Home  >>  Publications

Selected publications

A systematic evaluation of methods for tailoring genome-scale metabolic models. Cell Systems, 4, 1-12 (2017).

A consensus genome-scale reconstruction of Chinese hamster ovary cell metabolism. Cell Systems, 3, 434 (2016).

Predictive glycoengineering of biosimilars using a Markov chain glycosylation model. Biotechnology Journal,  (2016).

Rapid neurogenesis through transcriptional activation in human stem cells. Molecular Systems Biology, 10:760 (2014).

Genomic landscapes of Chinese hamster ovary cell lines as revealed by the Cricetulus griseus draft genome. Nature Biotechnology. 31:759 (2013).

Network context and selection in the evolution to enzyme specificityScience. 337:1101 (2012).

Constraining the metabolic genotype-phenotype relationship using a phylogeny of in silico methodsNature Reviews Microbiology. 10:291 (2012).

The Genomic Sequence of the Chinese Hamster Ovary (CHO) K1 cell lineNature Biotechnology, 29:735 (2011).

 Large-scale in silico modeling of metabolic interactions between cell types in the human brainNature Biotechnology, 28:1279 (2010).

All publications

corresponding author, * equal contribution
For a current list, click here.


55.  Spahn, P.N., Bath, T., Weiss, R.J., Kim, J., Esko, J.D., Lewis, N.E.‡, Harismendy, O.‡. PinAPL-Py: a web-service for the analysis of CRISPR-Cas9 Screens. BioRxiv (2017). DOI: 10.1101/147462

54.  Brunk, E.*, Chang, R.L., Xia, J., Hefzi, H., Yurkovich, J., Kim, D., Buckmiller, E., Wang, H.H., Yang, C., Palsson, B.Ø., Church, G.M., Lewis, N.E.*‡ Systemic post-translational control of bacterial systems regulates adaptation in dynamic environments. BioRxiv (2017). DOI: 10.1101/180646

53.  Richelle, A., Lewis, N.E.Improvements in protein production in mammalian cells from targeted metabolic engineering. Current Opinion in Systems Biology in press (2017). DOI: 10.1016/j.coisb.2017.05.019

52. Autran, C.A.*, Kellman, B. *, Asztalos, E., Blood, A., Hamilton Spense, E.C., Patel, A.L., Kim, J.H., Hou, J., Lewis, N.E., Bode, L. Human milk oligosaccharide composition predicts risk of necrotizing enterocolitis in preterm infants. Gut, in press. DOI: 10.1136/gutjnl-2016-312819

Highlighted in Nature Reviews Gastroenterology

51. Opdam, S.*, Richelle, A.*, Kellman, B., Li, S., Zielinski, D.C., Lewis, N.E.‡ A systematic evaluation of methods for tailoring genome-scale metabolic models. Cell Systems, 4:1-12 (2017). DOI:10.1016/j.cels.2017.01.010

50. Spahn, P.N., Hansen, A.H., Kol, S., Voldborg, B.G., Lewis, N.E.‡  Predictive glycoengineering of biosimilars using a Markov chain glycosylation model. Biotechnology Journal, 12:1600489 (2017). DOI:10.1002/biot.201600489

49. Kallehauge, T.B., Li, S., Pedersen, L.E., Ha, T.K., Ley, D., Andersen, M.R., Kildegaard, H.F., Lee, G.M.‡, Lewis, N.E.‡  Ribosome profiling-guided depletion of an mRNA increases cell growth rate and protein secretion. Scientific Reports7:40388 (2017). DOI:10.1038/srep40388

48. Shen, J.P., Zhao, D., Sasik, R., Luebeck, J., Birmingham, A., Bojorquez-Gomez, A., Licon, K., Klepper, K., Pekin, D., Beckett, A.N., Sanchez, K.S., Thomas, A., Kuo, C.C., Du, D., Roguev, A., Lewis, N.E., Chang, A.N., Kreisberg, J.F., Krogan, N., Qi, L., Ideker, T., Mali, P.M.  Combinatorial CRISPR–Cas9 screens for de novo mapping of genetic interactions. Nature Methodsin press (2017). DOI:10.1038/nmeth.4225

47. van Wijk, X.M., Döhrmann, S., Hallström, B.M., Li, S., Voldborg, B.G., Meng, B.X., McKee, K.K., van Kuppevelt, T.H., Yurchenco, P.D., Palsson, B.O., Lewis, N.E., Nizet, V., Esko, J.D. Whole Genome Sequencing of Invasion-Resistant Cells Identifies Laminin a2 as a Host Factor For Bacterial Invasion. mBio, 8:e02128-16 (2017). DOI:10.1128/mBio.02128-16

46. Lombardo, M.V., Courchesne, E., Lewis, N.E., Pramparo, T. Hierarchical cortical transcriptome disorganization in autism. Molecular Autism in press (2017). DOI: 10.1101/042937


45. Hefzi, H.*, Ang, K.S.*, Hanscho, M.*, Bordbar, A., Ruckerbauer, D., Lakshmanan, M., Orellana, C.A., Baycin-Hizal, D., Huang, H., Ley, D., Martínez, V.S., Kyriakopoulos, S., Jiménez, N.E., Zielinski, D.C., Quek, L.E., Wulff, T., Arnsdorf, J., Li, S., Lee, J.S., Paglia, G., Loira, N., Spahn, P.N., Pedersen, L.E., Gutierrez, J.M., King, Z.A., Lund, A.M., Nagarajan, H., Thomas, A., Abdel-Haleem, A.M., Zanghellini, J., Kildegaard, H.F., Voldborg, B.G., Gerdtzen, Z.P., Betenbaugh, M.J., Palsson, B.O., Andersen, M.R., Nielsen, L.K., Borth, N.‡, Lee, D.Y.‡, Lewis, N.E.‡ A consensus genome-scale reconstruction of Chinese hamster ovary cell metabolism. Cell Systems, 3, 434-443 (2016). DOI:10.1016/j.cels.2016.10.020

Press releases at, UCSD Health Sciences

44. Chiang, A.W.T., Li, S., Spahn, P.N., Richelle, A., Kuo, C.C., Samoudi, M.,  Lewis, N.E. Modulating carbohydrate-protein interactions through glycoengineering of monoclonal antibodies to impact cancer physiology. Current Opinion in Structural Biology, 10, 104–111 (2016). DOI: 10.1016/

43. Swainston, N., Smallbone, K., Hefzi, H., Dobson, P.D., Brewer, J., Hanscho, M., Zielinski, D.C., Ang, K.S., Gardiner, N.J., Gutierrez, J.M., Kyriakopoulos, S., Lakshmanan, M., Li, S., Liu, J.K., Martínez, V.S., Orellana, C.A., Quek, L.E., Thomas, A., Zanghellini, J., Borth, N., Lee, D.Y., Nielsen, L.K., Kell, D.B., Lewis, N.E., Mendes, P.  Recon 2.2: from reconstruction to model of human metabolism. Metabolomics, 12:109 (2016). DOI: 10.1007/s11306-016-1051-4

42. Huang, S., Chong, N., Lewis, N.E., Jia, W., Xie, G., Garmire, L.X. Novel personalized pathway-based metabolomics models reveal key metabolic pathways for breast cancer diagnosis. Genome Medicine, 8(1):1 (2016). DOI: 10.1186/s13073-016-0289-9

41. Golabgir, A.*, Gutierrez, J.M.*, Hefzi, H., Li, S., Palsson, B.O., Herwig, C.‡, Lewis, N.E.‡ Quantitative feature extraction from the Chinese Hamster Ovary bioprocess bibliome using a novel meta-analysis workflow . Biotechnology Advances, 34(5):621–633 (2016). DOI:10.1016/j.biotechadv.2016.02.011 * equal contribution, listed alphabetically The CHO Bibliome website

40. King, Z.A., Lu, J., Dräger, A., Miller, P., Federowicz, S., Lerman, J., Ebrahim, A., Palsson, B.O., Lewis, N.E.‡ BiGG Models: A platform for integrating, standardizing, and sharing genome-scale models.  Nucleic Acids Research, 44(D1):D515-22 (2016). DOI: 10.1093/nar/gkv1049 BiGG Models website

39. Spahn, P.N., Hansen, A.H., Hansen, H.G., Arnsdorf, J., Kildegaard, H.F., Lewis, N.E.‡  A Markov chain model for N-linked protein glycosylation – towards a low-parameter tool for model-driven glycoengineering. Metabolic Engineering,  33: 52–66 (2016). DOI:10.1016/j.ymben.2015.10.007


38. Pramparo, T., Campbell, K., Barnes, C.C., Marinero, S., Solso, S., Young, J., Mayo, M., Dale, A., Ahrens-Barbeau, C., Murray, S.S., Lopez, L., Lewis, N.E., Pierce, K., Courchesne, E.  Cell Cycle Networks link Gene Expression Dysregulation, Mutation and Brain Maldevelopment in Autistic Toddlers. Molecular Systems Biology,  11: 841 (2015). DOI:10.15252/msb.20156108

37. Ebrahim, A., Almaas, E., Bauer, E., Bordbar, A., Burgard, A.P., Chang, R.L., Dräger, A., Famili, I., Feist, A.M., Fleming, R.M.T., Fong, S.S., Hatzimanikatis, V., Herrgård, M.J., Holder, A., Hucka, M., Hyduke, D., Jamshidi, N., Lee, S.Y., Le Novère, N., Lerman, J.A., Lewis, N.E., Ma, D., Mahadevan, R., Maranas, C., Nagarajan, H., Navid, A., Nielsen, J., Nielsen, L.K., Nogales, J., Noronha, A., Pal, C., Palsson, B.O., Papin, J.A., Patil, K.R., Price, N.D., Reed, J., Saunders, M., Senger, R.S., Sonnenschein, N., Sun, Y., Thiele, I.  Do genome‐scale models need exact solvers or clearer standards?. Molecular Systems Biology, 11: 831 (2015). DOI: 10.15252/msb.20156157

36. Kumar, A., Baycin-Hizal, D., Wolozny, D., Pedersen, L.E., Lewis, N.E., Heffner, K., Chaerkady, R., Cole, R.N., Shiloach, J., Zhang, H., Bowen, M.A., Betenbaugh, M.J. Elucidation of the CHO Super-Ome (CHO-SO) by ProteoInfomatics.  Journal of Proteome Research, 14 (11), pp 4687–4703 (2015). DOI: 10.1021/acs.jproteome.5b00588

35. King, Z.A., Dräger, A., Ebrahim, A., Sonnenschein, N., Lewis, N.E., Palsson, B.OEscher: A web application for building, sharing, and embedding data-rich visualizations of biological pathways.  PLoS Computational Biology, 11:e1004321 (2015). DOI: 10.1371/journal.pcbi.1004321

34. Swann, J., Jamshidi, N., Lewis, N.E., Winzeler, E.A.Systems analysis of host–parasite interactions. WIREs: Systems Biology and Medicine, 7(6), 381–400 (2015). DOI: 10.1002/wsbm.1311

33. Gutierrez, J.M., Lewis, N.E.‡ Optimizing eukaryotic cell hosts for protein production through systems biotechnology and genome-scale modeling. Biotechnology Journal, 10:939–949 (2015). DOI: 10.1002/biot.201400647

32. Rodriguez, R.*, Thomas, A.*, Watanabe, L., Vazirabad, I.Y., Kofia, V., Gómez, H.F., Mittag, F., Matthes, J.,  Rudolph, J., Wrzodek, F., Netz, E., Diamantikos, A., Eichner, J., Keller, R., Wrzodek, C., Fröhlich, S., Lewis, N.E., Myers, C.J., Le Novère, N., Palsson, B.O., Hucka, M., Dräger,  A. JSBML 1.0: providing a smorgasbord of options to encode systems biology models. Bioinformatics, 31(20):3383-3386 (2015). DOI: 10.1093/bioinformatics/btv341

31. Lee, J.S., Grav, L.M., Lewis, N.E., Kildegaard, H.F. CRISPR/Cas9-mediated genome engineering of CHO cell factories: Application and perspectives. Biotechnology Journal, 10:979–994 (2015). DOI: 10.1002/biot.201500082.


30. Busskamp, V.*, Lewis, N.E.*, Guye, P.*, Ng, A.H.M., Shipman, S.L., Byrne, S.M., Sanjana, N.E., Murn, J., Li, Y., Li, S., Stadler, M., Weiss, R., Church, G.M. Rapid neurogenesis through transcriptional activation in human stem cells. Molecular Systems Biology, 10:760 (2014). DOI: 10.15252/msb.20145508. equal contribution

29. Spahn, P., Lewis, N.E.‡ Systems glycomics for glycoengineering. Current Opinion in Biotechnology, 30:218–224 (2014). DOI: 10.1016/j.copbio.2014.08.004

28. Hefzi, H., Lewis, N.E.‡ From random mutagenesis to systems biology in metabolic engineering of mammalian cells. Pharmaceutical Bioprocessing, 2:355-358 (2014). DOI: 10.4155/pbp.14.36

seq graphic

27. Kumar, A., Harrelson, T., Lewis, N.E., Gallagher, E., LeRoith, D., Shiloach, J., Betenbaugh, M.J.Multi-tissue computational modeling analyzes pathophysiology of Type 2 Diabetes in MKR mice. PLoS One, 9(7): e102319. DOI: 10.1371/journal.pone.0102319

26. Bordbar, A., Nagarajan, H., Lewis, N.E., Schellenberger, J., Latif, H., Federowicz, S., Ebrahim, A., Palsson, B.O. Minimal metabolic pathway structure is consistent with associated biomolecular interactionsMolecular Systems Biology, 10:737 (2014). DOI: 10.15252/msb.20145243

25. Robasky, K.*, Lewis, N.E.‡*, Church, G.M. The Role of Replicates for Error Mitigation in Next-Generation SequencingNature Reviews Genetics. 15:56–62 (2014). DOI: 10.1038/nrg3655  corresponding author, * equal contribution


evo graphic

24. Lewis, N.E.‡, Abdel-Haleem, A.M. The evolution of genome-scale models of cancer metabolismFront. Physiol. 4:237 (2013). DOI: 10.3389/fphys.2013.00237    corresponding author

23. Lewis, N.E.*, Liu, X.*, Li, Y.*, Nagarajan, H.*, Yerganian, G., O’Brien, E., Bordbar, A., Roth, A.M., Rosenbloom, J., Bian, C., Xie, M., Chen, W., Li, N., Baycin-Hizal, D., Latif, H., Forster, J., Betenbaugh, M.J., Famili, I., Xu, X., Wang, J., Palsson, B.O. Genomic landscapes of Chinese hamster ovary cell lines as revealed by the Cricetulus griseus draft genome. Nature Biotechnology. 31:759-65 (2013). doi: 10.1038/nbt.2624. * equal contribution

22. Kildegaard, H.F., Baycin-Hizal, D., Lewis, N.E., Betenbaugh, M.J. The Emerging CHO Systems Biology Era: Harnessing the ‘Omics Revolution for BiotechnologyCurrent Opinion in Biotechnology. S0958-1669(13):00021-9 (2013). doi: 10.1016/j.copbio.2013.02.007

21. Hyduke, D.R., Lewis, N.E., Palsson, B.Ø. Analysis of omics data with genome-scale models of metabolismMolecular BioSystems, 9:167 (2013). doi: 10.1039/c2mb25453k


pr graphic

20. Nam, H.J.*, Lewis, N.E.‡*, Lerman, J.A., Lee, D.H., Chang, R.L., Kim, D., Palsson, B.Ø.‡ Network context and selection in the evolution to enzyme specificityScience. 337:1101-1104 (2012).   corresponding author, * equal contribution

19. Noor, E.‡, Lewis, N.E.‡, Milo, R. A proof for loop-law constraints in stoichiometric metabolic networksBMC Systems Biology. 6:140 (2012). Highly Accessed.  corresponding author

18. Baycin-Hizal, D., Tabb, D.L., Chaerkady, R., Chen, L., Lewis, N.E., Nagarajan, H., Sarkaria, V., Kumar, A., Wolozny, D., Colao, J., Jacobson, E., Tian, Y., O’Malley, R.N., Krag, S., Cole, R.N., Palsson, B.O., Zhang, H., Betenbaugh, M.J. Proteomic analysis of Chinese hamster ovary cellsJournal of Proteome Research. 11:5265-76 (2012).

17. Hefzi, H., Palsson, B.Ø., Lewis, N.E.‡Reconstruction of genome-scale metabolic networks. In Handbook of Systems Biology. 229 (2013). doi:10.1016/B978-0-12-385944-0.00012-5  corresponding author

16. Lerman, J.A., Hyduke, D.R., Latif, H., Portnoy, V.A., Lewis, N.E., Orth, J.D., Schrimpe-Rutledge, A.C., Smith, R.D., Adkins, J.N., Zengler, K.A., Palsson, B.Ø. In silico method for modelling metabolism and gene product expression at genome scaleNature Communications. 3:929 (2012).

15. Lewis, N.E., Nagarajan, H., Palsson, B.Ø. Constraining the metabolic genotype-phenotype relationship using a phylogeny of in silico methodsNature Reviews Microbiology. 10:291-305 (2012). Click here for accompanying website with a catalog of constraint-based methods.


cho graphic

14. Xu, X.*, Nagarajan, H.*, Lewis, N.E.*, Pan, S.*,et al. The Genomic Sequence of the Chinese Hamster Ovary (CHO) K1 cell lineNature Biotechnology, 29:735-41 (2011). * equal contribution

13. Schellenberger, J., Que, R., Fleming, R.T., Thiele, I., Orth, J., Feist, A.M., Zielinski , D.C., Bordbar, A., Lewis, N.E., Rahmanian, S., Kang, J., Hyduke, D., Palsson, B.Ø. Quantitative prediction of cellular metabolism with constraint-based models: the COBRA Toolbox v2.0Nature Protocols, 6:1290-307 (2011).

12. Nam, H.J.*, Conrad, T.M., Lewis, N.E.*‡The role of cellular objectives and selective pressures in metabolic pathway evolutionCurrent Opinion in Biotechnology, 22:595-600 (2011). * equal contribution corresponding author

11. Conrad, T.M., Lewis, N.E., Palsson, B.Ø. Microbial Laboratory Evolution in the Era of Genome-Scale ScienceMolecular Systems Biology, 7:509 (2011).

10. Schellenberger, J., Lewis, N.E., Palsson, B.Ø. Elimination of thermodynamically infeasible loops in steady state metabolic modelsBiophysical Journal, 100:544-53 (2011).


brain graphic

9. Lewis, N.E., Schramm, G., Bordbar, A., Schellenberger, J., Andersen, M.P., Cheng, J.K., Patel, N., Yee, A., Lewis, R.A., Eils, R., König, R., Palsson, B.Ø. Large-scale in silico modeling of metabolic interactions between cell types in the human brainNature Biotechnology, 28:1279–1285 (2010). Paper highlighted by Nature Methods (January 2011).

8. Conrad, T.M., Frazier, M., Joyce, A.R., Cho, B. K., Knight, E. M., Lewis, N.E., Landick, R., Palsson, B.Ø. RNA polymerase mutants found through adaptive evolution re-program Escherichia coli K-12 MG1655 for optimal growth in minimal mediaProc. Nat. Acad. Sci. USA, 107:20500-5 (2010).

7. Bordbar, A., Lewis, N.E., Schellenberger, J., Palsson, B.Ø., Jamshidi, N. Insight into human alveolar macrophage and M. tuberculosis interactions via metabolic reconstructionsMolecular Systems Biology, 6:422 (2010).

6. Portnoy, V.A., Scott, D.A., Lewis, N.E., Tarasova, Y., Osterman, A.L., Palsson, B.Ø. Deletion of genes encoding cytochrome oxidases and quinol monooxygenase blocks the aerobic-anaerobic shift in Escherichia coli K-12 MG1655Appl. Environ. Microbiol., 76:6529-40 (2010).

5. Lewis, N.E., Hixson, K.K., Conrad, T.M., Lerman, J.A., Charusanti, P., Polpitiya, A.D., Adkins, J.N., Schramm, G., Purvine, S.O., Lopez-Ferrer, D., Weitz, K.K., Eils, R., König, R., Smith, R.D., Palsson, B.Ø. Omic data from evolved E. coli are consistent with computed optimal growth from genome-scale modelsMolecular Systems Biology, 6:390 (2010).

4. Bar-Even, A., Noor, E., Lewis, N.E., Milo, R. Design and analysis of synthetic carbon fixation pathwaysProc. Natl. Acad. Sci. USA., 107:8889-8894 (2010).


coli graphic

3. Lewis, N.E., Cho, B.K., Knight, E.M. Palsson, B. Ø. Gene expression profiling and the use of genome-scale in silico models of Escherichia coli for analysis: providing context for contentJ. Bacteriol., 191:3437-44 (2009).

2. Lewis, N.E., Jamshidi, N., Thiele, I. & Palsson, B.Ø. Metabolic systems biology: a constraint-based approach. In Encyclopedia of Complexity and Systems Science 5535 (Springer, New York, 2009). DOI:10.1007/978-3-642-27737-5_329-2


1. Merrell, K., Southwick, K., Graves, S.W., Esplin, M.S., Lewis, N.E., Thulin, C.D. Analysis of low-abundance, low-molecular-weight serum proteins using mass spectrometryJ. Biomol. Tech., 15:238-48 (2004).


3. Hefzi, H., Lewis, N.E. Patent pending – provisional.

2. Spahn, P., Lewis, N.E. Systems and methods for predicting glycosylation on proteins. WO Patent 2016187341 A1.

1. Herrgard, M. J., Pedersen, L.E., Lewis, N.E., Bruntse, A.B. Methods for modeling Chinese hamster ovary (CHO) cell metabolism. WO Patent WO2015010088-A1.