We study the genetic basis of human diseases using computational approaches and translate this knowledge to improve patient care. With a special emphasis on incorporating functional information, evolutionary history and population structure in biomarker discovery, our research goes beyond statistical associations to seek genetic markers with strong functional impact.
AREAS OF RESEARCH INTEREST

  • Develop and apply computational methods to enable precision medicine
    • Biomarker discovery
    • Cancer subclonal development
    • Personalized immunotherapy
  • Discover functional elements in human genomes and the indications in diseases
    • Fine-map causal noncoding variants
    • Gene-environment interaction in complex diseases
    • Regulatory rewiring via epigenetic evolution
  • Data analytics for biomedical applications
    • Statistical support to biomedical research
    • Software, databases and analytical pipelines to facilitate “omics” studies
PUBLICATIONS

 Journal articles: (§ indicates co-first-author)

  1. Liu L, Maxwell D, Patel R, Chandrashekar P, Gibson G, Kumar S. (2019) Biological relevance of predicted pathogenicity of noncoding variants. Nature Communications 10:330
  2. Jasbi P, Wang D, Cheng SL, Fei Q, Cui JY, Liu L, Wei Y, Raftery D, Gu H. (2019) Breast cancer detection using targeted plasma metabolomics. Journal of Chromatography B 1105:26-37
  3. Peter B, Dinu V, Liu L, Huentelman M, Naymik M, Lancaster H, Vose C, Schrauwen I (2019) Exome Sequencing of Two Siblings with Sporadic Autism Spectrum Disorder and Severe Speech Sound Disorder Suggests Pleiotropic and Complex Effects. Behavior Genetics.
  4. Liu L, Caselli R. (2018) Age stratification corrects bias in estimated hazards of APOE Genotype in Alzheimer’s disease. Alzheimer’s & Dementia TRCI 4:602–608
  5. Li C, Liu L, Dinu V. (2018) Pathways of topological rank analysis (potra): a novel method to detect pathways involved in cancer. PeerJ 6:e4571
  6. Arutla V, Leal J, Liu X, Sokalingam S, Raleigh M, Adaralegbe A, Liu L, Pentel P, Hecht S, Chang Y. (2017) Pre-screening of nicotine haptens in vitro to rank and select nicotine hapten-conjugate vaccines for in vivo functional tests. ACS Combinatorial Science 19(5):286-298
  7. Xie G, Chastain-Gross R, Belanger M, Kumar D, Whitlock J, Liu L, Farmerie W, Zeng C, Daligault H, Han C,, Brettin T, Progulske-Fox A. (2017) Genome sequence of Porphyromonas gingivalis Strain A7A1-28. Genome Announcement 5(10): e00021-17
  8. Liu L, Chang Y, Yang T, Noren DP, Amina Q, Kornblau S, Ye J. (2016) Evolution-informed Modeling Improves Outcome Prediction for Cancers. Evolutionary Applications 10(1):68-76
  9. Liu L, Tamura K, Sanderford M, Gray VE, Kumar S (2016) A Molecular Evolutionary Reference for the Human Variome. Molecular Biology and Evolution 33(1):245-54
  10. Szedlak A, Smith N, Liu L, Paternostro G, Piermarocchi C. (2016) Evolutionary and topological properties of genes and community structures in human gene regulatory network. PLoS Computational Biology 12(6):e1005009
  11. Noren DP, Long B, Norel R, Rhrissorrakrai K, Hess K, Hu W, Bisberg A, Schultz A, Engquist E, Liu L, Lin E, Chen, G, Xie H, Hunter G, Stepanov O, Norman T, Friend SH, Stolovitzky G, Kornboau S, Qutub AA. (2016) A Crowd Sourcing Approach to Developing and Assessing Prediction Algorithms for AML Prognosis. PLoS Computational Biology 12(6):e1004890
  12. Gerek ZN, Liu L, Gerold K, Biparva P, Thomas ED, Kumar S. (2015) Evolutionary Diagnosis of non-synonymous variants involved in differential drug response. BMC Medical Genomics 8;Suppl 1:S6
  13. Chastain-Gross RP, Xie G, Belanger M, Kumar D, Whitlock JA, Liu L, Farmerie G, Daligault HE, Han CS, Brettin TS, Progulske-Fox A. (2015) Genome sequence of porphyromonas gingivalis strain A7436. Genome Announcements 3(5).e00927
  14. Xie G, Chastain-Gross RP, Belanger M, Kumar D, Whitlock JA, Liu L, Farmerie G, Daligault HE, Han CS, Brettin TS, Progulske-Fox A. (2015) Genome sequence of porphyromonas gingivalis strain AJW4. Genome Announcements 3(6).e01304
  15. Kumar S, Liu L. (2014) No positive selection for G-allele in a p53 response element in Europeans. Cell 157(7):1497-1499
  16. Kumar S, Ye J, Liu L (2014) Reply to: “Proper reporting of predictor performance”. Nature Methods 11(8):781-2
  17. Gray VE, Liu L, Nirankari R, Hornbeck P, Kumar S (2014) Signatures of natural selection on mutations of residues with multiple posttranslational modifications. Molecular Biology and Evolution 31(7):1641-5
  18. Stecher G, Liu L, Sanderford M, Peterson D, Tamura K, Kumar S. (2014) MEGA-MD: molecular evolutionary genetics analysis software with mutational diagnosis of amino acid variation. Bioinformatics 30(9):1305-7
  19. Liu L, Kumar S. (2013) Evolutionary balancing is critical for correctly forecasting disease associated amino acid variants. Molecular Biology and Evolution 30(6):1252-7
  20. Wellensiek BP, Larsen AC, Stephens B, Kukurba K, Waern K, Briones N, Liu L, Snyder M, Jacobs BL, Kumar S, Chaput JC. (2013) Genome-wide profiling of human cap-independent translation-enhancing elements. Nature Methods 10(8):747-50
  21. Yin L, Hou W, Liu L, Cai Y, Wallet MA, Gardner BP, Chang K, Lowe AC, Rodriguez CA, Sriaroon P, Farmerie WG, Sleasman JW, Goodenow MM (2013) IgM repertoire biodiversity is reduced in HIV-1 infection and systemic lupus erythematosus. Frontiers in HIV and AIDS doi:10.3389/f2013.00373
  22. Kumar S, Sanderford M, Gray VE, Ye J, Liu L (2012) Evolutionary Diagnosis Method for Variants in Personal Exomes. Nature Methods 9(9):855-6
  23. Dudley JT, Kim Y, Liu L, Markov GJ, Gerold K, Chen R, Butte AJ, Kumar S (2011) Human Genomic Disease Variants: A Neutral Evolutionary Explanation. Genome Research doi:10.1101/gr.133702.111
  24. Kumar S, Dudley JT, Filipski A, Liu L (2011) Phylomedicine: an evolutionary telescope to explore and diagnose the universe of disease mutations. Trends in Genetics. 27(9):377-86.
  25. Yin L, Liu L, Sun Y, Hou W, Lowe AC, Gardner BP, Salemi M, Williams WB, Farmerie WG, Sleasman JW, Goodenow MM (2012) High-resolution deep sequencing reveals biodiversity, population structure, and persistence of HIV-1 quasispecies within host ecosystems. Retrovirology 9:108
  26. Aggelen GV, Ankley GT, Baldwin WS, Bearden DW, Benson WH, Chipman JK, Collette TW, Craft JA, Denslow ND, Embry MR, Falciani F, George SG, Helbing CC, Hoekstra PF, Iguchi T, Kagami Y, Katsiadaki I, Kille P, Liu L, Lord PG, McIntyre T, O’Neill A, Osachoff H, Perkins DJ, Santos EM, Skirrow RC, Snape JR, Tyler CR, Versteeg D, Viant M, Volz DC, Williams TD, Yu L, (2010) Integrating Omic Technologies into Aquatic Ecological Risk Assessment and Environmental Monitoring: Hurdles, Achievements, and Future Outlook, Environmental Health Perspectives. 118(1):1-5
  27. Spade DJ, Griffitt RJ, Liu L, Brown-Peterson NJ, Kroll KJ, Feswick a, Glazer RA, Barber DS, Denslow ND. (2010) Queen conch (Strombus gigas) testis regresses during the reproductive season at nearshore sites in the Florida Keys. PloS one 5(9):e12737
  28. Paul A, Liu L, Laughner B, McClung S, Chen S, Ferl R. (2009) Comparative Interactomics: Analysis of Arabidopsis 14-3-3 complexes reveals highly conserved 14-3-3 interactions between humans and plants. Journal of Proteome Research. 8:1913-1924
  29. Rosser CJ, Liu L, Sun Y, Villicana P, McCullers M, Porvasnik S, Young PR, Parker AS, Goodison S. (2009) Bladder cancer-associated gene expression signatures identified by profiling of exfoliated urothelia. Cancer Epidemiology, Biomarkers and Prevention 18(2):444-53.
  30. Duan YP, Zhou LJ, Hall DG, Li WB, Doddapaneni H, Lin H, Liu L, Sun Y, Gabriel DW, Vahling CM, Williams K, Dickerman A, Gottwald T. (2009) Complete genome sequence of citrus huanglongbing bacterium, ‘Candidatus Liberibacter asiaticus’ obtained through metagenomics, Molecular Plant-Microbe Interaction 22(8):1011-20
  31. Garcia-Reyero N, Kroll KJ, Liu L, Orlando EF, Watanabe KH, Sepúlveda MS, Villeneuve DL, Perkins EJ, Ankley GT, Denslow ND. (2009) Gene expression responses in male fathead minnows exposed to binary mixtures of an estrogen and antiestrogen. BMC Genomics. 13;10:308
  32. Sun Y, Cai YP, Liu L, Yu F, Farrell M, McKendree W, Farmerie WG. (2009) ESPRIT: estimating species richness using large collections of 16S rRNA shotgun sequences. Nucleic Acid Research 37(10):e76
  33. Yu F, Sun Y, Liu L, Farmerie WG. (2009) GSTaxClassifier: a genomic signature based taxonomic classifier for metagenomics data analysis. 4(1):46-49
  34. Garcia-Reyero N, Adelman I, Liu L, Denslow N. (2008) Gene expression profiles of fathead minnows exposed to surface waters above and below a sewage treatment plant in Minnesota. Marine Environmental Research 66(1):134-6.
  35. Garcia-Reyero N, Griffitt RJ, Liu L, Kroll KJ, Farmerie WG, Barber DS, Denslow ND. (2008) Construction of a robust microarray from a non-model species (largemouth bass) using pyrosequencing technology. Journal of Fish Biology 72(9):2354-2376
  36. Sun Y, Goodison S, Li J, Liu L, Farmerie WG. (2007) Improved breast cancer prognosis through the combination of clinical and genetic markers. Bioinformatics. 23(1):30-37
  37. Popp MP, Liu L, Timmers A, Esson DW, Shiroma L, Meyers C, Berceli S, Tao M, Wistow G, Schultz GS, Sherwood MB. (2007) Development of a Microarray Chip for Rabbit Ocular Research. Molecular Vision. 13:164-73
  38. Luo X, Pan Q, Liu L, Chegini N. (2007) Genomic and proteomic profiling II: Comparative assessment of gene expression profiles in leiomyomas, keloids, and surgically-induced scars. Reproductive Biology and Endocrinology 5(1):35
  39. Larkin P, Villeneuve DL, Knoebl I, Miracle AL, Carter BJ, Liu L, Denslow ND, Ankley GT. (2007) Development and validation of a 2,000-gene microarray for the fathead minnow (Pimephales promelas). Environmental Toxicology and Chemistry. 26(7):1497-506
  40. Moroz LL, Edwards JR, Puthanveettil SV, Kohn A, Ha T, Heyland A, Knudsen B, Sahni A, Yu F, Liu L, Jezzini S, Sadreyev R, Lovell P, Iannucculli W, Chen M, Nguyen T, Sheng H, Shaw R, Kalachikov S, Panchin Y, Farmerie WG, Russo JJ, Ju J, Kandel ER. (2006) The Neuronal Transcriptome of Aplysia californica: A Platform for the Neurogenomics of Defined Neurons, Neuronal Compartments and Neuronal Circuitry. 127(7):1453-1467
  41. Chao EM, Liu L, Farmerie WG, Keyhani NO (2006) EST analysis of cDNA libraries from the entomopathogenic fungus Beauveria (Cordyceps) bassiana. I. Evidence for stage-specific gene expression in aerial conidia, in vitro blastospores and submerged conidia. Microbiology. 152(Pt 9):2843-54.
  42. Gabriel DW, Allen C, Schell M, Denny TP, Greenberg JT, Duan Y, Flores-Cruz Z, Huang Q, Clifford JM, Presting G, Gonzalez ET, Reddy J, Elphinstone J, Swanson J, Yao J, Mulholland V, Liu L, Farmerie WG, Patnaikuni M, Balogh B, Norman D, Alvarez A, Castillo JA, Jones J, Saddler G, Walunas T, Zhukov A, Mikhailova N (2006) Identification of open reading frames unique to a Select Agent: Ralstonia solanacearum race 3 biovar 2. Molecular Plant-Microbe Interaction 19(1):69-79
  43. Farmerie WG, Hammer J, Liu L, Sahni A, Schneider M. (2005) Biological Workflow with BlastQuest. Data and Knowledge Engineering. 53(1):75-97
  44. Kornberg LJ, Villaret D, Popp MP, Liu L, McLaren R, Brown H, and McFadden M. (2005) Gene Expression Profiling in Squamous Cell Carcinoma of the Oral Cavity Shows Abnormalities in Several Signaling Pathways. Laryngoscope. 115(4):690-8
  45. Esson DW, Popp MP, Liu L, Schultz GS, Sherwood MB. (2004) Microarray analysis of the failure of filtering blebs in a rat model of glaucoma filtering surgery. Investigative Ophthalmology and Visual Science. 45(12):4450-62.
  46. Cousins RJ, Blanchard RK, Popp MP, Liu L, Cao J, Moore JB and Green CL. (2003) A Global View of the Selectivity of Zinc Deprivation and Excess on Genes Expressed in Human THP-1 Mononuclear Cells. Proceedings of the National Academy of Science 100:6952-6957
  47. Li YJ, Liu L, Zhang FC. (2003) The clinical significance of SSA antigen and its different positive expressions. Zhonghua Nei Ke Za Zhi. 42(3):165-8

 

Conference presentations:

  • Know-GRRF: domain-knowledge informed biomarker discovery with random forests. 6th International Work-conference on Bioinformatics and Biomedical Engineering. Granada, Spain. 2018
  • Biological adaptability as a biomarker for risk assessment. Arizona Alzheimer’s Consortium Annual Conference. Sedona, AZ, 2018
  • Fast fine mapping of causal eQTL variants. International Symposium on Molecular Evolution and Medicine, Philadelphia, PA, 2017
  • Evolution-informed Biomarker Discovery for Precision Oncology, 6th International Conference on Bioinformatics & Systems Biology, Philadelphia, PA, 2016
  • Evolution-informed modeling. RECOMB/ISCB Conference, San Diego, CA, 2014
  • An evolutionary diagnosis method for variants in personal exomes. Phylomedicine Symposium, Tempe, AZ, 2012
  • Having A BLAST with BlastQuest: Where Do We Go From Here? INFORMS Annual Meeting, Denver, CO, 2004

 

Conference proceedings:

  • Guan X, Liu L. Know-GRRF: Domain-Knowledge Informed Biomarker Discovery with Random Forests. 6th International Work-conference on Bioinformatics and Biomedical Engineering. Granada, Spain. 2018
  • Li Y, Wang J, Yang T, Chen J, Liu L, Zhan L, Hibar DP, Jahanshad N, Wang Y, Zhao S, Thompson PM, Ye J, (2016) Identification of Alzheimer’s Disease Risk Factors by Tree-Structured Group Lasso Screening. IEEE International Symposium on Biomedical Imaging
  • Yang T, Wang J, Sun Q, Hibar DP, Jahanshad N, Liu L, Wang Y, Zhan L, Thompson PM, Ye J (2015) Detecting genetic risk factors for Alzheimer’s disease in whole genome sequence data via lasso screening. IEEE International Symposium on Biomedical Imaging
  • Sun Y, Liu L, Popp M, Farmerie W. (2006) Estimation of Cross-hybridization Signals Using Support Vector Regression. IEEE Symp. of Computations in Bioinformatics and Bioscience (SCBB’06)
  • Goodison S, Popp M, Liu X, Farmerie WG, Casella G, Liu L (2006) A new meta-analysis method applied to prostate cancer profiles. Proceedings of American Association of Cancer Research, Volume 47

 

Conference posters:

  • Ahmadinejad N, Liu L. (2017) Decomposing cancer subclonal structures with model-based clustering. International Symposium on Molecular Evolution and Medicine, Philadelphia, PA,
  • Chandrasheka P, Elmas A, Liu L. (2017) Discover Immunosignature in Systemic Lupus Erythematosus. Biodesign Scientific Retreat, Scottsdale, AZ
  • Admadinejad N, Liu L. (2017) Model-base Hierarchical Clustering for Cancer Subclonal Detection. Biodesign Scientific Retreat, Scottsdale, AZ
  • Liu L, Zeng B, Kumar S, Gibson G. (2016) Discover eQTL with flexible LD structure and tree-guided group lasso, Pacific Symposium on Biocomputing, Waimea, HI
  • Liu L, Chang Y, Ye J, Kumar S. (2015) Distinct evolutionary and mutational patterns in oncogenes and tumor suppressor genes, AACR Annual Meeting, Philadelphia, PA