Ina Jungersen Andresen

• Andresen, Ina Jungersen; Romero, Roberto; Westerberg, Ane C.; Than, Nándor Gábor; Gomez-Lopez, Nardhy & Bhatti, Gaurav [Show all 14 contributors for this article] (2025). Large-Scale Proteomics Reveals New Candidate Biomarkers for Late-Onset Preeclampsia. Hypertension. ISSN 0194-911X. 83(2). doi: 10.1161/hypertensionaha.125.25189. Full text in Research Archive Show summary

  BACKGROUND: Preeclampsia is classified as either a more severe early onset or a more prevalent late-onset form. Lower PlGF (placental growth factor) and increased sFlt-1 (fms-like tyrosine kinase-1) in maternal circulation are promising biomarkers, yet they lack specificity for preeclampsia. METHODS: We quantified ≈7000 proteins in 673 samples collected from 89 patients with late-onset preeclampsia and 91 controls at T1 (15–22), T2 (22–30), and T3 (30–42) weeks. Elastic net and random forest models were fitted and evaluated by cross-validation. Differential abundance analysis followed by functional profiling, was used to identify and interpret protein changes. RESULTS: An increase in protein differential abundance in late-onset preeclampsia was observed with advancing gestation, reaching 806 proteins at T3 related to angiogenesis, cell adhesion, and extracellular matrix remodeling. FAAH2 (fatty acid amide hydrolase 2), SIGLEC6 (sialic acid-binding Ig-like lectin-6), IL17RC (interleukin-17 receptor C), HTRA1 (serine protease), sFlt-1, and 47 other proteins dysregulated at T3 were validated in a reanalysis of a ≈5000 protein Norwegian data set. Random forest models with 20 proteins showed high accuracy at T3 (area under the curve [AUC], 0.83 [0.77–0.89], sensitivity 59%) even in cases not yet diagnosed at sampling (n=31, AUC, 0.80 [0.71–0.90], sensitivity 58%), outperforming sFlt-1 and PlGF. Moderate accuracy was obtained at T1 (AUC, 0.63 [0.54–0.72], sensitivity 33%) and T2 (AUC, 0.59 [0.50–0.68], sensitivity 17%). Combining maternal characteristics and obstetric history with proteomics data increased accuracy at T1 (AUC, 0.68 [0.59–0.77], sensitivity 28%), T2 (AUC, 0.68 [0.60–0.77], sensitivity 31%), and T3 (AUC, 0.87 [0.81–0.92], sensitivity 69%). CONCLUSIONS: The findings confirm the involvement of abnormal trophoblast invasion, angiogenesis, and extracellular matrix remodeling in late-onset preeclampsia, while highlighting new protein alterations consistent across diverse cohorts.

• Westerberg, Ane Cecilie; Degnes, Maren-Helene Langeland; Andresen, Ina Jungersen; Sellevoll, Hilde Bastøe; Lekva, Tove & Ueland, Thor [Show all 11 contributors for this article] (2025). Placenta-Derived Proteins in Preeclampsia: A Human In Vivo Study. Hypertension. ISSN 0194-911X. 82(12), p. 2125–2139. doi: 10.1161/hypertensionaha.125.24886. Full text in Research Archive Show summary

  BACKGROUND: Placental dysfunction, a key feature of preeclampsia, has been linked to altered placental release of proteins into the maternal circulation. However, the identity of placenta-derived proteins in preeclampsia is unclear due to the inaccessibility of the placenta during pregnancy. This study aimed to identify placenta-derived proteins in preeclampsia, characterize their associated biological processes, and assess their biomarker potential. METHODS: We used the 4-vessel sampling method to collect blood from the ingoing and outgoing vessels of the placenta during cesarean section to identify proteins secreted from the placenta. Prospectively collected samples from a separate pregnancy cohort were also included. Proteins were quantified on the SomaLogic 5000-plex platform. RESULTS: We identified 620 placenta-derived proteins, including 229 proteins released in both healthy pregnancies and in preeclampsia, 345 proteins released in preeclampsia only, and 46 proteins released in healthy controls only. Biological process gene ontologies linked to oxidative stress and cellular turnover were enriched among the placenta-derived proteins in preeclampsia, but not in healthy pregnancies. In the prospective cohort, 21 of the 620 placenta-derived proteins had altered levels in preeclampsia at least 3 weeks before, and on average >7 weeks before delivery. Among these, prediction performance for preeclampsia was promising for 11 biomarker candidates in single protein models (area under the curve >0.7) and 17 significantly improved prediction when combined with clinical variables as compared with a clinical model alone. CONCLUSIONS: Using a unique in vivo sampling method, we identified placenta-derived proteins in preeclampsia, several of which showed promising biomarker potential.

• Andresen, Ina Jungersen; Westerberg, Ane Cecilie; Roland, Marie Cecilie; Zucknick, Manuela & Michelsen, Trond Melbye (2025). Maternal Plasma Proteins Associated with Birth Weight: A Longitudinal, Large Scale Proteomic Study. Journal of Proteome Research. ISSN 1535-3893. 24, p. 3247–3260. doi: 10.1021/acs.jproteome.4c00940. Full text in Research Archive Show summary

  Small infants for gestational age (SGA) and large infants for gestational age (LGA) have increased risk of complications during delivery and later in life. Prediction of the fetal weight is currently limited to biometric parameters obtained by ultrasound scans that can be imprecise. Biomarkers of fetal growth would be crucial for tailoring clinical management and optimizing outcomes for the mother and child. Seventy pregnant women participated in the current study, including 58, 7, and 5 giving birth to adequate for gestational age (AGA), SGA, and LGA infants, respectively. Maternal venous blood was drawn at gestational weeks 12–19, 21–27, and 28–34 and quantified for nearly 5000 proteins on the SomaLogic platform. We used machine learning algorithms with leave-one-out cross-validation to construct multiprotein models for prediction of birth weight groups. Random forest models using only 20 predefined proteins (selected by moderated t tests) were able to predict LGA with good discrimination (AUC > 0.8) at all three visits, while prediction of SGA was less successful. Protein differential abundance analysis revealed 148 proteins with higher abundance in LGA compared to AGA pregnancies, while only four proteins were differentially abundant between the SGA and AGA. The principal findings indicate that the maternal plasma proteome may hold potential biomarkers of LGA.

• Andresen, Ina Jungersen; Zucknick, Manuela; Degnes, Maren-Helene Langeland; Angst, Martin S.; Aghaeepour, Nima & Romero, Roberto [Show all 10 contributors for this article] (2024). Prediction of late-onset preeclampsia using plasma proteomics: a longitudinal multi-cohort study. Scientific Reports. 14(1). doi: 10.1038/s41598-024-81277-2. Full text in Research Archive Show summary

  Preeclampsia is a pregnancy disorder with substantial perinatal and maternal morbidity and mortality. Pregnant women at risk of preeclampsia would benefit from early detection for follow-up, timely interventions and delivery. Several attempts have been made to identify protein biomarkers of preeclampsia, but findings vary with demographics, clinical characteristics, and time of sampling. In the current study, we combined three independent longitudinal pregnancy cohorts (Detroit, Stanford and Oslo) resulting in 124 late-onset preeclampsia (LOPE) cases and 178 gestational age matched controls, and analyzed > 1000 proteins in maternal plasma sampled between 12 and 34 weeks of gestation. Differential abundance analysis of combined protein data revealed increased deviation in protein abundance trajectories throughout gestation in women destined to develop LOPE compared to controls. There were no differentially abundant proteins at time interval T1 (12–19 weeks), yet 31 differentially abundant proteins were found at time interval T2 (19–27 weeks), and 48 proteins at time interval T3 (27- 34 weeks). Multi-protein random forest models assessed via cross-validation predicted LOPE with an area under the ROC curve of 0.72 (0.65–0.78), 0.76 (0.71–0.81) and 0.80 (0.75–0.85) at time interval T1, T2 and T3, respectively. The results at T3 were confirmed using a leave-one-cohort-out analysis suggesting cross-cohort consistency, and at T1 and T2 when the largest two cohorts were used as training sets.

• Degnes, Maren-Helene Langeland; Westerberg, Ane Cecilie; Andresen, Ina Jungersen; Henriksen, Tore; Roland, Marie Cecilie & Zucknick, Manuela [Show all 7 contributors for this article] (2024). Protein biomarker signatures of preeclampsia - a longitudinal 5000-multiplex proteomics study. Scientific Reports. 14(1). doi: 10.1038/s41598-024-73796-9. Full text in Research Archive Show summary

  We aimed to explore novel biomarker candidates and biomarker signatures of late-onset preeclampsia (LOPE) by profiling samples collected in a longitudinal discovery cohort with a high-throughput proteomics platform. Using the Somalogic 5000-plex platform, we analyzed proteins in plasma samples collected at three visits (gestational weeks (GW) 12–19, 20–26 and 28–34 in 35 women with LOPE (birth ≥ 34 GW) and 70 healthy pregnant women). To identify biomarker signatures, we combined Elastic Net with Stability Selection for stable variable selection and validated their predictive performance in a validation cohort. The biomarker signature with the highest predictive performance (AUC 0.88 (95% CI 0.85–0.97)) was identified in the last trimester of pregnancy (GW 28–34) and included the Fatty acid amid hydrolase 2 (FAAH2), HtrA serine peptidase 1 (HTRA1) and Interleukin-17 receptor C (IL17RC) together with sFLT1 and maternal age, BMI and nulliparity. Our biomarker signature showed increased or similar predictive performance to the sFLT1/PGF-ratio within our data set, and we were able to validate the biomarker signature in a validation cohort (AUC ≥ 0.90). Further validation of these candidates should be performed using another protein quantification platform in an independent cohort where the negative and positive predictive values can be validly calculated.

• Westerberg, Ane Cecilie; Degnes, Maren-Helene Langeland; Andresen, Ina Jungersen; Roland, Marie Cecilie & Michelsen, Trond Melbye (2024). Angiogenic and vasoactive proteins in the maternal-fetal interface in healthy pregnancies and preeclampsia. American Journal of Obstetrics and Gynecology. ISSN 0002-9378. 231(5), p. 550.e1–550.e22. doi: 10.1016/j.ajog.2024.03.012. Full text in Research Archive Show summary

  Background Preeclampsia is characterized by maternal endothelial activation and placental dysfunction. Imbalance in maternal angiogenic and vasoactive factors has been linked to the pathophysiology. The contribution of the placenta as a source of these factors remains unclear. Furthermore, little is known about fetal angiogenic and vasoactive proteins and the relation between maternal and fetal levels. Objective We describe placental growth factor, soluble Fms-like tyrosine kinase 1, soluble endoglin, and endothelin 1–3 in 5 vessels in healthy pregnancies, early- and late-onset preeclampsia. Specifically, we aimed to (1) compare protein abundance in vessels at the maternal-fetal interface between early- and late-onset preeclampsia, and healthy pregnancies, (2) describe placental uptake and release of proteins, and (3) describe protein abundance in the maternal vs fetal circulations. Study Design Samples were collected from the maternal radial artery, uterine vein and antecubital vein, and fetal umbilical vein and artery in 75 healthy and 37 preeclamptic mother-fetus pairs (including 19 early-onset preeclampsia and 18 late-onset preeclampsia), during scheduled cesarean delivery. This method allows estimation of placental release and uptake of proteins by calculation of venoarterial differences on each side of the placenta. The microarray-based SomaScan assay quantified the proteins. Results The abundance of soluble Fms-like tyrosine kinase 1 and endothelin 1 was higher in the maternal vessels in preeclampsia than in healthy pregnancies, with the highest abundance in early-onset preeclampsia. Placental growth factor was lower in the maternal vessels in early-onset preeclampsia than in both healthy and late-onset preeclampsia. Maternal endothelin 2 was higher in preeclampsia, with late-onset preeclampsia having the highest abundance. Our model confirmed placental release of placental growth factor and soluble Fms-like tyrosine kinase 1 to the maternal circulation in all groups. The placenta released soluble Fms-like tyrosine kinase 1 into the fetal circulation in healthy and late-onset preeclampsia pregnancies. Fetal endothelin 1 and soluble Fms-like tyrosine kinase 1 were higher in early-onset preeclampsia, whereas soluble endoglin and endothelin 3 were lower in both preeclampsia groups than healthy controls. Across groups, abundances of placental growth factor, soluble Fms-like tyrosine kinase 1, and endothelin 3 were higher in the maternal artery than the fetal umbilical vein, whereas endothelin 2 was lower. Conclusion An increasing abundance of maternal soluble Fms-like tyrosine kinase 1 and endothelin 1 across the groups healthy, late-onset preeclampsia and early-onset combined with a positive correlation may suggest that these proteins are associated with the pathophysiology and severity of the disease. Elevated endothelin 1 in the fetal circulation in early-onset preeclampsia represents a novel finding. The long-term effects of altered protein abundance in preeclampsia on fetal development and health remain unknown. Further investigation of these proteins’ involvement in the pathophysiology and as treatment targets is warranted.

• Gulbrandsen, Øyvind Sætren; Andresen, Ina Jungersen; Krabberød, Anders Kristian; Bråte, Jon & Shalchian-Tabrizi, Kamran (2021). Phylogenomic analysis restructures the Ulvophyceae. Journal of Phycology. ISSN 0022-3646. 57(4), p. 1223–1233. doi: 10.1111/jpy.13168. Full text in Research Archive Show summary

  Here, we present new transcriptome sequencing data from seven species of Dasycladales (Ulvophyceae) and a phylogenomic analysis of the Chlorophyta with a particular focus on Ulvophyceae. We have focused on a broad selection of green algal groups and carefully selected genes suitable for reconstructing deep eukaryote evolutionary histories. Increasing the taxon sampling of Dasycladales restructures the Ulvophyceae by identifying Dasycladales as closely related to Scotinosphaerales and Oltmannsiellopsidales. Contrary to previous studies, we do not find support for a close relationship between Dasycladales and a group with Cladophorales and Trentepohliales. Instead, the latter group is sister to the remainder of the Ulvophyceae. Furthermore, our analyses show high and consistent statistical support for a sister relationship between Bryopsidales and Chlorophyceae in trees generated with both homogeneous and heterogeneous (heterotachy) evolutionary models. Our study provides a new framework for interpreting the evolutionary history of Ulvophyceae and the evolution of cellular morphologies.

• Andresen, Ina J.; Orr, Russell John Scott; Shalchian-Tabrizi, Kamran & Bråte, Jon (2021). Compartmentalization of mRNAs in the giant, unicellular green alga Acetabularia acetabulum. Algal Research. ISSN 2211-9264. 59. doi: 10.1016/j.algal.2021.102440. Full text in Research Archive Show summary

  Acetabularia acetabulum is a single-celled green alga which has historically been an important model system in cell biology. Here, we attempt to re-introduce A. acetabulum as a model system through the investigation of the subcellular localization of mRNAs. A. acetabulum is a macroscopic single-celled alga with a highly complex cellular morphology. The cell is gigantic, and the single nucleus, which is located at the basal end, is several centimeters away from the umbrella-shaped tip. To better understand the genetic basis of the morphology of this alga, we aimed to characterize the mRNA composition in four different subcellular regions of adult cells. Analyses of the quantitative gene expression data revealed a high degree of differentially distributed gene products. Gene transcripts involved in photosynthesis were mainly accumulated in the apical cap structure, while the basal end carrying the nucleus was enriched for nuclear processes such as DNA replication and transcription. Cytoskeletal components, intracellular transport and protein translation was present throughout this highly elongated cell. An important observation was that some gene transcripts were distributed throughout the cell while others, often functionally related transcripts, were localized in large pools at distinct subcellular regions. This suggests that post-transcriptional regulation and specific cellular localization of gene products may be important mechanisms behind morphogenesis in this gigantic cell.

• Andresen, Ina Jungersen; Orr, Russell John Scott; Krabberød, Anders Kristian; Shalchian-Tabrizi, Kamran & Bråte, Jon (2021). Genome sequencing and de novo assembly of the giant unicellular alga Acetabularia acetabulum using droplet MDA. Scientific Reports. 11. doi: 10.1038/s41598-021-92092-4. Full text in Research Archive

View all works in NVA

• Degnes, Maren-Helene Langeland; Westerberg, AC; Andresen, Ina Jungersen; Zucknick, Manuela; Powell, Theresa L & Jansson, Thomas [Show all 9 contributors for this article] (2022). Six placenta-derived proteins as markers of placental function. Full text in Research Archive
• Andresen, Ina Jungersen; Degnes, Maren-Helene Langeland; Zucknick, Manuela; Powell, Theresa L; Jansson, Thomas & Henriksen, Tore [Show all 8 contributors for this article] (2022). Protein biomarkers of late-onset preeclampsia. Full text in Research Archive
• Westerberg, AC; Degnes, Maren-Helene Langeland; Andresen, Ina Jungersen; Zucknick, Manuela; Powell, Theresa L & Jansson, Thomas [Show all 9 contributors for this article] (2022). Pleiotrophin and Fatty-acid Amide Hydrolase 2 – Placenta-derived Biomarkers of Preeclampsia? Full text in Research Archive
• Røsæg, Line Lieblein; Evenstad, Andreas; Andresen, Ina Jungersen; Bråte, Jon & Shalchian-Tabrizi, Kamran (2016). Postembryonic development of Mnemiopsis leidyi inferred from gene expression data. Full text in Research Archive
• Evenstad, Andreas; Røsæg, Line Lieblein; Andresen, Ina Jungersen; Shalchian-Tabrizi, Kamran & Bråte, Jon (2016). Evolution of non-coding RNAs in ctenophores. Full text in Research Archive

View all works in NVA