Noninvasive blood tests for fetal development predict gestational age and preterm delivery

Ngo, Thuy; Moufarrej, Mira N.; Rasmussen, Marie Louise H.; Camunas-Soler, Joan; Pan, Wenying; Okamoto, Jennifer; Neff, Norma; Liu, Keli; Wong, Ronald J.; Downes, Katheryne; Tibshirani, Robert; Shaw, Gary M.; Skotte, Line; Stevenson, David K.; Biggio, Joseph; Elovitz, Michal A.; Melbye, Mads; Quake, Stephen R.

doi:10.1126/science.aar3819

Cited by 216 publications

(258 citation statements)

References 36 publications

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“…Recent developments in noninvasive prenatal testing (NIPT) have revolutionized prenatal care. Recent reports suggest that this field may evolve to enable noninvasive prenatal transcriptomic and epigenomic profiling in utero . This is an extremely exciting concept because it may enable noninvasive monitoring for the detection and management of complex diseases of pregnancy such as preeclampsia and growth restriction.…”

Section: Introductionmentioning

confidence: 99%

High‐resolution analysis of the human placental DNA methylome in early gestation

et al. 2020

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Background/Objective We communicate high‐read‐depth bisulfite sequencing analysis of the chorionic villus (CV) DNA methylome from samples obtained between 11 and 13 weeks gestation and samples of gestationally age‐matched maternal blood cells (MBC). Methods This was achieved through solution‐phase targeted region capture (84 Mb) of bisulfite converted human DNA. Results We identified biphasic distribution of methylation in CV and MBC genomes. We found greater numbers of intermediate methylated sites (20%‐80% methylated) in CV and greater number of high methylation sites in MBC and investigated distributions of these in promoters, introns, exons, CpG islands, CpG islands shores, and enhancers. We identified differentially methylated sites distinguishing CV and MBC. These are less likely to occur in CpG islands (CGIs), particularly those that exist outside promoters, exons, and introns. We found that gene promoter and gene body methylation patterns are associated with mRNA transcriptional profiles in CV. Despite the relative hypomethylation of CV genomes, we found that these contain DM regions that are more likely to be hypermethylated in CV relative to MBC. Conclusions Our data provide novel insight into the structure and organization of the CV epigenome, which may inform future studies of placental biology and noninvasive prenatal phenotyping.

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Section: Introductionmentioning

confidence: 99%

High‐resolution analysis of the human placental DNA methylome in early gestation

et al. 2020

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“…Protein coding gene such as CGA, CSH1 and CSH2, and long non-coding gene such as PLAC4 15 , were very low or undetected in nonpregnant females, and increased during pregnancy. S100A8 which are related to pregnant immunomodulation 15 , also increased ( Fig. 5c).…”

Section: Palm-seq Was a Robust Methods For Plasma Rna-seqmentioning

confidence: 80%

“…Although the kits designed for total RNA such as Ribo-Zero Gold Kit NuGen's 13 or RNA-Seq Ovation System Kit 14 , were used before, they are not proper for cell-free RNA. Now, Small RNA Seq, SMARTer Seq and ScriptSeq are considered as optimized choices 15,[22][23][24] . However, Small RNA Seq method requires 5' phosphorylated and 3' hydroxyl 36…”

Section: Discussionmentioning

confidence: 99%

“…To assess the performance of different treatments and methods, we analyzed the data to account for differences in number of different genes detected and contribution of different kinds of RNA. PALM-Seq with PNKT (TD or no TD) could detect larger number of mRNA To further qualify our method, we referred to public data produced by SMARTer Seq (by using Clontech SMARTer Stranded Total RNA-Seq Kit -Pico) 15 , ScriptSeq (by using Illumina ScriptSeq v2 Kit) 23 and Small RNA Seq (by using NEBNext Small RNA Library Preparation Kit) 24 to quantify if PALM-seq was comparable or even better. While SMARTer Seq and ScriptSeq were designed for large fragment RNA, they were effective to detect mRNA or lncRNA ( Fig.…”

Section: Principle Of Palm-seqmentioning

confidence: 99%

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PALM-Seq: integrated sequencing of cell-free long RNA and small RNA

Yang

Wang

Zhu

et al. 2019

Preprint

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Cell-free RNA, including both long RNA and small RNA, has been considered important for its biological functions and potential clinical usage, but the major challenge is to effectively sequence them at the same time. Here we present PolyAdenylation Ligation Mediated-Seq (PALM-Seq), an integrated sequencing method for cell-free long and small RNA. Through terminal modification and addition of 3' polyadenylation and 5' adaptor, we could get mRNA, long non-coding RNA, microRNA, tRNA, piRNA and other RNAs in a single library. With target RNA depletion, all these RNAs could be sequenced with relatively low depth. Using PALM-Seq, we identified pregnant-related mRNAs, long non-coding RNAs and microRNAs in female plasma. We also applied PALM-Seq to sequence RNA from amniotic fluids, leukocytes and placentas, and could find RNA signatures associated with specific sample type. PALM-Seq provides an integrated, cost-effective and simple method to characterize the landscape of cell-free RNA, and can stimulate further progress in cell-free RNA study and usage.

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“…Our work demonstrates that machine learning algorithms applied to quantitative miRNA expression estimates also detect changes related to the cell type composition of tissues, such as the shift in hematopoietic cell abundance in the postnatal compared to the fetal liver. Given the emerging evidence of ncRNA stability in the blood and its rapid propagation throughout the body within extracellular vesicles (Bhome et al, 2018), we anticipate that the current space of markers used to non-invasively monitor development (Ngo et al, 2018) could be further expanded to small ncRNA.…”

Section: Discussionmentioning

confidence: 99%

A mouse tissue atlas of small non-coding RNA

Isakova

Quake

2018

Preprint

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Small non-coding RNAs (ncRNAs) play a vital role in a broad range of biological processes both in health and disease. A comprehensive quantitative reference of small ncRNA expression would significantly advance our understanding of ncRNA roles in shaping tissue functions.Here, we systematically profiled the levels of five ncRNA classes (miRNA, snoRNA, snRNA, scaRNA and tRNA fragments) across eleven mouse tissues by deep sequencing. Using fourteen biological replicates spanning both sexes, we identified that ~ 30% of small ncRNAs are distributed across the body in a tissue-specific manner with some are also being sexually dimorphic. We found that miRNAs are subject to "arm switching" between healthy tissues and that tRNA fragments are retained within tissues in both a gene-and a tissue-specific manner.Out of eleven profiled tissues we confirmed that brain contains the largest number of unique small ncRNA transcripts, some of which were previously annotated while others are identified for the first time in this study. Furthermore, by combining these findings with single-cell ATACseq data, we were able to connect identified brain-specific ncRNA with their cell types of origin.These results yield the most comprehensive characterization of specific and ubiquitous small RNAs in individual murine tissues to date, and we expect that this data will be a resource for the further identification of ncRNAs involved in tissue-function in health and dysfunction in disease.

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Noninvasive blood tests for fetal development predict gestational age and preterm delivery

Cited by 216 publications

References 36 publications

High‐resolution analysis of the human placental DNA methylome in early gestation

High‐resolution analysis of the human placental DNA methylome in early gestation

PALM-Seq: integrated sequencing of cell-free long RNA and small RNA

A mouse tissue atlas of small non-coding RNA

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