Computational Systems Biology and Bioinformatics Lab



  • Q Liu, H Di, L Xie (2018) "Identifying Context-specific Network Features for CRISPR-Cas9 Targeting Efficiency Using Accurate and Interpretable Deep Neural Network". BioRxiv, doi:
  • H Lim, D He, Y Qiu, P Krawczuk, X Sun (2018) "Rational Discovery of Dual-Action Multi-Target Kinase Inhibitor for Precision Anti-Cancer Therapy Using Structural Systems Pharmacology". BioRxiv, doi:
  • J Ji, Y He, L Xie (2018) "Dynamic Brain Connectivity Alternation Detection via Matrix-variate Differential Network Model". BioRxiv, doi:
  • Z Zhao, L Xie, PE Bourne(2018) "Structural insights into characterizing binding sites in EGFR kinase mutants". J Chem Inf Mod, in press
  • J Y He, J Ji, L Xie, X Zhang, F Xue (2018) "A new insight into underlying disease mechanism through semi-parametric latent differential network model". BMC Bioinformatics, 19(S17):493 [PDF]
  • H Lim, L Xie (2018) "Target Gene Prediction of Transcription Factor Using a New Neighborhood-regularized Tri-factorization One-class Collaborative Filtering Algorithm". Proceedings of the 2018 ACM International Conference on Bioinformatics, Computational Biology, and Health Informatics pp1-10.
  • A Poleksic, L Xie (2018) "Predicting serious rare adverse reactions of novel chemicals". Bioinformatics, 34(16):2835–284.
  • A Wang, H Lim, SY Cheng, L Xie (2018) "ANTENNA, a Multi-Rank, Multi-Layered Recommender System for Inferring Reliable Drug-Gene-Disease Associations: Repurposing Diazoxide as a Targeted Anti-Cancer Therapy". IEEE/ACM Transactions on Computational Biology and Bioinformatics, 15(6):1960-1967
  • H Lim, A Poleksic, L Xie (2018) "Exploring Landscape of Drug-Target-Pathway-Side Effect Associations". AMIA Summits on Translational Science Proceedings, 2017:132–141.


  • Q. Liu, C. Chen, A. Gao, HH. Tong, L. Xie (2017) "VariFunNet, an integrated multiscale modeling framework to study the effects of rare non-coding variants in genome-wide association studies: Applied to Alzheimer". 2017 IEEE International Conference on Bioinformatics and Biomedicine (BIBM). pp2177-2182.
  • A. Poleksic, C. Turner, R. Dalal, P. Gray, L. Xie (2017) "Mining FDA resources to compute population-specific frequencies of adverse drug reactions". 2017 IEEE International Conference on Bioinformatics and Biomedicine (BIBM). pp1809-1814.
  • Z.H. Ni, A. C. Yuksel, X.Y. Ni, M. I. Mandel, L. Xie (2017) "Confused or not Confused? Disentangling Brain Activity from EEG Data Using Bidirectional LSTM Recurrent Neural Networks". Proceedings of the 8th ACM International Conference on Bioinformatics, Computational Biology, and Health Informatics. pp241-246
  • A. Wang, H. Lim, S.-Y. Cheng, L. Xie (2017) "ANTENNA, a Multi-Rank, Multi-Layered Recommender System for Inferring Reliable Drug-Gene-Disease Associations: Repurposing Diazoxide as a Targeted Anti-Cancer Therapy". BioKDD'17. Halifax, Canada
  • J. Ji, D. He, Y. Feng, Y. He, F. Xue, L. Xie (2017) "JDINAC: joint density-based non-parametric differential interaction network analysis and classification using high-dimensional sparse omics data". Bioinformatics. 33(19):3080-3087
  • J. C. Chen, H.H. Tong, L. Xie, L, Ying, & Q. He (2017) "Cross-Dependency Inference in Multi-layered Networks: A Collaborative Filtering Perspective ". ACM TKDD. 11(4):article #42
  • Z. Zhao, L. Xie, P.E. Bourne (2017) "Insights into the binding mode of MEK type-III inhibitors. A step towards discovering and designing allosteric kinase inhibitors across the human kinome". PLoS One. 12(6):e0179936 [PDF]
  • Z. Zhao, Q. Liu, S. Bliven, L. Xie, P.E. Bourne (2017) "Determining cysteines available for covalent inhibition across the human kinome". J. Med. Chem. 60(7):2879-2889 [PDF]
  • L. Xie, E.J. Draizen, P.E. Bourne (2017) "Harnessing big data for systems pharmacology". Annu. Rev. Pharmacol. Toxicol. 57:245-262 [PDF]


  • H.-S. Lim, P. Gary, L. Xie, A. Poleksic (2016) "Improved genome-scale multi-target virtual screening via a novel collaborative filtering approach to cold-start problem". Sci. Rep.. 6:38860 [PDF]
  • S. Dider, J.D. Ji, Z. Zhao, L. Xie (2016) "Molecular Mechanisms Involved in the Side Effects of Fatty Acid Amide Hydrolase Inhibitors: A Structural Phenomics Approach to Proteome-wide Cellular Off-target Deconvolution and Disease Association". npj Sys Biol Appl, 2:16023 [PDF]
  • H.-S. Lim, A. Poleksic, Y. Yao, H. Tong, L. Zhuang, P. Meng, L. Xie (2016) "Large scale off-target prediction using an accurate and efficient one-class collaborative filtering algorithm and its application to drug repurposing". PLoS Comp Biol. 12(10):e1005135 [PDF]
  • C. Chen, H.H. Tong, L. Xie, L, Ying, & Q. He (2016) "FASCINATE: Fast Cross-Layer Dependency Inference on Multi-layered Networks". In the Proceedings of 22th ACM SIGKDD International Conference on Knowledge Discovery and Data Mining, San Francisco, USA, August, 2016, (KDD2016) [PDF]
  • S. H. Chiu, L. Xie (2016) "Toward high-throughput predictive modeling of protein binding/unbinding kinetics". JCIM, 56(6):1164–1174 [PDF]
  • Z. Zhao, L. Xie, L. Xie, P. E. Bourne (2016) "Delineation of polypharmacology across the human structural kinome using a functional site interaction fingerprint approach". J Med Chem. 59(9):4326-41 [PDF]
  • G. I. Allen, Amoroso N. Amoroso, Anghel G. Anghel et al. (2016) "Crowdsourced estimation of cognitive decline and resilience in Alzermer’s disease". Alzheimer’s & Dementia, 12(6):645-53.
  • J. Lhota, L. Xie (2016) "Protein fold recognition using an improved single source k diverse shortest paths algorithm". Proteins, 84(4):467-72 [PDF]
  • T. Hart, S. Diber, W. Han, H. Xu, Z. Zhao, L Xie (2016) "Toward repurposing metformin as a precision anti-cancer therapy using structural systems pharmacology". Sci Rep. , 6:20441 [PDF]
  • T. Hart, L Xie (2016) "Providing data science support for systems pharmacology and its implications to drug discovery". Expert Opin Drug Discov., 11(3):241-256 [PDF]
  • Z. Zhao, C. Martin, R. Fan, P. E. Bourne, L Xie (2016) "Drug repurposing to target Ebola virus replication and virulence using structural systems pharmacology". BMC Bioinformatics, 17(1):90 [PDF]
  • C. Wang, G. Hu, K. Wang, M. Brylinski, L. Xie, L. Kurgan (2016) "PDID: database of molecular-level putative protein-drug interactions in the structural human proteome". Bioinformatics, 32(4):579-86 [PDF]
  • Y. Zhang, L. Xie, L. Xie & P. E.Bourne (2016) "The Plasmodium falciparum Drugome and its Polypharmacological Implications" BioRxiv doi: [PDF]


  • L. Xie and P. E. Bourne (2015) "Developing multi-target therapeutics to fine-tune the evolutionary dynamics of the cancer ecosystem". Front. Pharmacol. 6:209. doi: 10.3389/fphar.2015.00209 [PDF]
  • L.-C. L. Tsai, L. Xie, K. Dore, L. Xie, J. C. Del Rio, C. C. King, G. MartinezAriza, C. Hulme, R. Malinow, P. E. Bourne, A. C. Newton (2015) "Zeta inhibitory peptide disrupts electrostatic interactions that maintain atypical protein kinase C in its active conformation on the scaffold p62". J. Biol. Chem, 290(36):21845-56. [PDF]
  • J. Lhota, R. Hauptman, T. Hart, C. Ng, L. Xie (2015) "A new method to improve network topological similarity search: applied to fold recognition", Bioinformatics, 31(13):2106-14. [PDF]
  • Y. Liu, H. Tong, L. Xie, Y. Tang (2015) "Supervised Link Prediction Using Random Walks ". Social Media Processing, 568:pp107-118 [PDF]


  • L. Xie, X. Ge, H. Tan, L. Xie, Y. Zhang, T. Hart, X. Yan, P. E. Bourne (2014) "Toward Structural Systems Pharmacology to Study Complex Diseases and Personalized Medicine". PLoS Comp Biol, 10(5):e1003554. [PDF]
  • C. Ng, Y. Zhang, P. E. Bourne & L. Xie (2014) "Anti-infectious Drug Repurposing Using an Integrated Chemical Genomics and Structural Systems Biology Approach", Pacific Symposium on Biocomputing, 19:136-47. [PDF]
  • T. Evangelidis, L. Xie (2014) "An integrated workflow for proteome-wide off-target identification and polypharmacology drug design". Tsinghua Science and Technology, 19(3):275-284. [PDF]


  • R. Chang, L. Xie, P.E. Bourne, B. Palsson (2013) "Antibacterial Mechanisms Identified Through Structural Systems Pharmacology". BMC Syst. Biol. 7:102 [PDF]
  • H. Tan, X. Ge, L. Xie (2013) "Structural Systems Pharmacology: a New Frontier in Discovering Novel Drug Targets". Curr Drug Targets, 14:952-956. [Link]
  • L. Xie, C. Ng, T. Ali, V. Valencia, B.L. Ferreira, V. Xue, M. Tanweer, D. Zhou, G. Haddad, P. E. Bourne, L. Xie.(2013) "Multiscale Modeling of the Causal Functional Roles of nsSNPs in a Genome-Wide Association Study: Application to Hypoxia". BMC Genomics 14(S3):S9 [PDF]
  • S. L. Epstein, X. Yun, L. Xie L (2013) "Multi-Agent, Multi-Case-Based Reasoning". Lecture Notes in Computer Science, Vol7969: 74-88 [Link]
  • G. Daniel, S.L. Kinnings, L. Xie, L. Xie, Y. Zhang, P. E. Bourne, and Y. Gil (2013) "Quantifying Reproducibility in Computational Biology: The Case of the Tuberculosis Drugome". PLoS One 8(11):e80278 [PDF]


  • L. Xie, S.L. Kinnings, L. Xie and P.E. Bourne (2012) Predicting the Polypharmacology of Drugs: Identifying New Uses Through Cheminformatics, Structural Informatics and Molecular Modeling-based Approaches in Drug Repurposing M. Barrett and D. Frail (Eds.) Chap. 7, 163-194, Wiley and Sons.
  • S.J. Ho Sui, R. Lo, R. Fernandes, M.DG.Caulfield, J. Lerman, L. Xie, P.E. Bourne, D.L.Baillie and F.S.L.Brinkman (2012) "Raloxifene attenuates Pseudomonas aeruginosa pyocyanin production and virulence". Int. J. of Antimicrobial Agents 40(3):246-251 [PDF].
  • L. Xie, L. Xie, S. L. Kinnings, and P.E. Bourne (2012) "Novel Computational Approaches to Polypharmacology as a Means to Define Responses to Individual Drugs". Annu. Rev. Pharmacol. Toxicol. 52: 361-379 [PDF].


  • L. Xie, T. Evangelidis, L. Xie and P.E. Bourne (2011) "Drug Discovery Using Chemical Systems Biology: Weak inhibition of multiple kinases may contribute to the anti-cancer effect of Nelfinavir". PLoS Comp. Biol. 7(4) e1002037 [PDF].
    (Comments: Science 2011 332(6030) 648-649 [Link])
  • L. Xie, L. Xie and P.E. Bourne (2011) "Structure-based Systems Biology for Analyzing Off-target Binding". Curr. Opinions in Struct. Biol. 21(2):189-199 [PDF].
  • S.L. Kinnings, N. Liu, P.J. Tonge, R.M. Jackson, L. Xie and P.E.Bourne (2011) "A Machine Learning Based Method to Improve Docking Scoring Functions and its Application to Drug Repurposing". J. Chem. Info. Model. 51(2):408-419 [PDF].


  • S.L. Kinnings, L. Xie, K.H.Fung, R.M. Jackson, L. Xie and P.E. Bourne (2010) "The Mycbacterium tuberculosis druggome and its Pharmaceutical Implications". Plos Comp. Biol. 6(11): e1000976 [PDF]
  • R.L Chang, L. Xie, L. Xie, P.E. Bourne B.O. Palsson (2010) "Drug Off-Target Effects Predicted Using Structural Analysis in the Context of a Metabolic Network Model". Plos Comp. Biol. 6(9): e1000938 [PDF]
  • J. Ren, L. Xie, W. Li, P. E. Bourne (2010) "SMAP-WS: A Parallel Web Service for Structural Proteome-Wide Ligand Binding Site Comparison.". Nucleic Acids Res., 38(Suppl):W441-4 [PDF]
  • J. D. Durrant, R. E. Amaro, L. Xie, M. D. Urbaniak, M. A. J. Ferguson, A. Haapalainen, Z. Chen, A. M. Di Guilmi, F. Wunder, P. E. Bourne, J. A. McCammon (2010) "A Multidimensional Strategy to Detect Polypharmacological Targets in the Absence of Structural and Sequence Homology". PLoS Comp. Biol., 6(1):e1000648 [PDF]


  • S. Kinnings, N. Liu, N. Buchmeier, P.J. Tonge, L. Xie and P.E. Bourne (2009) "Drug discovery using chemical systems biology: repositioning the safe medicine Comtan to treat multi-drug and extensively drug resistant tuberculosis". PLoS Comp. Biol., 5(7):e1000423 [PDF]
  • L. Xie, J. Li, L. Xie and P.E. Bourne (2009) "Drug Discovery Using Chemical Systems Biology: Identification of the Protein-Ligand Binding Network To Explain the Side Effects of CETP Inhibitors". PLoS Comp. Biol., 5(5):e1000387 [PDF]
  • L. Xie, L. Xie and P.E. Bourne (2009) "A unified statistical model to support local sequence order independent similarity searching for ligand binding sites and its application to genome-based drug discovery". Bioinformatics, 25(12):i305-i312 [PDF]


  • L. Xie and P.E. Bourne (2008) "Detecting Evolutionary Relationships Across Existing Fold Space, Using Sequence Order Independent Profile-profile Alignments". PNAS, 105(14):5441 [PDF]


  • L. Xie, J. Wang and P.E. Bourne (2007) "In Silico Elucidation of the Molecular Mechanism Defining the Adverse Effect of Selective Esterogen Receptor Modulators". PLoS Comp. Biol., 3(11):e217 [PDF].
  • L. Xie, and P.E. Bourne (2007) "A Robust and Efficient Algorithm for the Shape Description of Protein Structures and Its Application in Predicting Ligand Binding Sites". BMC Bioinformatics, 8(Suppl 4):S9 [PDF].


  • A. Kouranov, L. Xie, J. de la Cruz, L. Chen, J. Westbrook, P.E. Bourne, H.M. Berman (2006) "The RCSB PDB information portal for structural genomic". Nucleic Acids Res., 34(Database issue):D302-305 [PDF].


  • L. Xie and P.E. Bourne (2005) "Functional coverage of the human genome by existing structures, structural genomics targets, and homology models". PLoS Comp. Biol., 1(3):e31 [PDF].
  • N. Deshpande, K.J. Addess, W.F. Bluhm, J.C. Merino-Ott, W. Townsend-Merino, Q. Zhang, C. Knezevich, L. Xie, L. Chen, Z. Feng, R.K. Green, J.L. Flippen-Anderson, J. Westbrook, H.M. Berman, P.E. Bourne (2005) " The RCSB Protein Data Bank: a redesigned query system and relational database based on the mmCIF schema". Nucleic Acids Res., 33(Database issue):D233-237 [PDF].


  • C.L. Tang, L. Xie, I.Y. Koh, S. Posy, E. Alexov, B. Honig (2003) "On the role of structural information in remote homology detection and sequence alignment: new methods using hybrid sequence profiles". J. Mol. Biol., 334(5):1043-1062.
  • D. Petrey, Z. Xiang, C.L. Tang, L. Xie, M. Gimpelev, T. Mitros, C.S. Soto, S. Goldsmith-Fischman, A. Kernytsky, A. Schlessinger, I.Y. Koh, E. Alexov, B. Honig (2003) " Using multiple structure alignments, fast model building, and energetic analysis in fold recognition and homology modeling". Proteins, 53(S6):430-435.