No abstract

BackgroundNovel high-resolution tools for pregnancy monitoring, including early detection of prenatal disorders, are needed. Changes in circulating microRNAs (c-miRNAs) during pregnancy could potentially inform about the functional status of the mother, the placenta and/or the fetus. However, whether c-miRNA profiles actually reflect distinct pregnancy-specific events at all stages remains unclear.MethodsLongitudinal large-scale RNAseq c-miRNA profiles at early, middle and late pregnancy, and after birth derived from eight women with healthy term pregnancies (n = 32 plasma samples) were compared against corresponding circulating profiles derived from age-matched non-pregnant women (n = 10). Data of fetal sex and growth indicators obtained during pregnancy evolution of the same women, were used to identify specific c-miRNA correlates in circulation.Results1449 c-miRNAs were detected in circulation in both pregnant and non-pregnant women with only 48 c-miRNAs differentially expressed relative to non-pregnant controls in at least one of the four studied stages (FDR < 0.05). Surprisingly, c-miRNA subpopulations with reported prominent expression in various pregnancy-associated compartments (placenta, amniotic fluid, umbilical cord plasma and breast milk) were found collectively under-expressed in maternal circulation throughout pregnancy (p < 0.05). Furthermore, we found a bias in global miRNAs expression in direct association with fetal sex right from the first trimester, in addition to a specific c-miRNA signature of fetal growth (R = 0.7, p < 0.01).ConclusionOur results demonstrate the existence of temporal changes in c-miRNAs populations associated to distinct aspects of pregnancy, including correlates of placental function and lactation, as well as fetal gender and growth, revealing a wider potential of c-miRNAs as biomarkers of specific aspects of maternal health and fetal growth.

Background: Novel high-resolution tools for pregnancy monitoring, including early detection of prenatal disorders, are needed. Changes in circulating microRNAs (c-miRNAs) during pregnancy could potentially inform about the functional status of the mother, the placenta and/or the fetus. However, whether c-miRNA profiles actually reflect distinct pregnancy-specific events at all stages remains unclear.Methods: Longitudinal large-scale RNAseq c-miRNA profiles at early, middle and late pregnancy, and after birth derived from eight women with healthy term pregnancies (n=32 plasma samples) were compared against corresponding circulating profiles derived from age-matched non-pregnant women (n=10). Data of fetal sex and growth indicators obtained during pregnancy evolution of the same women, were used to identify specific c-miRNA correlates in circulation.Results: 1449 c-miRNAs were detected in circulation in both pregnant and non-pregnant women with only 48 c-miRNAs differentially expressed relative to non-pregnant controls in at least one of the four studied stages (FDR<0.05). Surprisingly, c-miRNA subpopulations with reported prominent expression in various pregnancy-associated compartments (placenta, amniotic fluid, umbilical cord plasma and breast milk) were found collectively under-expressed in maternal circulation throughout pregnancy (p<0.05). Furthermore, we found a bias in global miRNAs expression in direct association with fetal sex right from the first trimester, in addition to a specific c-miRNA signature of fetal growth (R = 0.7, p < 0.01).Conclusion: Our results demonstrate the existence of temporal changes in c-miRNAs populations associated to distinct aspects of pregnancy, including correlates of placental function and lactation, as well as fetal gender and growth, revealing a wider potential of c-miRNAs as biomarkers of specific aspects of maternal health and fetal growth.

The performance of local and global alignment algorithms circumscribe the alignment of sequences shorter than 30 nucleotides. Regardless of the computational approach applied, a series of diverse limitations accumulate as the length and similarity between the aligned sequences decreases, often resulting in alignment biases: local alignments have difficulties reporting correctly the number of matches and mismatches (m/mm) flanking the seed; global alignments lengthen the total alignment size and introduce gaps artificially. These biases compromise the accuracy of computational analysis of short sequences. Here we report ExtendAlign, a computational tool that overhauls and corrects the aforementioned bias generated by local and global alignments. ExtendAlign provides an end-to-end report of the accurate number of m/mm for all the nucleotides that flank a local alignment of short sequences, thus eliminating the artificial lengthening of the query size, the introduction of gaps, and the failure in reporting flanking m/mm. Since ExtendAlign combines the refinement and strength of global and local multiple sequence alignments, it delivers exceptional accuracy in correcting the alignment of dissimilar sequences in the range of ~35-50% similarity -also known as the twilight zone; indicating it can be adopted regularly whenever high accuracy is required for short-sequence alignments.