@article{john_huntress_smith_chou_tollison_covarrubias_crisci_carpenter_peng_2024, title={Human long noncoding RNA,VILMIR,is induced by major respiratory viral infections and modulates the host interferon response}, url={https://doi.org/10.1101/2024.03.25.586578}, DOI={10.1101/2024.03.25.586578}, abstractNote={ABSTRACT}, author={John, Kristen and Huntress, Ian and Smith, Ethan and Chou, Hsuan and Tollison, Tammy S. and Covarrubias, Sergio and Crisci, Elisa and Carpenter, Susan and Peng, Xinxia}, year={2024}, month={Mar} } @article{brochu_smith_jeong_carlson_hansen_tisoncik-go_law_picker_gale_peng_2024, title={Pre-challenge gut microbial signature predicts RhCMV/SIV vaccine efficacy in rhesus macaques}, url={https://doi.org/10.1101/2024.02.27.582186}, DOI={10.1101/2024.02.27.582186}, abstractNote={ABSTRACT}, author={Brochu, Hayden N. and Smith, Elise and Jeong, Sangmi and Carlson, Michelle and Hansen, Scott G. and Tisoncik-Go, Jennifer and Law, Lynn and Picker, Louis J. and Gale, Michael, Jr. and Peng, Xinxia}, year={2024}, month={Feb} } @article{brochu_wang_tollison_pyo_thomas_tseng_law_picker_gale_geraghty_et al._2022, title={Alternative splicing and genetic variation of mhc-e: implications for rhesus cytomegalovirus-based vaccines}, volume={5}, ISSN={["2399-3642"]}, url={https://doi.org/10.1038/s42003-022-04344-2}, DOI={10.1038/s42003-022-04344-2}, abstractNote={Abstract}, number={1}, journal={COMMUNICATIONS BIOLOGY}, author={Brochu, Hayden and Wang, Ruihan and Tollison, Tammy and Pyo, Chul-Woo and Thomas, Alexander and Tseng, Elizabeth and Law, Lynn and Picker, Louis J. and Gale, Michael and Geraghty, Daniel E. and et al.}, year={2022}, month={Dec} } @article{wu_jiang_zou_sun_wu_cui_huntress_peng_li_2022, title={Coupling high-throughput mapping with proteomics analysis delineates cis-regulatory elements at high resolution}, volume={50}, ISSN={["1362-4962"]}, DOI={10.1093/nar/gkab890}, abstractNote={Abstract}, number={1}, journal={NUCLEIC ACIDS RESEARCH}, author={Wu, Ting and Jiang, Danli and Zou, Meijuan and Sun, Wei and Wu, Di and Cui, Jing and Huntress, Ian and Peng, Xinxia and Li, Gang}, year={2022}, month={Jan} } @article{huang_callahan_wu_holloway_brochu_lu_peng_tzeng_2022, title={Phylogeny-guided microbiome OTU-specific association test (POST)}, volume={10}, ISSN={["2049-2618"]}, DOI={10.1186/s40168-022-01266-3}, abstractNote={Abstract}, number={1}, journal={MICROBIOME}, author={Huang, Caizhi and Callahan, Benjamin John and Wu, Michael C. and Holloway, Shannon T. and Brochu, Hayden and Lu, Wenbin and Peng, Xinxia and Tzeng, Jung-Ying}, year={2022}, month={Jun} } @article{liu_hufnagel_catherine m. o'connell_goonetilleke_mokashi_waterboer_tollison_peng_wiesenfeld_hillier_et al._2022, title={Reduced Endometrial Ascension and Enhanced Reinfection Associated With Immunoglobulin G Antibodies to Specific Chlamydia trachomatis Proteins in Women at Risk for Chlamydia}, volume={225}, ISSN={["1537-6613"]}, DOI={10.1093/infdis/jiab496}, abstractNote={Abstract}, number={5}, journal={JOURNAL OF INFECTIOUS DISEASES}, author={Liu, Chuwen and Hufnagel, Katrin and Catherine M. O'Connell and Goonetilleke, Nilu and Mokashi, Neha and Waterboer, Tim and Tollison, Tammy S. and Peng, Xinxia and Wiesenfeld, Harold C. and Hillier, Sharon L. and et al.}, year={2022}, month={Mar}, pages={846–855} } @article{walsh_tollison_brochu_shaw_diveley_chou_law_kirk_gale_peng_2022, title={Single-Cell-Based High-Throughput Ig and TCR Repertoire Sequencing Analysis in Rhesus Macaques}, volume={208}, ISSN={["1550-6606"]}, url={https://doi.org/10.4049/jimmunol.2100824}, DOI={10.4049/jimmunol.2100824}, abstractNote={Abstract}, number={3}, journal={JOURNAL OF IMMUNOLOGY}, author={Walsh, Evan S. and Tollison, Tammy S. and Brochu, Hayden N. and Shaw, Brian I and Diveley, Kayleigh R. and Chou, Hsuan and Law, Lynn and Kirk, Allan D. and Gale, Michael, Jr. and Peng, Xinxia}, year={2022}, month={Feb}, pages={762–771} } @article{dawson_rasmussen_peng_lanzas_2021, title={Inferring environmental transmission using phylodynamics: a case-study using simulated evolution of an enteric pathogen}, volume={18}, ISSN={["1742-5662"]}, url={https://doi.org/10.1098/rsif.2021.0041}, DOI={10.1098/rsif.2021.0041}, abstractNote={Indirect (environmental) and direct (host–host) transmission pathways cannot easily be distinguished when they co-occur in epidemics, particularly when they occur on similar time scales. Phylodynamic reconstruction is a potential approach to this problem that combines epidemiological information (temporal, spatial information) with pathogen whole-genome sequencing data to infer transmission trees of epidemics. However, factors such as differences in mutation and transmission rates between host and non-host environments may obscure phylogenetic inference from these methods. In this study, we used a network-based transmission model that explicitly models pathogen evolution to simulate epidemics with both direct and indirect transmission. Epidemics were simulated according to factorial combinations of direct/indirect transmission proportions, host mutation rates and conditions of environmental pathogen growth. Transmission trees were then reconstructed using the phylodynamic approach SCOTTI (structured coalescent transmission tree inference) and evaluated. We found that although insufficient diversity sets a lower bound on when accurate phylodynamic inferences can be made, transmission routes and assumed pathogen lifestyle affected pathogen population structure and subsequently influenced both reconstruction success and the likelihood of direct versus indirect pathways being reconstructed. We conclude that prior knowledge of the likely ecology and population structure of pathogens in host and non-host environments is critical to fully using phylodynamic techniques.}, number={179}, journal={JOURNAL OF THE ROYAL SOCIETY INTERFACE}, author={Dawson, Daniel and Rasmussen, David and Peng, Xinxia and Lanzas, Cristina}, year={2021}, month={Jun} } @article{barrenas_hansen_law_driscoll_green_smith_chang_golez_urion_peng_et al._2021, title={Interleukin-15 response signature predicts RhCMV/SIV vaccine efficacy}, volume={17}, ISSN={["1553-7374"]}, url={https://doi.org/10.1371/journal.ppat.1009278}, DOI={10.1371/journal.ppat.1009278}, abstractNote={Simian immunodeficiency virus (SIV) challenge of rhesus macaques (RMs) vaccinated with strain 68–1 Rhesus Cytomegalovirus (RhCMV) vectors expressing SIV proteins (RhCMV/SIV) results in a binary outcome: stringent control and subsequent clearance of highly pathogenic SIV in ~55% of vaccinated RMs with no protection in the remaining 45%. Although previous work indicates that unconventionally restricted, SIV-specific, effector-memory (EM)-biased CD8+ T cell responses are necessary for efficacy, the magnitude of these responses does not predict efficacy, and the basis of protection vs. non-protection in 68–1 RhCMV/SIV vector-vaccinated RMs has not been elucidated. Here, we report that 68–1 RhCMV/SIV vector administration strikingly alters the whole blood transcriptome of vaccinated RMs, with the sustained induction of specific immune-related pathways, including immune cell, toll-like receptor (TLR), inflammasome/cell death, and interleukin-15 (IL-15) signaling, significantly correlating with subsequent vaccine efficacy. Treatment of a separate RM cohort with IL-15 confirmed the central involvement of this cytokine in the protection signature, linking the major innate and adaptive immune gene expression networks that correlate with RhCMV/SIV vaccine efficacy. This change-from-baseline IL-15 response signature was also demonstrated to significantly correlate with vaccine efficacy in an independent validation cohort of vaccinated and challenged RMs. The differential IL-15 gene set response to vaccination strongly correlated with the pre-vaccination activity of this pathway, with reduced baseline expression of IL-15 response genes significantly correlating with higher vaccine-induced induction of IL-15 signaling and subsequent vaccine protection, suggesting that a robust de novo vaccine-induced IL-15 signaling response is needed to program vaccine efficacy. Thus, the RhCMV/SIV vaccine imparts a coordinated and persistent induction of innate and adaptive immune pathways featuring IL-15, a known regulator of CD8+ T cell function, that support the ability of vaccine-elicited unconventionally restricted CD8+ T cells to mediate protection against SIV challenge.}, number={7}, journal={PLOS PATHOGENS}, publisher={Public Library of Science (PLoS)}, author={Barrenas, Fredrik and Hansen, Scott G. and Law, Lynn and Driscoll, Connor and Green, Richard R. and Smith, Elise and Chang, Jean and Golez, Inah and Urion, Taryn and Peng, Xinxia and et al.}, editor={Silvestri, GuidoEditor}, year={2021}, month={Jul} } @article{barrenäs_hansen_law_driscoll_green_smith_chang_golez_urion_peng_et al._2021, title={Sustained IL-15 response signature predicts RhCMV/SIV vaccine efficacy}, volume={1}, url={https://doi.org/10.1101/2021.01.11.426199}, DOI={10.1101/2021.01.11.426199}, abstractNote={Abstract}, publisher={Cold Spring Harbor Laboratory}, author={Barrenäs, Fredrik and Hansen, Scott G. and Law, Lynn and Driscoll, Connor and Green, Richard R. and Smith, Elise and Chang, Jean and Golez, Inah and Urion, Taryn and Peng, Xinxia and et al.}, year={2021}, month={Jan} } @article{nagarajan_cho_gyorke_nagarajan_ezzell_brochu_huntress_harrell_peng_2021, title={Tumor Necrosis Factor Alpha-Induced Interleukin-1 Alpha Synthesis and Cell Death Is Increased in Mouse Epithelial Cells Infected With Chlamydia muridarum}, volume={224}, ISSN={["1537-6613"]}, DOI={10.1093/infdis/jiab168}, abstractNote={Abstract}, journal={JOURNAL OF INFECTIOUS DISEASES}, author={Nagarajan, Uma M. and Cho, Crescentia and Gyorke, Clare E. and Nagarajan, Shanmugam and Ezzell, J. Ashley and Brochu, Hayden and Huntress, Ian and Harrell, Erin and Peng, Xinxia}, year={2021}, month={Aug}, pages={S47–S55} } @article{dinh_paudel_brochu_popowski_gracieux_cores_huang_hensley_harrell_vandergriff_et al._2020, title={Inhalation of lung spheroid cell secretome and exosomes promotes lung repair in pulmonary fibrosis}, volume={11}, ISSN={["2041-1723"]}, url={http://dx.doi.org/10.1038/s41467-020-14344-7}, DOI={10.1038/s41467-020-14344-7}, abstractNote={Abstract}, number={1}, journal={NATURE COMMUNICATIONS}, publisher={Springer Science and Business Media LLC}, author={Dinh, Phuong-Uyen C. and Paudel, Dipti and Brochu, Hayden and Popowski, Kristen D. and Gracieux, M. Cyndell and Cores, Jhon and Huang, Ke and Hensley, M. Taylor and Harrell, Erin and Vandergriff, Adam C. and et al.}, year={2020}, month={Feb} } @article{brochu_tseng_smith_thomas_jones_diveley_law_hansen_picker_gale_et al._2020, title={Systematic Profiling of Full-Length Ig and TCR Repertoire Diversity in Rhesus Macaque through Long Read Transcriptome Sequencing}, volume={204}, ISSN={["1550-6606"]}, DOI={10.4049/jimmunol.1901256}, abstractNote={Abstract}, number={12}, journal={JOURNAL OF IMMUNOLOGY}, author={Brochu, Hayden N. and Tseng, Elizabeth and Smith, Elise and Thomas, Matthew J. and Jones, Aiden M. and Diveley, Kayleigh R. and Law, Lynn and Hansen, Scott G. and Picker, Louis J. and Gale, Michael, Jr. and et al.}, year={2020}, month={Jun}, pages={3434–3444} } @article{martinez_fong_li_yang_jennewein_weiner_harrell_mangold_goswami_seage_et al._2019, title={Fc Characteristics Mediate Selective Placental Transfer of IgG in HIV-Infected Women}, volume={178}, ISSN={["1097-4172"]}, DOI={10.1016/j.cell.2019.05.046}, abstractNote={The placental transfer of maternal IgG is critical for infant protection against infectious pathogens. However, factors that modulate the placental transfer of IgG remain largely undefined. HIV-infected women have impaired placental IgG transfer, presenting a unique “disruption model” to define factors that modulate placental IgG transfer. We measured the placental transfer efficiency of maternal HIV and pathogen-specific IgG in US and Malawian HIV-infected mothers and their HIV-exposed uninfected and infected infants. We examined the role of maternal HIV disease progression, infant factors, placental Fc receptor expression, IgG subclass, and glycan signatures and their association with placental IgG transfer efficiency. Maternal IgG characteristics, such as binding to placentally expressed Fc receptors FcγRIIa and FcγRIIIa, and Fc region glycan profiles were associated with placental IgG transfer efficiency. Our findings suggest that Fc region characteristics modulate the selective placental transfer of IgG, with implications for maternal vaccine design and infant health.}, number={1}, journal={CELL}, author={Martinez, David R. and Fong, Youyi and Li, Shuk Hang and Yang, Fang and Jennewein, Madeleine F. and Weiner, Joshua A. and Harrell, Erin A. and Mangold, Jesse F. and Goswami, Ria and Seage, George R., III and et al.}, year={2019}, month={Jun}, pages={190-+} } @article{li_gilbert_carpp_pyo_janes_fong_shen_neidich_goodman_decamp_et al._2019, title={Fc Gamma Receptor Polymorphisms Modulated the Vaccine Effect on HIV-1 Risk in the HVTN 505 HIV Vaccine Trial}, volume={93}, ISSN={["1098-5514"]}, DOI={10.1128/JVI.02041-18}, abstractNote={By analyzing data from the HVTN 505 efficacy trial of a DNA/recombinant adenovirus 5 (rAd5) vaccine regimen, we found that host genetics, specifically Fc gamma receptor genetic variations, influenced whether receiving the DNA/rAd5 regimen was beneficial, neutral, or detrimental to an individual with respect to HIV-1 acquisition risk. Moreover, Fc gamma receptor genetic variations influenced immune responses to the DNA/rAd5 vaccine regimen. Thus, Fc gamma receptor genetic variations should be considered in the analysis of future HIV vaccine trials and the development of HIV vaccines.}, number={21}, journal={JOURNAL OF VIROLOGY}, author={Li, Shuying S. and Gilbert, Peter B. and Carpp, Lindsay N. and Pyo, Chul-Woo and Janes, Holly and Fong, Youyi and Shen, Xiaoying and Neidich, Scott D. and Goodman, Derrick and deCamp, Allan and et al.}, year={2019}, month={Nov} } @article{barrenas_raehtz_xu_law_green_silvestri_bosinger_nishida_li_lu_et al._2019, title={Macrophage-associated wound healing contributes to African green monkey SIV pathogenesis control}, volume={10}, ISSN={["2041-1723"]}, DOI={10.1038/s41467-019-12987-9}, abstractNote={Abstract}, journal={NATURE COMMUNICATIONS}, author={Barrenas, Fredrik and Raehtz, Kevin and Xu, Cuiling and Law, Lynn and Green, Richard R. and Silvestri, Guido and Bosinger, Steven E. and Nishida, Andrew and Li, Qingsheng and Lu, Wuxun and et al.}, year={2019}, month={Nov} } @article{catherine m. o'connell_brochu_girardi_harrell_jones_darville_sena_peng_2019, title={Simultaneous profiling of sexually transmitted bacterial pathogens, microbiome, and concordant host response in cervical samples using whole transcriptome sequencing analysis}, volume={6}, ISSN={["2311-2638"]}, DOI={10.15698/mic2019.03.672}, abstractNote={Pelvic inflammatory disease (PID) is a female upper genital tract inflammatory disorder that arises after sexually transmitted bacterial infections (STI). Factors modulating risk for reproductive sequelae include co-infection, microbiota, host genetics and physiology. In a pilot study of cervical samples obtained from women at high risk for STIs, we examined the potential for unbiased characterization of host, pathogen and microbiome interactions using whole transcriptome sequencing analysis of ribosomal RNA-depleted total RNAs (Total RNA-Seq). Only samples from women with STI infection contained pathogen-specific sequences (3 to 38% transcriptome coverage). Simultaneously, we identified and quantified their active microbial communities. After integration with host-derived reads from the same data, we detected clustering of host transcriptional profiles that reflected microbiome differences and STI infection. Together, our study suggests that total RNA profiling will advance understanding of the interplay of pathogen, host and microbiota during natural infection and may reveal novel, outcome-relevant biomarkers.}, number={3}, journal={MICROBIAL CELL}, author={Catherine M. O'Connell and Brochu, Hayden and Girardi, Jenna and Harrell, Erin and Jones, Aiden and Darville, Toni and Sena, Arlene C. and Peng, Xinxia}, year={2019}, month={Mar}, pages={177–183} } @article{martinez_fouda_peng_ackerman_permar_2018, title={Noncanonical placental Fc receptors: What is their role in modulating transplacental transfer of maternal IgG?}, volume={14}, ISSN={1553-7374}, url={http://dx.doi.org/10.1371/journal.ppat.1007161}, DOI={10.1371/journal.ppat.1007161}, abstractNote={The transplacental transfer of maternal Immunoglobulin G (IgG) to the fetus is critical for protection against infectious diseases in the first year of life [1]. Maternal protective IgG is transferred from the maternal to the fetal circulatory system via the placenta, and this process begins in the first trimester of pregnancy [2]. By 37–40 weeks of gestation, maternal passively acquired IgG concentrations in newborns can exceed maternal IgG serum levels in normal pregnancies [3–7]. Yet, the molecular mechanisms of transplacental transfer of maternal IgG remain poorly understood. In order to reach the fetal circulatory system, maternal IgG must traverse three distinct placental anatomical barriers: (1) the syncytiotrophoblast cell barrier, (2) the villous stroma containing placental fibroblasts and Hofbauer cells, and (3) fetal endothelial cells. It is well established that IgG crosses the syncytiotrophoblast by binding to the canonical IgG shuttle receptor: Fragment crystallizable (Fc) receptor neonatal (FcRn) [2, 8]. However, how maternal IgG traverses the subsequent placental barriers is not completely understood, as they do not express FcRn, yet recent RNAseq analyses have shown that Fcγ receptors, including FcγRIIIa, FcγRIIa, FcγRIIb, and FcγRI, are expressed in term placentas [9]. However, it should be cautioned that it is not yet known if these noncanonical placental FcRs play a role, if at all, in the transplacental transfer of maternal IgG. A deeper understanding of the molecular mechanism(s) of IgG binding to placentally expressed Fc receptors could be important (1) for the design of novel maternal IgG-based therapeutics and vaccines with optimal transplacental transfer efficiency, with the ultimate goal of increasing infant protection against congenital and neonatal infectious diseases, and (2) to optimize the Fc region of immunomodulatory IgG monoclonal antibody therapeutics for blunted transplacental transfer to potentially reduce the transplacental transport of maternal self-reactive IgG in women with autoimmune disorders.}, number={8}, journal={PLOS Pathogens}, publisher={Public Library of Science (PLoS)}, author={Martinez, David R. and Fouda, Genevieve G. and Peng, Xinxia and Ackerman, Margaret E. and Permar, Sallie R.}, editor={Sheppard, Donald C.Editor}, year={2018}, month={Aug}, pages={e1007161} } @misc{lemler_brochu_yang_harrell_peng_2017, title={Elucidating the role of host long non-coding RNA during viral infection: Challenges and paths forward}, volume={5}, number={4}, journal={Vaccines}, author={Lemler, D. J. and Brochu, H. N. and Yang, F. and Harrell, E. A. and Peng, X. X.}, year={2017} } @article{forero_fenstermacher_wohlgemuth_nishida_carter_smith_peng_hayes_francis_treanor_et al._2017, title={Evaluation of the innate immune responses to influenza and live-attenuated influenza vaccine infection in primary differentiated human nasal epithelial cells}, volume={35}, ISSN={0264-410X}, url={http://dx.doi.org/10.1016/j.vaccine.2017.09.058}, DOI={10.1016/j.vaccine.2017.09.058}, abstractNote={The host innate immune response to influenza virus is a key determinant of pathogenic outcomes and long-term protective immune responses against subsequent exposures. Here, we present a direct contrast of the host responses in primary differentiated human nasal epithelial cell (hNEC) cultures following infection with either a seasonal H3N2 influenza virus (WT) or the antigenically-matched live-attenuated vaccine (LAIV) strain. Comparison of the transcriptional profiles obtained 24 and 36 h post-infection showed that the magnitude of gene expression was greater in LAIV infected relative to that observed in WT infected hNEC cultures. Functional enrichment analysis revealed that the antiviral and inflammatory responses were largely driven by type III IFN induction in both WT and LAIV infected cells. However, the enrichment of biological pathways involved in the recruitment of mononuclear leukocytes, antigen-presenting cells, and T lymphocytes was uniquely observed in LAIV infected cells. These observations were reflective of the host innate immune responses observed in individuals acutely infected with influenza viruses. These findings indicate that cell-intrinsic type III IFN-mediated innate immune responses in the nasal epithelium are not only crucial for viral clearance and attenuation, but may also play an important role in the induction of protective immune responses with live-attenuated vaccines.}, number={45}, journal={Vaccine}, publisher={Elsevier BV}, author={Forero, Adriana and Fenstermacher, Katherine and Wohlgemuth, Nicholas and Nishida, Andrew and Carter, Victoria and Smith, Elise A. and Peng, Xinxia and Hayes, Melissa and Francis, Doreen and Treanor, John and et al.}, year={2017}, month={Oct}, pages={6112–6121} } @article{peng_li_gilbert_geraghty_katze_2016, title={FCGR2C Polymorphisms Associated with HIV-1 Vaccine Protection Are Linked to Altered Gene Expression of Fc-γ Receptors in Human B Cells}, volume={11}, ISSN={1932-6203}, url={http://dx.doi.org/10.1371/journal.pone.0152425}, DOI={10.1371/journal.pone.0152425}, abstractNote={The phase III Thai RV144 vaccine trial showed an estimated vaccine efficacy (VE) to prevent HIV-1 infection of 31.2%, which has motivated the search for immune correlates of vaccine protection. In a recent report, several single nucleotide polymorphisms (SNPs) in FCGR2C were identified to associate with the level of VE in the RV144 trial. To investigate the functional significance of these SNPs, we utilized a large scale B cell RNA sequencing database of 462 individuals from the 1000 Genomes Project to examine associations between FCGR2C SNPs and gene expression. We found that the FCGR2C SNPs that associated with vaccine efficacy in RV144 also strongly associated with the expression of FCGR2A/C and one of them also associated with the expression of Fc receptor-like A (FCRLA), another Fc-γ receptor (FcγR) gene that was not examined in the previous report. These results suggest that the expression of FcγR genes is influenced by these SNPs either directly or in linkage with other causal variants. More importantly, these results motivate further investigations into the potential for a causal association of expression and alternative splicing of FCGR2C and other FcγR genes with the HIV-1 vaccine protection in the RV144 trial and other similar studies.}, number={3}, journal={PLOS ONE}, publisher={Public Library of Science (PLoS)}, author={Peng, Xinxia and Li, Shuying S. and Gilbert, Peter B. and Geraghty, Daniel E. and Katze, Michael G.}, editor={Tang, JianmingEditor}, year={2016}, month={Mar}, pages={e0152425} } @article{tisoncik-go_gasper_kyle_eisfeld_selinger_hatta_morrison_korth_zink_kim_et al._2016, title={Integrated Omics Analysis of Pathogenic Host Responses during Pandemic H1N1 Influenza Virus Infection: The Crucial Role of Lipid Metabolism}, volume={19}, ISSN={1931-3128}, url={http://dx.doi.org/10.1016/j.chom.2016.01.002}, DOI={10.1016/j.chom.2016.01.002}, abstractNote={Pandemic influenza viruses modulate proinflammatory responses that can lead to immunopathogenesis. We present an extensive and systematic profiling of lipids, metabolites, and proteins in respiratory compartments of ferrets infected with either 1918 or 2009 human pandemic H1N1 influenza viruses. Integrative analysis of high-throughput omics data with virologic and histopathologic data uncovered relationships between host responses and phenotypic outcomes of viral infection. Proinflammatory lipid precursors in the trachea following 1918 infection correlated with severe tracheal lesions. Using an algorithm to infer cell quantity changes from gene expression data, we found enrichment of distinct T cell subpopulations in the trachea. There was also a predicted increase in inflammatory monocytes in the lung of 1918 virus-infected animals that was sustained throughout infection. This study presents a unique resource to the influenza research community and demonstrates the utility of an integrative systems approach for characterization of lipid metabolism alterations underlying respiratory responses to viruses.}, number={2}, journal={Cell Host & Microbe}, publisher={Elsevier BV}, author={Tisoncik-Go, Jennifer and Gasper, David J. and Kyle, Jennifer E. and Eisfeld, Amie J. and Selinger, Christian and Hatta, Masato and Morrison, Juliet and Korth, Marcus J. and Zink, Erika M. and Kim, Young-Mo and et al.}, year={2016}, month={Feb}, pages={254–266} } @article{peng_pyo_thomas_pyon_law_wang_geraghty_katze_2015, place={New Orleans}, title={Quantitative expression analysis of rhesus macaque MHC alleles}, volume={194}, number={113}, journal={Journal of Immunology}, author={Peng, X. and Pyo, C. and Thomas, M. and Pyon, Y. and Law, L. and Wang, R. and Geraghty, D. and Katze, M.}, year={2015} } @article{josset_tchitchek_gralinski_ferris_eisfeld_green_thomas_tisoncik-go_schroth_kawaoka_et al._2014, title={Annotation of long non-coding RNAs expressed in Collaborative Cross founder mice in response to respiratory virus infection reveals a new class of interferon-stimulated transcripts}, volume={11}, ISSN={1547-6286 1555-8584}, url={http://dx.doi.org/10.4161/rna.29442}, DOI={10.4161/rna.29442}, abstractNote={The outcome of respiratory virus infection is determined by a complex interplay of viral and host factors. Some potentially important host factors for the antiviral response, whose functions remain largely unexplored, are long non-coding RNAs (lncRNAs). Here we systematically inferred the regulatory functions of host lncRNAs in response to influenza A virus and severe acute respiratory syndrome coronavirus (SARS-CoV) based on their similarity in expression with genes of known function. We performed total RNA-Seq on viral-infected lungs from eight mouse strains, yielding a large data set of transcriptional responses. Overall 5,329 lncRNAs were differentially expressed after infection. Most of the lncRNAs were co-expressed with coding genes in modules enriched in genes associated with lung homeostasis pathways or immune response processes. Each lncRNA was further individually annotated using a rank-based method, enabling us to associate 5,295 lncRNAs to at least one gene set and to predict their potential cis effects. We validated the lncRNAs predicted to be interferon-stimulated by profiling mouse responses after interferon-α treatment. Altogether, these results provide a broad categorization of potential lncRNA functions and identify subsets of lncRNAs with likely key roles in respiratory virus pathogenesis. These data are fully accessible through the MOuse NOn-Code Lung interactive database (MONOCLdb).}, number={7}, journal={RNA Biology}, publisher={Informa UK Limited}, author={Josset, Laurence and Tchitchek, Nicolas and Gralinski, Lisa E and Ferris, Martin T and Eisfeld, Amie J and Green, Richard R and Thomas, Matthew J and Tisoncik-Go, Jennifer and Schroth, Gary P and Kawaoka, Yoshihiro and et al.}, year={2014}, month={Jun}, pages={875–890} } @article{peng_pipes_xiong_green_jones_ruzzo_schroth_mason_palermo_katze_2014, title={Assessment and improvement of Indian-origin rhesus macaque and Mauritian-origin cynomolgus macaque genome annotations using deep transcriptome sequencing data}, volume={43}, ISSN={0047-2565}, url={http://dx.doi.org/10.1111/jmp.12125}, DOI={10.1111/jmp.12125}, abstractNote={Abstract}, number={5}, journal={Journal of Medical Primatology}, publisher={Wiley}, author={Peng, Xinxia and Pipes, Lenore and Xiong, Hao and Green, Richard R. and Jones, Daniel C. and Ruzzo, Walter L. and Schroth, Gary P. and Mason, Christopher E. and Palermo, Robert E. and Katze, Michael G.}, year={2014}, month={May}, pages={317–328} } @article{peng_sova_green_thomas_korth_proll_xu_cheng_yi_chen_et al._2014, title={Deep Sequencing of HIV-Infected Cells: Insights into Nascent Transcription and Host-Directed Therapy}, volume={88}, ISSN={0022-538X 1098-5514}, url={http://dx.doi.org/10.1128/jvi.00768-14}, DOI={10.1128/jvi.00768-14}, abstractNote={ABSTRACT}, number={16}, journal={Journal of Virology}, publisher={American Society for Microbiology}, author={Peng, X. and Sova, P. and Green, R. R. and Thomas, M. J. and Korth, M. J. and Proll, S. and Xu, J. and Cheng, Y. and Yi, K. and Chen, L. and et al.}, year={2014}, month={May}, pages={8768–8782} } @article{barrenas_palermo_agricola_agy_aicher_carter_flanary_green_mclain_li_et al._2014, title={Deep Transcriptional Sequencing of Mucosal Challenge Compartment from Rhesus Macaques Acutely Infected with Simian Immunodeficiency Virus Implicates Loss of Cell Adhesion Preceding Immune Activation}, volume={88}, ISSN={0022-538X 1098-5514}, url={http://dx.doi.org/10.1128/jvi.00543-14}, DOI={10.1128/jvi.00543-14}, abstractNote={ABSTRACT}, number={14}, journal={Journal of Virology}, publisher={American Society for Microbiology}, author={Barrenas, Fredrik and Palermo, Robert E. and Agricola, Brian and Agy, Michael B. and Aicher, Lauri and Carter, Victoria and Flanary, Leon and Green, Richard R. and McLain, Randy and Li, Qingsheng and et al.}, editor={Silvestri, G.Editor}, year={2014}, month={May}, pages={7962–7972} } @article{xiong_morrison_ferris_gralinski_whitmore_green_thomas_tisoncik-go_schroth_pardo-manuel de villena_et al._2014, title={Genomic Profiling of Collaborative Cross Founder Mice Infected with Respiratory Viruses Reveals Novel Transcripts and Infection-Related Strain-Specific Gene and Isoform Expression}, volume={4}, ISSN={2160-1836}, url={http://dx.doi.org/10.1534/g3.114.011759}, DOI={10.1534/g3.114.011759}, abstractNote={Abstract}, number={8}, journal={G3: Genes|Genomes|Genetics}, publisher={Genetics Society of America}, author={Xiong, Hao and Morrison, Juliet and Ferris, Martin T. and Gralinski, Lisa E. and Whitmore, Alan C. and Green, Richard and Thomas, Matthew J. and Tisoncik-Go, Jennifer and Schroth, Gary P. and Pardo-Manuel de Villena, Fernando and et al.}, year={2014}, month={Jun}, pages={1429–1444} } @article{falzarano_de wit_feldmann_rasmussen_okumura_peng_thomas_van doremalen_haddock_nagy_et al._2014, title={Infection with MERS-CoV Causes Lethal Pneumonia in the Common Marmoset}, volume={10}, ISSN={1553-7374}, url={http://dx.doi.org/10.1371/journal.ppat.1004250}, DOI={10.1371/journal.ppat.1004250}, abstractNote={The availability of a robust disease model is essential for the development of countermeasures for Middle East respiratory syndrome coronavirus (MERS-CoV). While a rhesus macaque model of MERS-CoV has been established, the lack of uniform, severe disease in this model complicates the analysis of countermeasure studies. Modeling of the interaction between the MERS-CoV spike glycoprotein and its receptor dipeptidyl peptidase 4 predicted comparable interaction energies in common marmosets and humans. The suitability of the marmoset as a MERS-CoV model was tested by inoculation via combined intratracheal, intranasal, oral and ocular routes. Most of the marmosets developed a progressive severe pneumonia leading to euthanasia of some animals. Extensive lesions were evident in the lungs of all animals necropsied at different time points post inoculation. Some animals were also viremic; high viral loads were detected in the lungs of all infected animals, and total RNAseq demonstrated the induction of immune and inflammatory pathways. This is the first description of a severe, partially lethal, disease model of MERS-CoV, and as such will have a major impact on the ability to assess the efficacy of vaccines and treatment strategies as well as allowing more detailed pathogenesis studies.}, number={8}, journal={PLoS Pathogens}, publisher={Public Library of Science (PLoS)}, author={Falzarano, Darryl and de Wit, Emmie and Feldmann, Friederike and Rasmussen, Angela L. and Okumura, Atsushi and Peng, Xinxia and Thomas, Matthew J. and van Doremalen, Neeltje and Haddock, Elaine and Nagy, Lee and et al.}, editor={Denison, Mark R.Editor}, year={2014}, month={Aug}, pages={e1004250} } @article{peng_alföldi_gori_eisfeld_tyler_tisoncik-go_brawand_law_skunca_hatta_et al._2014, title={The draft genome sequence of the ferret (Mustela putorius furo) facilitates study of human respiratory disease}, volume={32}, ISSN={1087-0156 1546-1696}, url={http://dx.doi.org/10.1038/nbt.3079}, DOI={10.1038/nbt.3079}, abstractNote={The genome sequence of the ferret, a model of human respiratory disease, enables research on influenza and cystic fibrosis. The domestic ferret (Mustela putorius furo) is an important animal model for multiple human respiratory diseases. It is considered the 'gold standard' for modeling human influenza virus infection and transmission1,2,3,4. Here we describe the 2.41 Gb draft genome assembly of the domestic ferret, constituting 2.28 Gb of sequence plus gaps. We annotated 19,910 protein-coding genes on this assembly using RNA-seq data from 21 ferret tissues. We characterized the ferret host response to two influenza virus infections by RNA-seq analysis of 42 ferret samples from influenza time-course data and showed distinct signatures in ferret trachea and lung tissues specific to 1918 or 2009 human pandemic influenza virus infections. Using microarray data from 16 ferret samples reflecting cystic fibrosis disease progression, we showed that transcriptional changes in the CFTR-knockout ferret lung reflect pathways of early disease that cannot be readily studied in human infants with cystic fibrosis disease.}, number={12}, journal={Nature Biotechnology}, publisher={Springer Nature}, author={Peng, Xinxia and Alföldi, Jessica and Gori, Kevin and Eisfeld, Amie J and Tyler, Scott R and Tisoncik-Go, Jennifer and Brawand, David and Law, G Lynn and Skunca, Nives and Hatta, Masato and et al.}, year={2014}, month={Nov}, pages={1250–1255} } @article{peng_thierry-mieg_thierry-mieg_nishida_pipes_bozinoski_thomas_kelly_weiss_raveendran_et al._2014, title={Tissue-specific transcriptome sequencing analysis expands the non-human primate reference transcriptome resource (NHPRTR)}, volume={43}, ISSN={1362-4962 0305-1048}, url={http://dx.doi.org/10.1093/nar/gku1110}, DOI={10.1093/nar/gku1110}, abstractNote={The non-human primate reference transcriptome resource (NHPRTR, available online at http://nhprtr.org/) aims to generate comprehensive RNA-seq data from a wide variety of non-human primates (NHPs), from lemurs to hominids. In the 2012 Phase I of the NHPRTR project, 19 billion fragments or 3.8 terabases of transcriptome sequences were collected from pools of ∼20 tissues in 15 species and subspecies. Here we describe a major expansion of NHPRTR by adding 10.1 billion fragments of tissue-specific RNA-seq data. For this effort, we selected 11 of the original 15 NHP species and subspecies and constructed total RNA libraries for the same ∼15 tissues in each. The sequence quality is such that 88% of the reads align to human reference sequences, allowing us to compute the full list of expression abundance across all tissues for each species, using the reads mapped to human genes. This update also includes improved transcript annotations derived from RNA-seq data for rhesus and cynomolgus macaques, two of the most commonly used NHP models and additional RNA-seq data compiled from related projects. Together, these comprehensive reference transcriptomes from multiple primates serve as a valuable community resource for genome annotation, gene dynamics and comparative functional analysis.}, number={D1}, journal={Nucleic Acids Research}, publisher={Oxford University Press (OUP)}, author={Peng, Xinxia and Thierry-Mieg, Jean and Thierry-Mieg, Danielle and Nishida, Andrew and Pipes, Lenore and Bozinoski, Marjan and Thomas, Matthew J. and Kelly, Sara and Weiss, Jeffrey M. and Raveendran, Muthuswamy and et al.}, year={2014}, month={Nov}, pages={D737–D742} } @article{bruce_ryan_thomas_peng_grundhoff_tsai_rose_2013, title={Next-Generation Sequence Analysis of the Genome of RFHVMn, the Macaque Homolog of Kaposi's Sarcoma (KS)-Associated Herpesvirus, from a KS-Like Tumor of a Pig-Tailed Macaque}, volume={87}, ISSN={0022-538X}, url={http://dx.doi.org/10.1128/jvi.02331-13}, DOI={10.1128/jvi.02331-13}, abstractNote={ABSTRACT}, number={24}, journal={Journal of Virology}, publisher={American Society for Microbiology}, author={Bruce, A. G. and Ryan, J. T. and Thomas, M. J. and Peng, X. and Grundhoff, A. and Tsai, C.-C. and Rose, T. M.}, year={2013}, month={Oct}, pages={13676–13693} } @article{jones_ruzzo_peng_katze_2012, title={A new approach to bias correction in RNA-Seq}, volume={28}, ISSN={1460-2059 1367-4803}, url={http://dx.doi.org/10.1093/bioinformatics/bts055}, DOI={10.1093/bioinformatics/bts055}, abstractNote={Abstract}, number={7}, journal={Bioinformatics}, publisher={Oxford University Press (OUP)}, author={Jones, Daniel C. and Ruzzo, Walter L. and Peng, Xinxia and Katze, Michael G.}, year={2012}, month={Jan}, pages={921–928} } @article{jones_ruzzo_peng_katze_2012, title={Compression of next-generation sequencing reads aided by highly efficient de novo assembly}, volume={40}, ISSN={1362-4962 0305-1048}, url={http://dx.doi.org/10.1093/nar/gks754}, DOI={10.1093/nar/gks754}, abstractNote={We present Quip, a lossless compression algorithm for next-generation sequencing data in the FASTQ and SAM/BAM formats. In addition to implementing reference-based compression, we have developed, to our knowledge, the first assembly-based compressor, using a novel de novo assembly algorithm. A probabilistic data structure is used to dramatically reduce the memory required by traditional de Bruijn graph assemblers, allowing millions of reads to be assembled very efficiently. Read sequences are then stored as positions within the assembled contigs. This is combined with statistical compression of read identifiers, quality scores, alignment information and sequences, effectively collapsing very large data sets to <15% of their original size with no loss of information. Availability: Quip is freely available under the 3-clause BSD license from http://cs.washington.edu/homes/dcjones/quip.}, number={22}, journal={Nucleic Acids Research}, publisher={Oxford University Press (OUP)}, author={Jones, Daniel C. and Ruzzo, Walter L. and Peng, Xinxia and Katze, Michael G.}, year={2012}, month={Aug}, pages={e171–e171} } @article{pipes_li_bozinoski_palermo_peng_blood_kelly_weiss_thierry-mieg_thierry-mieg_et al._2012, title={The non-human primate reference transcriptome resource (NHPRTR) for comparative functional genomics}, volume={41}, ISSN={0305-1048 1362-4962}, url={http://dx.doi.org/10.1093/nar/gks1268}, DOI={10.1093/nar/gks1268}, abstractNote={RNA-based next-generation sequencing (RNA-Seq) provides a tremendous amount of new information regarding gene and transcript structure, expression and regulation. This is particularly true for non-coding RNAs where whole transcriptome analyses have revealed that the much of the genome is transcribed and that many non-coding transcripts have widespread functionality. However, uniform resources for raw, cleaned and processed RNA-Seq data are sparse for most organisms and this is especially true for non-human primates (NHPs). Here, we describe a large-scale RNA-Seq data and analysis infrastructure, the NHP reference transcriptome resource (http://nhprtr.org); it presently hosts data from12 species of primates, to be expanded to 15 species/subspecies spanning great apes, old world monkeys, new world monkeys and prosimians. Data are collected for each species using pools of RNA from comparable tissues. We provide data access in advance of its deposition at NCBI, as well as browsable tracks of alignments against the human genome using the UCSC genome browser. This resource will continue to host additional RNA-Seq data, alignments and assemblies as they are generated over the coming years and provide a key resource for the annotation of NHP genomes as well as informing primate studies on evolution, reproduction, infection, immunity and pharmacology.}, number={D1}, journal={Nucleic Acids Research}, publisher={Oxford University Press (OUP)}, author={Pipes, Lenore and Li, Sheng and Bozinoski, Marjan and Palermo, Robert and Peng, Xinxia and Blood, Phillip and Kelly, Sara and Weiss, Jeffrey M. and Thierry-Mieg, Jean and Thierry-Mieg, Danielle and et al.}, year={2012}, month={Nov}, pages={D906–D914} } @article{peng_gralinski_ferris_frieman_thomas_proll_korth_tisoncik_heise_luo_et al._2011, title={Integrative Deep Sequencing of the Mouse Lung Transcriptome Reveals Differential Expression of Diverse Classes of Small RNAs in Response to Respiratory Virus Infection}, volume={2}, ISSN={2150-7511}, url={http://dx.doi.org/10.1128/mbio.00198-11}, DOI={10.1128/mbio.00198-11}, abstractNote={ABSTRACT}, number={6}, journal={mBio}, publisher={American Society for Microbiology}, author={Peng, Xinxia and Gralinski, Lisa and Ferris, Martin T. and Frieman, Matthew B. and Thomas, Matthew J. and Proll, Sean and Korth, Marcus J. and Tisoncik, Jennifer R. and Heise, Mark and Luo, Shujun and et al.}, editor={Cullen, Bryan and Dermody, Terence S.Editors}, year={2011}, month={Nov} } @article{chang_sova_peng_weiss_law_palermo_katze_2011, title={Next-Generation Sequencing Reveals HIV-1-Mediated Suppression of T Cell Activation and RNA Processing and Regulation of Noncoding RNA Expression in a CD4+ T Cell Line}, volume={2}, ISSN={2150-7511}, url={http://dx.doi.org/10.1128/mbio.00134-11}, DOI={10.1128/mbio.00134-11}, abstractNote={ABSTRACT}, number={5}, journal={mBio}, publisher={American Society for Microbiology}, author={Chang, Stewart T. and Sova, Pavel and Peng, Xinxia and Weiss, Jeffrey and Law, G. Lynn and Palermo, Robert E. and Katze, Michael G.}, editor={Unutmaz, Derya and Dermody, Terence S.Editors}, year={2011}, month={Sep} } @article{cilloniz_pantin-jackwood_ni_goodman_peng_proll_carter_rosenzweig_szretter_katz_et al._2010, title={Lethal Dissemination of H5N1 Influenza Virus Is Associated with Dysregulation of Inflammation and Lipoxin Signaling in a Mouse Model of Infection}, volume={84}, ISSN={0022-538X}, url={http://dx.doi.org/10.1128/jvi.00553-10}, DOI={10.1128/jvi.00553-10}, abstractNote={ABSTRACT}, number={15}, journal={Journal of Virology}, publisher={American Society for Microbiology}, author={Cilloniz, C. and Pantin-Jackwood, M. J. and Ni, C. and Goodman, A. G. and Peng, X. and Proll, S. C. and Carter, V. S. and Rosenzweig, E. R. and Szretter, K. J. and Katz, J. M. and et al.}, year={2010}, month={May}, pages={7613–7624} } @article{li_chan_li_ni_peng_rosenzweig_tumpey_katze_2010, title={MicroRNA Expression and Virulence in Pandemic Influenza Virus-Infected Mice}, volume={84}, ISSN={0022-538X}, url={http://dx.doi.org/10.1128/jvi.02203-09}, DOI={10.1128/jvi.02203-09}, abstractNote={ABSTRACT}, number={6}, journal={Journal of Virology}, publisher={American Society for Microbiology}, author={Li, Y. and Chan, E. Y. and Li, J. and Ni, C. and Peng, X. and Rosenzweig, E. and Tumpey, T. M. and Katze, M. G.}, year={2010}, month={Jan}, pages={3023–3032} } @article{aly_lindner_mackellar_peng_kappe_2010, title={SAP1 is a critical post-transcriptional regulator of infectivity in malaria parasite sporozoite stages}, volume={79}, ISSN={0950-382X}, url={http://dx.doi.org/10.1111/j.1365-2958.2010.07497.x}, DOI={10.1111/j.1365-2958.2010.07497.x}, abstractNote={Summary}, number={4}, journal={Molecular Microbiology}, publisher={Wiley}, author={Aly, Ahmed S. I. and Lindner, Scott E. and MacKellar, Drew C. and Peng, Xinxia and Kappe, Stefan H. I.}, year={2010}, month={Dec}, pages={929–939} } @article{peng_gralinski_armour_ferris_thomas_proll_bradel-tretheway_korth_castle_biery_et al._2010, title={Unique Signatures of Long Noncoding RNA Expression in Response to Virus Infection and Altered Innate Immune Signaling}, volume={1}, ISSN={2150-7511}, url={http://dx.doi.org/10.1128/mbio.00206-10}, DOI={10.1128/mbio.00206-10}, abstractNote={ABSTRACT}, number={5}, journal={mBio}, publisher={American Society for Microbiology}, author={Peng, Xinxia and Gralinski, Lisa and Armour, Christopher D. and Ferris, Martin T. and Thomas, Matthew J. and Proll, Sean and Bradel-Tretheway, Birgit G. and Korth, Marcus J. and Castle, John C. and Biery, Matthew C. and et al.}, editor={Sonenberg, Nahum and Dermody, Terence S.Editors}, year={2010}, month={Oct} } @article{peng_li_walters_rosenzweig_lederer_aicher_proll_katze_2009, title={Computational identification of hepatitis C virus associated microRNA-mRNA regulatory modules in human livers}, volume={10}, ISSN={1471-2164}, url={http://dx.doi.org/10.1186/1471-2164-10-373}, DOI={10.1186/1471-2164-10-373}, abstractNote={Abstract}, number={1}, journal={BMC Genomics}, publisher={Springer Nature}, author={Peng, Xinxia and Li, Yu and Walters, Kathie-Anne and Rosenzweig, Elizabeth R and Lederer, Sharon L and Aicher, Lauri D and Proll, Sean and Katze, Michael G}, year={2009}, pages={373} } @article{albuquerque_carret_grosso_tarun_peng_kappe_prudêncio_mota_2009, title={Host cell transcriptional profiling during malaria liver stage infection reveals a coordinated and sequential set of biological events}, volume={10}, ISSN={1471-2164}, url={http://dx.doi.org/10.1186/1471-2164-10-270}, DOI={10.1186/1471-2164-10-270}, abstractNote={Abstract}, number={1}, journal={BMC Genomics}, publisher={Springer Nature}, author={Albuquerque, Sónia S and Carret, Céline and Grosso, Ana and Tarun, Alice S and Peng, Xinxia and Kappe, Stefan HI and Prudêncio, Miguel and Mota, Maria M}, year={2009}, pages={270} } @article{cillóniz_shinya_peng_korth_proll_aicher_carter_chang_kobasa_feldmann_et al._2009, title={Lethal Influenza Virus Infection in Macaques Is Associated with Early Dysregulation of Inflammatory Related Genes}, volume={5}, ISSN={1553-7374}, url={http://dx.doi.org/10.1371/journal.ppat.1000604}, DOI={10.1371/journal.ppat.1000604}, abstractNote={The enormous toll on human life during the 1918–1919 Spanish influenza pandemic is a constant reminder of the potential lethality of influenza viruses. With the declaration by the World Health Organization of a new H1N1 influenza virus pandemic, and with continued human cases of highly pathogenic H5N1 avian influenza virus infection, a better understanding of the host response to highly pathogenic influenza viruses is essential. To this end, we compared pathology and global gene expression profiles in bronchial tissue from macaques infected with either the reconstructed 1918 pandemic virus or the highly pathogenic avian H5N1 virus A/Vietnam/1203/04. Severe pathology was observed in respiratory tissues from 1918 virus-infected animals as early as 12 hours after infection, and pathology steadily increased at later time points. Although tissues from animals infected with A/Vietnam/1203/04 also showed clear signs of pathology early on, less pathology was observed at later time points, and there was evidence of tissue repair. Global transcriptional profiles revealed that specific groups of genes associated with inflammation and cell death were up-regulated in bronchial tissues from animals infected with the 1918 virus but down-regulated in animals infected with A/Vietnam/1203/04. Importantly, the 1918 virus up-regulated key components of the inflammasome, NLRP3 and IL-1β, whereas these genes were down-regulated by A/Vietnam/1203/04 early after infection. TUNEL assays revealed that both viruses elicited an apoptotic response in lungs and bronchi, although the response occurred earlier during 1918 virus infection. Our findings suggest that the severity of disease in 1918 virus-infected macaques is a consequence of the early up-regulation of cell death and inflammatory related genes, in which additive or synergistic effects likely dictate the severity of tissue damage.}, number={10}, journal={PLoS Pathogens}, publisher={Public Library of Science (PLoS)}, author={Cillóniz, Cristian and Shinya, Kyoko and Peng, Xinxia and Korth, Marcus J. and Proll, Sean C. and Aicher, Lauri D. and Carter, Victoria S. and Chang, Jean H. and Kobasa, Darwyn and Feldmann, Friedericke and et al.}, editor={Diamond, Michael S.Editor}, year={2009}, month={Oct}, pages={e1000604} } @article{goodman_fornek_medigeshi_perrone_peng_dyer_proll_knoblaugh_carter_korth_et al._2009, title={P58IPK: A Novel “CIHD” Member of the Host Innate Defense Response against Pathogenic Virus Infection}, volume={5}, ISSN={1553-7374}, url={http://dx.doi.org/10.1371/journal.ppat.1000438}, DOI={10.1371/journal.ppat.1000438}, abstractNote={To support their replication, viruses take advantage of numerous cellular factors and processes. Recent large-scale screens have identified hundreds of such factors, yet little is known about how viruses exploit any of these. Influenza virus infection post-translationally activates P58IPK, a cellular inhibitor of the interferon-induced, dsRNA-activated eIF2α kinase, PKR. Here, we report that infection of P58IPK knockout mice with influenza virus resulted in increased lung pathology, immune cell apoptosis, PKR activation, and mortality. Analysis of lung transcriptional profiles, including those induced by the reconstructed 1918 pandemic virus, revealed increased expression of genes associated with the cell death, immune, and inflammatory responses. These experiments represent the first use of a mammalian infection model to demonstrate the role of P58IPK in the antiviral response. Our results suggest that P58IPK represents a new class of molecule, a cellular inhibitor of the host defense (CIHD), as P58IPK is activated during virus infection to inhibit virus-induced apoptosis and inflammation to prolong host survival, even while prolonging viral replication.}, number={5}, journal={PLoS Pathogens}, publisher={Public Library of Science (PLoS)}, author={Goodman, Alan G. and Fornek, Jamie L. and Medigeshi, Guruprasad R. and Perrone, Lucy A. and Peng, Xinxia and Dyer, Matthew D. and Proll, Sean C. and Knoblaugh, Sue E. and Carter, Victoria S. and Korth, Marcus J. and et al.}, editor={Andino, RaulEditor}, year={2009}, month={May}, pages={e1000438} } @article{goodman_zeng_proll_peng_cilloniz_carter_korth_tumpey_katze_2009, title={The Alpha/Beta Interferon Receptor Provides Protection against Influenza Virus Replication but Is Dispensable for Inflammatory Response Signaling}, volume={84}, ISSN={0022-538X}, url={http://dx.doi.org/10.1128/jvi.01595-09}, DOI={10.1128/jvi.01595-09}, abstractNote={ABSTRACT}, number={4}, journal={Journal of Virology}, publisher={American Society for Microbiology}, author={Goodman, A. G. and Zeng, H. and Proll, S. C. and Peng, X. and Cilloniz, C. and Carter, V. S. and Korth, M. J. and Tumpey, T. M. and Katze, M. G.}, year={2009}, month={Nov}, pages={2027–2037} } @article{goodman_zeng_cilloniz_carter_peng_proll_tumpey_katze_2009, title={The Type I interferon receptor protects against influenza virus replication while the Type II receptor is dispensible}, volume={48}, ISSN={1043-4666}, url={http://dx.doi.org/10.1016/j.cyto.2009.07.294}, DOI={10.1016/j.cyto.2009.07.294}, number={1-2}, journal={Cytokine}, publisher={Elsevier BV}, author={Goodman, Alan G. and Zeng, Hui and Cilloniz, Cristian and Carter, Victoria S. and Peng, Xinxia and Proll, Sean C. and Tumpey, Terrence M. and Katze, Michael G.}, year={2009}, month={Oct}, pages={83} } @article{peng_chan_li_diamond_korth_katze_2009, title={Virus–host interactions: from systems biology to translational research}, volume={12}, ISSN={1369-5274}, url={http://dx.doi.org/10.1016/j.mib.2009.06.003}, DOI={10.1016/j.mib.2009.06.003}, abstractNote={Research embracing systems biology approaches and careful analysis of the critical host response has greatly expanded our understanding of infectious diseases. First-generation studies based on genomics and proteomics have made significant progress in establishing the foundation for network-based investigations on virus-host interactions. More recently, data from complementary high-throughput technologies, such as siRNA and microRNA screens and next-generation sequencing, are augmenting systems level analyses and are providing a more detailed and insightful multidimensional view of virus-host networks. Together with advances in data integration, systems biology approaches now have the potential to provide profound impacts on translational research, leading to the more rapid development of new therapeutics and vaccines for infectious diseases. In this review, we highlight new high-throughput technologies, a new philosophy for studying virus-host interactions, and discuss the potential of systems biology to facilitate bench-to-bedside research and create novel strategies to combat disease. Can we save the world using these approaches? Read on.}, number={4}, journal={Current Opinion in Microbiology}, publisher={Elsevier BV}, author={Peng, Xinxia and Chan, Eric Y and Li, Yu and Diamond, Deborah L and Korth, Marcus J and Katze, Michael G}, year={2009}, month={Aug}, pages={432–438} } @article{tarun_peng_dumpit_ogata_silva-rivera_camargo_daly_bergman_kappe_2008, title={A combined transcriptome and proteome survey of malaria parasite liver stages}, volume={105}, ISSN={0027-8424 1091-6490}, url={http://dx.doi.org/10.1073/pnas.0710780104}, DOI={10.1073/pnas.0710780104}, abstractNote={ For 50 years since their discovery, the malaria parasite liver stages (LS) have been difficult to analyze, impeding their utilization as a critical target for antiinfection vaccines and drugs. We have undertaken a comprehensive transcriptome analysis in combination with a proteomic survey of LS. Green fluorescent protein-tagged Plasmodium yoelii (PyGFP) was used to efficiently isolate LS-infected hepatocytes from the rodent host. Genome-wide LS gene expression was profiled and compared with other parasite life cycle stages. The analysis revealed ≈2,000 genes active during LS development, and proteomic analysis identified 816 proteins. A subset of proteins appeared to be expressed in LS only. The data revealed exported parasite proteins and LS metabolic pathways including expression of FASII pathway enzymes. The FASII inhibitor hexachlorophene and the antibiotics, tetracycline and rifampicin, that target the apicoplast inhibited LS development, identifying FASII and other pathways localized in the apicoplast as potential drug targets to prevent malaria infection. }, number={1}, journal={Proceedings of the National Academy of Sciences}, publisher={Proceedings of the National Academy of Sciences}, author={Tarun, A. S. and Peng, X. and Dumpit, R. F. and Ogata, Y. and Silva-Rivera, H. and Camargo, N. and Daly, T. M. and Bergman, L. W. and Kappe, S. H. I.}, year={2008}, month={Jan}, pages={305–310} } @article{vaughan_chiu_ramasamy_li_gardner_tarun_kappe_peng_2008, title={Assessment and improvement of the Plasmodium yoelii yoelii genome annotation through comparative analysis}, volume={24}, ISSN={1460-2059 1367-4803}, url={http://dx.doi.org/10.1093/bioinformatics/btn140}, DOI={10.1093/bioinformatics/btn140}, abstractNote={Abstract}, number={13}, journal={Bioinformatics}, publisher={Oxford University Press (OUP)}, author={Vaughan, Ashley and Chiu, Sum-Ying and Ramasamy, Gowthaman and Li, Ling and Gardner, Malcolm J. and Tarun, Alice S. and Kappe, Stefan H.I. and Peng, Xinxia}, year={2008}, month={Jul}, pages={i383–i389} } @article{mikolajczak_silva-rivera_peng_tarun_camargo_jacobs-lorena_daly_bergman_de la vega_williams_et al._2008, title={Distinct Malaria Parasite Sporozoites Reveal Transcriptional Changes That Cause Differential Tissue Infection Competence in the Mosquito Vector and Mammalian Host}, volume={28}, ISSN={0270-7306}, url={http://dx.doi.org/10.1128/mcb.00553-08}, DOI={10.1128/mcb.00553-08}, abstractNote={ABSTRACT The malaria parasite sporozoite transmission stage develops and differentiates within parasite oocysts on the Anopheles mosquito midgut. Successful inoculation of the parasite into a mammalian host is critically dependent on the sporozoite's ability to first infect the mosquito salivary glands. Remarkable changes in tissue infection competence are observed as the sporozoites transit from the midgut oocysts to the salivary glands. Our microarray analysis shows that compared to oocyst sporozoites, salivary gland sporozoites upregulate expression of at least 124 unique genes. Conversely, oocyst sporozoites show upregulation of at least 47 genes (upregulated in oocyst sporozoites [UOS genes]) before they infect the salivary glands. Targeted gene deletion of UOS3, encoding a putative transmembrane protein with a thrombospondin repeat that localizes to the sporozoite secretory organelles, rendered oocyst sporozoites unable to infect the mosquito salivary glands but maintained the parasites' liver infection competence. This phenotype demonstrates the significance of differential UOS expression. Thus, the UIS-UOS gene classification provides a framework to elucidate the infectivity and transmission success of Plasmodium sporozoites on a whole-genome scale. Genes identified herein might represent targets for vector-based transmission blocking strategies (UOS genes), as well as strategies that prevent mammalian host infection (UIS genes).}, number={20}, journal={Molecular and Cellular Biology}, publisher={American Society for Microbiology}, author={Mikolajczak, S. A. and Silva-Rivera, H. and Peng, X. and Tarun, A. S. and Camargo, N. and Jacobs-Lorena, V. and Daly, T. M. and Bergman, L. W. and de la Vega, P. and Williams, J. and et al.}, year={2008}, month={Aug}, pages={6196–6207} } @inbook{peng_langston_saxton_baldwin_snoddy_2007, title={Detecting Network Motifs in Gene Co-expression Networks Through Integration of Protein Domain Information}, ISBN={9780387345680}, url={http://dx.doi.org/10.1007/978-0-387-34569-7_7}, DOI={10.1007/978-0-387-34569-7_7}, booktitle={Methods of Microarray Data Analysis V}, publisher={Springer US}, author={Peng, Xinxia and Langston, Michael A. and Saxton, Arnold M. and Baldwin, Nicole E. and Snoddy, Jay R.}, year={2007}, month={Feb}, pages={89–102} } @article{kirov_peng_baker_schmoyer_zhang_snoddy_2005, title={GeneKeyDB: A lightweight, gene-centric, relational database to support data mining environments}, volume={6}, ISSN={1471-2105}, url={http://dx.doi.org/10.1186/1471-2105-6-72}, DOI={10.1186/1471-2105-6-72}, abstractNote={The analysis of biological data is greatly enhanced by existing or emerging databases. Most existing databases, with few exceptions are not designed to easily support large scale computational analysis, but rather offer exclusively a web interface to the resource. We have recognized the growing need for a database which can be used successfully as a backend to computational analysis tools and pipelines. Such database should be sufficiently versatile to allow easy system integration. GeneKeyDB is a gene-centered relational database developed to enhance data mining in biological data sets. The system provides an underlying data layer for computational analysis tools and visualization tools. GeneKeyDB relies primarily on existing database identifiers derived from community databases (NCBI, GO, Ensembl, et al.) as well as the known relationships among those identifiers. It is a lightweight, portable, and extensible platform for integration with computational tools and analysis environments. GeneKeyDB can enable analysis tools and users to manipulate the intersections, unions, and differences among different data sets.}, number={1}, journal={BMC Bioinformatics}, publisher={Springer Nature}, author={Kirov, SA and Peng, X and Baker, E and Schmoyer, D and Zhang, B and Snoddy, J}, year={2005}, pages={72} }