Placenta-Specific Genes, Their Regulation During Villous Trophoblast Differentiation and Dysregulation in Preterm Preeclampsia.

The human placenta maintains pregnancy and supports the developing fetus by providing nutrition, gas-waste exchange, hormonal regulation, and an immunological barrier from the maternal immune system. The villous syncytiotrophoblast carries most of these functions and provides the interface between the maternal and fetal circulatory systems. The syncytiotrophoblast is generated by the biochemical and morphological differentiation of underlying cytotrophoblast progenitor cells.

Integrated Systems Biology Approach Identifies Novel Maternal and Placental Pathways of Preeclampsia.

Preeclampsia is a disease of the mother, fetus, and placenta, and the gaps in our understanding of the complex interactions among their respective disease pathways preclude successful treatment and prevention. The placenta has a key role in the pathogenesis of the terminal pathway characterized by exaggerated maternal systemic inflammation, generalized endothelial damage, hypertension, and proteinuria. This of preeclampsia may be triggered by distinct underlying mechanisms that occur at early stages of pregnancy and induce different phenotypes.

Longitudinal Changes in Placental Magnetic Resonance Imaging Relaxation Parameter in Murine Pregnancy: Compartmental Analysis.

Objective: To quantify gestation-dependent longitudinal changes in the magnetic resonance transverse relaxation time (T2) parameter of the major constituent regions of the mouse placenta and to evaluate their relative contributions to changes in overall placental T2.

Methods: Timed-pregnant CD-1 mice underwent magnetic resonance imaging at 7.0 T field strength, on gestational day 13 (GD13), GD15 and GD17.

Down-weighting overlapping genes improves gene set analysis.

Background: The identification of gene sets that are significantly impacted in a given condition based on microarray data is a crucial step in current life science research. Most gene set analysis methods treat genes equally, regardless how specific they are to a given gene set.

Results: In this work we propose a new gene set analysis method that computes a gene set score as the mean of absolute values of weighted moderated gene t-scores.

Developing classifiers for the detection of cancer using multi-analytes.

The development of a successful classifier from multiple predictors (analytes) is a multistage process complicated typically by the paucity of the data samples when compared to the number of available predictors. Choosing an adequate validation strategy is key for drawing sound conclusions about the usefulness of the classifier. Other important decisions have to be made regarding the type of prediction model to be used and training algorithm, as well as the way in which the markers are selected.

A novel signaling pathway impact analysis.

Motivation: Gene expression class comparison studies may identify hundreds or thousands of genes as differentially expressed (DE) between sample groups. Gaining biological insight from the result of such experiments can be approached, for instance, by identifying the signaling pathways impacted by the observed changes. Most of the existing pathway analysis methods focus on either the number of DE genes observed in a given pathway (enrichment analysis methods), or on the correlation between the pathway genes and the class of the samples (functional class scoring methods).

Whole-genome microarray and targeted analysis of angiogenesis-regulating gene expression (ENG, FLT1, VEGF, PlGF) in placentas from pre-eclamptic and small-for-gestational-age pregnancies.

Objective: To compare the placental pathology associated with pre-eclampsia (PE) and/or fetal growth restriction, the transcriptomes of placental tissues from PE and small-for-gestational-age (SGA) pregnancies were explored. In addition, a targeted analysis of angiogenesis-regulating gene expression was performed.

Methods: Whole-genome microarray analysis was performed on placental tissue from gestational age-matched PE (n = 10), SGA (n = 8) and PE + SGA (n = 10) pregnancies.

Gene expression profiling demonstrates a novel role for foetal fibrocytes and the umbilical vessels in human fetoplacental development.

There is a difference in the susceptibility to inflammation between the umbilical vein (UV) and the umbilical arteries (UAs). This led us to hypothesize that there is an intrinsic difference in the pro-inflammatory response between UA and UV. Real-time quantitative RT-PCR and microarray analysis revealed higher expression of interleukin (IL)-1beta and IL-8 mRNA in the UV and differential expression of 567 genes between the UA and UV associated with distinct biological processes, including the immune response.

A systems biology approach for pathway level analysis.

A common challenge in the analysis of genomics data is trying to understand the underlying phenomenon in the context of all complex interactions taking place on various signaling pathways. A statistical approach using various models is universally used to identify the most relevant pathways in a given experiment. Here, we show that the existing pathway analysis methods fail to take into consideration important biological aspects and may provide incorrect results in certain situations.