Wenying Pan1, Thuy T M Ngo1, Joan Camunas-Soler1, Chun-Xiao Song1, Mark Kowarsky1, Yair J Blumenfeld2, Ronald J Wong3,4, Gary M Shaw3,4, David K Stevenson3,4, Stephen R Quake5. 1. Departments of Bioengineering and Applied Physics, Stanford University, and Chan Zuckerberg Biohub, Stanford, CA. 2. Division of Maternal-Fetal Medicine, Department of Obstetrics and Gynecology, Stanford University, Stanford, CA. 3. March of Dimes Prematurity Research Center, Stanford University School of Medicine, Stanford, CA. 4. Department of Pediatrics, Stanford University School of Medicine, Stanford, CA. 5. Departments of Bioengineering and Applied Physics, Stanford University, and Chan Zuckerberg Biohub, Stanford, CA; quake@stanford.edu.
Abstract
BACKGROUND: Plasma cell-free RNA (cfRNA) encompasses a broad spectrum of RNA species that can be derived from both human cells and microbes. Because cfRNA is fragmented and of low concentration, it has been challenging to profile its transcriptome using standard RNA-seq methods. METHODS: We assessed several recently developed RNA-seq methods on cfRNA samples. We then analyzed the dynamic changes of both the human transcriptome and the microbiome of plasma during pregnancy from 60 women. RESULTS: cfRNA reflects a well-orchestrated immune modulation during pregnancy: an up-regulation of antiinflammatory genes and an increased abundance of antimicrobial genes. We observed that the plasma microbiome remained relatively stable during pregnancy. The bacteria Ureaplasma shows an increased prevalence and increased abundance at postpartum, which is likely to be associated with postpartum infection. We demonstrated that cfRNA-seq can be used to monitor viral infections. We detected a number of human pathogens in our patients, including an undiagnosed patient with a high load of human parvovirus B19 virus (B19V), which is known to be a potential cause of complications in pregnancy. CONCLUSIONS: Plasma cfRNA-seq demonstrates the potential to simultaneously monitor immune response and microbial infections during pregnancy.
BACKGROUND: Plasma cell-free RNA (cfRNA) encompasses a broad spectrum of RNA species that can be derived from both human cells and microbes. Because cfRNA is fragmented and of low concentration, it has been challenging to profile its transcriptome using standard RNA-seq methods. METHODS: We assessed several recently developed RNA-seq methods on cfRNA samples. We then analyzed the dynamic changes of both the human transcriptome and the microbiome of plasma during pregnancy from 60 women. RESULTS: cfRNA reflects a well-orchestrated immune modulation during pregnancy: an up-regulation of antiinflammatory genes and an increased abundance of antimicrobial genes. We observed that the plasma microbiome remained relatively stable during pregnancy. The bacteria Ureaplasma shows an increased prevalence and increased abundance at postpartum, which is likely to be associated with postpartum infection. We demonstrated that cfRNA-seq can be used to monitor viral infections. We detected a number of human pathogens in our patients, including an undiagnosed patient with a high load of humanparvovirus B19 virus (B19V), which is known to be a potential cause of complications in pregnancy. CONCLUSIONS: Plasma cfRNA-seq demonstrates the potential to simultaneously monitor immune response and microbial infections during pregnancy.
Authors: David K Stevenson; Ronald J Wong; Nima Aghaeepour; Ivana Maric; Martin S Angst; Kevin Contrepois; Gary L Darmstadt; Maurice L Druzin; Michael L Eisenberg; Brice Gaudilliere; Ronald S Gibbs; Ian H Gotlib; Jeffrey B Gould; Henry C Lee; Xuefeng B Ling; Jonathan A Mayo; Mira N Moufarrej; Cecele C Quaintance; Stephen R Quake; David A Relman; Marina Sirota; Michael P Snyder; Karl G Sylvester; Shiying Hao; Paul H Wise; Gary M Shaw; Michael Katz Journal: Pediatr Res Date: 2020-05-26 Impact factor: 3.756
Authors: David K Stevenson; Nima Aghaeepour; Ivana Maric; Martin S Angst; Gary L Darmstadt; Maurice L Druzin; Brice Gaudilliere; Xuefeng B Ling; Mira N Moufarrej; Laura S Peterson; Stephen R Quake; David A Relman; Michael P Snyder; Karl G Sylvester; Gary M Shaw; Ronald J Wong Journal: Semin Perinatol Date: 2021-03-24 Impact factor: 3.311
Authors: Mohammad Sajjad Ghaemi; Daniel B DiGiulio; Kévin Contrepois; Benjamin Callahan; Thuy T M Ngo; Brittany Lee-McMullen; Benoit Lehallier; Anna Robaczewska; David Mcilwain; Yael Rosenberg-Hasson; Ronald J Wong; Cecele Quaintance; Anthony Culos; Natalie Stanley; Athena Tanada; Amy Tsai; Dyani Gaudilliere; Edward Ganio; Xiaoyuan Han; Kazuo Ando; Leslie McNeil; Martha Tingle; Paul Wise; Ivana Maric; Marina Sirota; Tony Wyss-Coray; Virginia D Winn; Maurice L Druzin; Ronald Gibbs; Gary L Darmstadt; David B Lewis; Vahid Partovi Nia; Bruno Agard; Robert Tibshirani; Garry Nolan; Michael P Snyder; David A Relman; Stephen R Quake; Gary M Shaw; David K Stevenson; Martin S Angst; Brice Gaudilliere; Nima Aghaeepour Journal: Bioinformatics Date: 2019-01-01 Impact factor: 6.937
Authors: Marina Sirota; Cristel G Thomas; Rebecca Liu; Maya Zuhl; Payal Banerjee; Ronald J Wong; Cecele C Quaintance; Rita Leite; Jessica Chubiz; Rebecca Anderson; Joanne Chappell; Mara Kim; William Grobman; Ge Zhang; Antonis Rokas; Sarah K England; Samuel Parry; Gary M Shaw; Joe Leigh Simpson; Elizabeth Thomson; Atul J Butte Journal: Sci Data Date: 2018-11-06 Impact factor: 6.444