced Chromatin Modifications Associate With Increased Expression and Three-Dimensional Looping of Auts2. Biological Psychiatry.
  4. Feng, J., Pena, C.J., Purushothaman, I., Engmann, O., Walker, D., Brown, A.N., Issler, O., Doyle, M., Harrigan, E., Mouzon, E., et al. (2017). Tet1 in Nucleus Accumbens Opposes Depression- and Anxiety-Like Behaviors. Neuropsychopharmacology.
  5. Jiang, Y., Loh, Y.-H.E., Rajarajan, P., Hirayama, T., Liao, W., Kassim, B.S., Javidfar, B., Hartley, B.J., Kleofas, L., Park, R.B., et al. (2017). The methyltransferase SETDB1 regulates a large neuron-specific topological chromatin domain. Nat Genet advance online publication.
  6. Loh, Y.-H.E., Koemeter-Cox, A., Finelli, M.J., Shen, L., Friedel, R.H., and Zou, H. (2017a). Comprehensive mapping of 5-hydroxymethylcytosine epigenetic dynamics in axon regeneration. Epigenetics 12, 77–92.
  7. Loh, Y.-H.E., Feng, J., Nestler, E., and Shen, L. (2017b). Bioinformatic Analysis for Profiling Drug-induced Chromatin Modification  Landscapes in Mouse Brain Using ChlP-seq Data. Bio-Protocol 7, e2123.
  8. Peña, C.J., Kronman, H.G., Walker, D.M., Cates, H.M., Bagot, R.C., Purushothaman, I., Issler, O., Loh, Y.-H.E., Leong, T., Kiraly, D.D., et al. (2017). Early life stress confers lifelong stress susceptibility in mice via ventral tegmental area OTX2. Science 356, 1185–1188.
  9. Shen, L. (2017a). End-to-end Training for Whole Image Breast Cancer Diagnosis using An All Convolutional Design. ArXiv:1708.09427 [Cs, Stat].
  10. Shen, L. (2017b). Breast cancer diagnosis using deep residual nets and transfer learning.
  11. Wan, L., Wen, H., Li, Y., Lyu, J., Xi, Y., Hoshii, T., Joseph, J.K., Wang, X., Loh, Y.-H.E., Erb, M.A., et al. (2017). ENL links histone acetylation to oncogenic gene expression in acute myeloid leukaemia. Nature 543, 265–269.
  1. Bagot, R.C., Cates, H.M., Purushothaman, I., Lorsch, Z.S., Walker, D.M., Wang, J., Huang, X., Schluter, O.M., Maze, I., Pena, C.J., et al. (2016). Circuit-wide Transcriptional Profiling Reveals Brain Region-Specific Gene Networks Regulating Depression Susceptibility. Neuron 90, 969–983.
  2. Cahill, M.E., Bagot, R.C., Gancarz, A.M., Walker, D.M., Sun, H., Wang, Z.-J., Heller, E.A., Feng, J., Kennedy, P.J., Koo, J.W., et al. (2016). Bidirectional Synaptic Structural Plasticity after Chronic Cocaine Administration Occurs through Rap1 Small GTPase Signaling. Neuron 89, 566–582.
  3. Damez-Werno, D.M., Sun, H., Scobie, K.N., Shao, N., Rabkin, J., Dias, C., Calipari, E.S., Maze, I., Pena, C.J., Walker, D.M., et al. (2016). Histone arginine methylation in cocaine action in the nucleus accumbens. PNAS 113, 9623–9628.
  4. Lepack, A.E., Bagot, R.C., Peña, C.J., Loh, Y.-H.E., Farrelly, L.A., Lu, Y., Powell, S.K., Lorsch, Z.S., Issler, O., Cates, H.M., et al. (2016). Aberrant H3.3 dynamics in NAc promote vulnerability to depressive-like behavior. PNAS 113, 12562–12567.
  5. Loh, Y.-H.E., Koemeter-Cox, A., Finelli, M.J., Shen, L., Friedel, R.H., and Zou, H. (2016). Comprehensive mapping of 5-hydroxymethylcytosine epigenetic dynamics in axon regeneration. Epigenetics 0, 1–16.
  6. Pfau, M.L., Purushothaman, I., Feng, J., Golden, S.A., Aleyasin, H., Lorsch, Z.S., Cates, H.M., Flanigan, M.E., Menard, C., Heshmati, M., et al. (2016). Integrative Analysis of Sex-Specific microRNA Networks Following Stress in Mouse Nucleus Accumbens. Front. Mol. Neurosci. 9.
  7. Shen, E.Y., Jiang, Y., Javidfar, B., Kassim, B., Loh, Y.-H.E., Ma, Q., Mitchell, A.C., Pothula, V., Stewart, A.F., Ernst, P., et al. (2016). Neuronal Deletion of Kmt2a/Mll1 Histone Methyltransferase in Ventral Striatum is Associated with Defective Spike-Timing-Dependent Striatal Synaptic Plasticity, Altered Response to Dopaminergic Drugs, and Increased Anxiety. Neuropsychopharmacology 41, 3103–3113.
  8. Sun, H., Martin, J.A., Werner, C.T., Wang, Z.-J., Damez-Werno, D.M., Scobie, K.N., Shao, N.-Y., Dias, C., Rabkin, J., Koo, J.W., et al. (2016). BAZ1B in Nucleus Accumbens Regulates Reward-Related Behaviors in Response to Distinct Emotional Stimuli. The Journal of Neuroscience 36, 3954–3961.
  9. Wang, T., Santos, J.H., Feng, J., Fargo, D.C., Shen, L., Riadi, G., Keeley, E., Rosh, Z.S., Nestler, E.J., and Woychik, R.P. (2016). A Novel Analytical Strategy to Identify Fusion Transcripts between Repetitive Elements and Protein Coding-Exons Using RNA-Seq. PLoS ONE 11, e0159028.
  10. Yong-Hwee Eddie Loh, and Shen, L. (2016). Analysis and Visualization of ChIP-Seq and RNA-Seq Sequence Alignments Using ngs.plot. In Data Mining Techniques for the Life Sciences, O. Carugo, and F. Eisenhaber, eds. (New York, NY: Springer New York), pp. 371–383.

Shen, L. (2015) Automatic genome segmentation with HMM-ANN hybrid models. Workshops on Machine Learning in Computational Biology at the Annual Conference on Neural Information Processing Systems (NIPS). bioRxiv,

Sun, H., Damez-Werno, D.M., Scobie, K.N., Shao, N.Y., Dias, C., Rabkin, J., Koo, J.W., Korb, E., Bagot, R.C., Ahn, F.H., Cahill, M.E., Labonte, B., Mouzon, E., Heller, E.A., Cates, H., Golden, S.A., Gleason, K., Russo, S.J., Andrews, S., Neve, R., Kennedy, P.J., Maze, I., Dietz, D.M., Allis, C.D., Turecki, G., Varga-Weisz, P., Tamminga, C., Shen, L. and Nestler, E.J. (2015) ACF chromatin-remodeling complex mediates stress-induced depressive-like behavior, Nat Med, 21, 1146-1153.

Mitsi, V., Terzi, D., Purushothaman, I., Manouras, L., Gaspari, S., Neve, R.L., Stratinaki, M., Feng, J., Shen, L. and Zachariou, V. (2015) RGS9-2–controlled adaptations in the striatum determine the onset of action and efficacy of antidepressants in neuropathic pain states, Proceedings of the National Academy of Sciences, 112, E5088-E5097.

Ferguson, D., Shao, N., Heller, E., Feng, J., Neve, R., Kim, H.-D., Call, T., Magazu, S., Shen, L. and Nestler, E.J. (2015) SIRT1-FOXO3a Regulate Cocaine Actions in the Nucleus Accumbens, The Journal of Neuroscience, 35, 3100-3111.

Ding, J., Huang, X., Shao, N., Zhou, H., Lee, D.F., Faiola, F., Fidalgo, M., Guallar, D., Saunders, A., Shliaha, P.V., Wang, H., Waghray, A., Papatsenko, D., Sanchez-Priego, C., Li, D., Yuan, Y., Lemischka, I.R., Shen, L., Kelley, K., Deng, H., Shen, X. and Wang, J. (2015) Tex10 Coordinates Epigenetic Control of Super-Enhancer Activity in Pluripotency and Reprogramming, Cell Stem Cell, 16, 653-668.

Feng, J., Shao, N., Szulwach, K.E., Vialou, V., Huynh, J., Zhong, C., Le, T., Ferguson, D., Cahill, M.E., Li, Y., Koo, J.W., Ribeiro, E., Labonte, B., Laitman, B.M., Estey, D., Stockman, V., Kennedy, P., Courousse, T., Mensah, I., Turecki, G., Faull, K.F., Ming, G.-l., Song, H., Fan, G., Casaccia, P., Shen, L., Jin, P. and Nestler, E.J. (2015) Role of Tet1 and 5-hydroxymethylcytosine in cocaine action, Nat Neurosci, 18, 536-544.

Hodes, G.E., Pfau, M.L., Purushothaman, I., Ahn, H.F., Golden, S.A., Christoffel, D.J., Magida, J., Brancato, A., Takahashi, A., Flanigan, M.E., Ménard, C., Aleyasin, H., Koo, J.W., Lorsch, Z.S., Feng, J., Heshmati, M., Wang, M., Turecki, G., Neve, R., Zhang, B., Shen, L., Nestler, E.J. and Russo, S.J. (2015) Sex Differences in Nucleus Accumbens Transcriptome Profiles Associated with Susceptibility versus Resilience to Subchronic Variable Stress, The Journal of Neuroscience, 35, 16362-16376.

Maze, I., Wenderski, W., Noh, K.-M., Bagot, Rosemary C., Tzavaras, N., Purushothaman, I., Elsässer, Simon J., Guo, Y., Ionete, C., Hurd, Yasmin L., Tamminga, Carol A., Halene, T., Farrelly, L., Soshnev, Alexey A., Wen, D., Rafii, S., Birtwistle, Marc R., Akbarian, S., Buchholz, Bruce A., Blitzer, Robert D., Nestler, Eric J., Yuan, Z.-F., Garcia, Benjamin A., Shen, L., Molina, H. and Allis, C.D. (2015) Critical Role of Histone Turnover in Neuronal Transcription and Plasticity, Neuron, 87, 77-94.

Noh, K.M., Maze, I., Zhao, D., Xiang, B., Wenderski, W., Lewis, P.W., Shen, L., Li, H. and Allis, C.D. (2015) ATRX tolerates activity-dependent histone H3 methyl/phos switching to maintain repetitive element silencing in neurons, Proc Natl Acad Sci U S A, 112, 6820-6827.

Roadmap Epigenomics, Consortium (2015) Integrative analysis of 111 reference human epigenomes, Nature, 518, 317-330.


Dias, C., Feng, J., Sun, H., Shao, N.y., Mazei-Robison, M.S., Damez-Werno, D., Scobie, K., Bagot, R., LaBonte, B., Ribeiro, E., Liu, X., Kennedy, P., Vialou, V., Ferguson, D., Pena, C., Calipari, E.S., Koo, J.W., Mouzon, E., Ghose, S., Tamminga, C., Neve, R., Shen, L. and Nestler, E.J. (2014) [bgr]-catenin mediates stress resilience through Dicer1/microRNA regulation, Nature, advance online publication.

Heller, E.A., Cates, H.M., Pena, C.J., Sun, H., Shao, N., Feng, J., Golden, S.A., Herman, J.P., Walsh, J.J., Mazei-Robison, M., Ferguson, D., Knight, S., Gerber, M.A., Nievera, C., Han, M.H., Russo, S.J., Tamminga, C.S., Neve, R.L., Shen, L., Zhang, H.S., Zhang, F. and Nestler, E.J. (2014) Locus-specific epigenetic remodeling controls addiction- and depression-related behaviors, Nat Neurosci, 17, 1720-1727.

Maze, I., Shen, L., Zhang, B., Garcia, B.A., Shao, N., Mitchell, A., Sun, H., Akbarian, S., Allis, C.D. and Nestler, E.J. (2014) Analytical tools and current challenges in the modern era of neuroepigenomics, Nat Neurosci, 17, 1476-1490.

Feng, J., Wilkinson, M., Liu, X., Purushothaman, I., Ferguson, D., Vialou, V., Maze, I., Shao, N., Kennedy, P., Koo, J., Dias, C., Laitman, B., Stockman, V., LaPlant, Q., Cahill, M., Nestler, E. and Shen, L. (2014) Chronic cocaine-regulated epigenomic changes in mouse nucleus accumbens, Genome Biology, 15, R65.

Shen, L., Shao, N., Liu, X. and Nestler, E. (2014) ngs.plot: Quick mining and visualization of next-generation sequencing data by integrating genomic databases, BMC Genomics, 15, 284.

Scobie, K.N., Damez-Werno, D., Sun, H., Shao, N., Gancarz, A., Panganiban, C.H., Dias, C., Koo, J., Caiafa, P., Kaufman, L., Neve, R.L., Dietz, D.M., Shen, L. and Nestler, E.J. (2014) Essential role of poly(ADP-ribosyl)ation in cocaine action, Proceedings of the National Academy of Sciences, 111, 2005-2010.

Maze, I., Chaudhury, D., Dietz, D.M., Von Schimmelmann, M., Kennedy, P.J., Lobo, M.K., Sillivan, S.E., Miller, M.L., Bagot, R.C., Sun, H., Turecki, G., Neve, R.L., Hurd, Y.L., Shen, L., Han, M.H., Schaefer, A. and N

  1. Ferguson, D., Koo, J.W., Feng, J., Heller, E., Rabkin, J., Heshmati, M., Renthal, W., Neve, R., Liu, X., Shao, N., et al. (2013). Essential Role of SIRT1 Signaling in the Nucleus Accumbens in Cocaine and Morphine Action. The Journal of Neuroscience 33, 16088–16098.
  2. Shen, L., Shao, N.-Y., Liu, X., Maze, I., Feng, J., and Nestler, E.J. (2013a). diffReps: Detecting Differential Chromatin Modification Sites from ChIP-seq Data with Biological Replicates. PLoS ONE 8, e65598.
  3. Shen, L., Choi, I., Nestler, E.J., and Won, K.-J. (2013b). Human Transcriptome and Chromatin Modifications: An ENCODE Perspective. Genomics Inform 11, 60–67.
  4. Wang, T., Liu, J., Shen, L., Tonti-Filippini, J., Zhu, Y., Jia, H., Lister, R., Whitaker, J.W., Ecker, J.R., Millar, A.H., et al. (2013). STAR: an integrated solution to management and visualization of sequencing data. Bioinformatics 29, 3204–3210.
  5. Warren, B.L., Vialou, V.F., Iñiguez, S.D., Alcantara, L.F., Wright, K.N., Feng, J., Kennedy, P.J., LaPlant, Q., Shen, L., Nestler, E.J., et al. (2013). Neurobiological Sequelae of Witnessing Stressful Events in Adult Mice. Biological Psychiatry 73, 7–14.
  1. Kurita, M., Holloway, T., Garcia-Bea, A., Kozlenkov, A., Friedman, A.K., Moreno, J.L., Heshmati, M., Golden, S.A., Kennedy, P.J., Takahashi, N., et al. (2012). HDAC2 regulates atypical antipsychotic responses through the modulation of mGlu2 promoter activity. Nature Neuroscience 15, 1245–1254.
  2. Maze, I., Feng, J., Wilkinson, M.B., Sun, H., Shen, L., and Nestler, E.J. (2011). Cocaine dynamically regulates heterochromatin and repetitive element unsilencing in nucleus accumbens. Proceedings of the National Academy of Sciences 108, 3035–3040.
  3. Sun, H., Maze, I., Dietz, D.M., Scobie, K.N., Kennedy, P.J., Damez-Werno, D., Neve, R.L., Zachariou, V., Shen, L., and Nestler, E.J. (2012). Morphine Epigenomically Regulates Behavior through Alterations in Histone H3 Lysine 9 Dimethylation in the Nucleus Accumbens. The Journal of Neuroscience 32, 17454–17464.
  1. Hawkins, R.D., Hon, G.C., Lee, L.K., Ngo, Q., Lister, R., Pelizzola, M., Edsall, L.E., Kuan, S., Luu, Y., Klugman, S., et al. (2010). Distinct Epigenomic Landscapes of Pluripotent and Lineage-Committed Human Cells. Cell Stem Cell 6, 479–491.
  2. Shen, L., Liu, J., and Wang, W. (2008). GBNet: Deciphering regulatory rules in the co-regulated genes using a Gibbs sampler enhanced Bayesian network approach. BMC Bioinformatics 9, 395.
  3. Shen, L., Chepelev, I., Liu, J., and Wang, W. (2010). Prediction of quantitative phenotypes based on genetic networks: a case study in yeast sporulation. BMC Systems Biology 4, 128.
  4. Won, K.-J., Agarwal, S., Shen, L., Shoemaker, R., Ren, B., and Wang, W. (2009). An Integrated Approach to Identifying Cis-Regulatory Modules in the Human Genome. PLoS ONE 4, e5501.
  1. Shen, L., and Tan, E.C. (2004). Gene Selection for Cancer Classification from Microarray Data using PLS-RLSC. pp. 73–76.
  2. Shen, L., and Tan, E.C. (2005a). PLS and SVD Based Penalized Logistic Regression for Cancer Classification Using Microarray Data. (Imperial College Press), pp. 219–228.
  3. Shen, L., and Tan, E.C. (2005b). Dimension Reduction-Based Penalized Logistic Regression for Cancer Classification Using Microarray Data. IEEE/ACM Transactions on Computational Biology and Bioinformatics 02, 166–175.
  4. Shen, L., and Tan, E.C. (2005c). Combining Kernel Dimension-Reduction with Regularized Classifiers for Tissue Categorization. Online Journal of Bioinformatics 6, 91–98.
  5. Shen, L., and Tan, E.C. (2006a). A Generalized Output-Coding Scheme with SVM for Multiclass Microarray Classification. (Imperial College Press), pp. 179–186.
  6. Shen, L., and Tan, E.C. (2006b). Reducing multiclass cancer classification to binary by output coding and SVM. Computational Biology and Chemistry 30, 63–71.

Meet the Team