Targeted gene expression profiling for accurate endometrial receptivity testing

Abstract Expressional profiling of the endometrium enables the personalised timing of the window of implantation (WOI). This study presents and evaluates a novel analytical pipeline based on a TAC-seq (Targeted Allele Counting by sequencing) method for endometrial dating. The expressional profiles w...

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Main Authors: Alvin Meltsov, Merli Saare, Hindrek Teder, Priit Paluoja, Riikka K. Arffman, Terhi Piltonen, Piotr Laudanski, Mirosław Wielgoś, Luca Gianaroli, Mariann Koel, Maire Peters, Andres Salumets, Kaarel Krjutškov, Priit Palta
Format: Article
Language:English
Published: Nature Portfolio 2023-08-01
Series:Scientific Reports
Online Access:https://doi.org/10.1038/s41598-023-40991-z
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author Alvin Meltsov
Merli Saare
Hindrek Teder
Priit Paluoja
Riikka K. Arffman
Terhi Piltonen
Piotr Laudanski
Mirosław Wielgoś
Luca Gianaroli
Mariann Koel
Maire Peters
Andres Salumets
Kaarel Krjutškov
Priit Palta
author_facet Alvin Meltsov
Merli Saare
Hindrek Teder
Priit Paluoja
Riikka K. Arffman
Terhi Piltonen
Piotr Laudanski
Mirosław Wielgoś
Luca Gianaroli
Mariann Koel
Maire Peters
Andres Salumets
Kaarel Krjutškov
Priit Palta
author_sort Alvin Meltsov
collection DOAJ
description Abstract Expressional profiling of the endometrium enables the personalised timing of the window of implantation (WOI). This study presents and evaluates a novel analytical pipeline based on a TAC-seq (Targeted Allele Counting by sequencing) method for endometrial dating. The expressional profiles were clustered, and differential expression analysis was performed on the model development group, using 63 endometrial biopsies spanning over proliferative (PE, n = 18), early-secretory (ESE, n = 18), mid-secretory (MSE, n = 17) and late-secretory (LSE, n = 10) endometrial phases of the natural cycle. A quantitative predictor model was trained on the development group and validated on sequenced samples from healthy women, consisting of 52 paired samples taken from ESE and MSE phases and five LSE phase samples from 31 individuals. Finally, the developed test was applied to 44 MSE phase samples from a study group of patients diagnosed with recurrent implantation failure (RIF). In validation samples (n = 57), we detected displaced WOI in 1.8% of the samples from fertile women. In the RIF study group, we detected a significantly higher proportion of the samples with shifted WOI than in the validation set of samples from fertile women, 15.9% and 1.8% (p = 0.012), respectively. The developed model was evaluated with an average cross-validation accuracy of 98.8% and an accuracy of 98.2% in the validation group. The developed beREADY screening model enables sensitive and dynamic detection of selected transcriptome biomarkers, providing a quantitative and accurate prediction of endometrial receptivity status.
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spelling doaj.art-5fb92c738fde4f878dd96a1928826e5a2023-11-20T09:12:57ZengNature PortfolioScientific Reports2045-23222023-08-0113111210.1038/s41598-023-40991-zTargeted gene expression profiling for accurate endometrial receptivity testingAlvin Meltsov0Merli Saare1Hindrek Teder2Priit Paluoja3Riikka K. Arffman4Terhi Piltonen5Piotr Laudanski6Mirosław Wielgoś7Luca Gianaroli8Mariann Koel9Maire Peters10Andres Salumets11Kaarel Krjutškov12Priit Palta13Competence Centre On Health TechnologiesCompetence Centre On Health TechnologiesCompetence Centre On Health TechnologiesCompetence Centre On Health TechnologiesDepartment of Obstetrics and Gynecology, PEDEGO Research Unit, Medical Research Center, Oulu University Hospital, University of OuluDepartment of Obstetrics and Gynecology, PEDEGO Research Unit, Medical Research Center, Oulu University Hospital, University of OuluOviklinika Infertility CenterMedical Faculty, Lazarski UniversitySISMeR, Reproductive Medicine InstituteInstitute of Genomics, University of TartuCompetence Centre On Health TechnologiesCompetence Centre On Health TechnologiesCompetence Centre On Health TechnologiesCompetence Centre On Health TechnologiesAbstract Expressional profiling of the endometrium enables the personalised timing of the window of implantation (WOI). This study presents and evaluates a novel analytical pipeline based on a TAC-seq (Targeted Allele Counting by sequencing) method for endometrial dating. The expressional profiles were clustered, and differential expression analysis was performed on the model development group, using 63 endometrial biopsies spanning over proliferative (PE, n = 18), early-secretory (ESE, n = 18), mid-secretory (MSE, n = 17) and late-secretory (LSE, n = 10) endometrial phases of the natural cycle. A quantitative predictor model was trained on the development group and validated on sequenced samples from healthy women, consisting of 52 paired samples taken from ESE and MSE phases and five LSE phase samples from 31 individuals. Finally, the developed test was applied to 44 MSE phase samples from a study group of patients diagnosed with recurrent implantation failure (RIF). In validation samples (n = 57), we detected displaced WOI in 1.8% of the samples from fertile women. In the RIF study group, we detected a significantly higher proportion of the samples with shifted WOI than in the validation set of samples from fertile women, 15.9% and 1.8% (p = 0.012), respectively. The developed model was evaluated with an average cross-validation accuracy of 98.8% and an accuracy of 98.2% in the validation group. The developed beREADY screening model enables sensitive and dynamic detection of selected transcriptome biomarkers, providing a quantitative and accurate prediction of endometrial receptivity status.https://doi.org/10.1038/s41598-023-40991-z
spellingShingle Alvin Meltsov
Merli Saare
Hindrek Teder
Priit Paluoja
Riikka K. Arffman
Terhi Piltonen
Piotr Laudanski
Mirosław Wielgoś
Luca Gianaroli
Mariann Koel
Maire Peters
Andres Salumets
Kaarel Krjutškov
Priit Palta
Targeted gene expression profiling for accurate endometrial receptivity testing
Scientific Reports
title Targeted gene expression profiling for accurate endometrial receptivity testing
title_full Targeted gene expression profiling for accurate endometrial receptivity testing
title_fullStr Targeted gene expression profiling for accurate endometrial receptivity testing
title_full_unstemmed Targeted gene expression profiling for accurate endometrial receptivity testing
title_short Targeted gene expression profiling for accurate endometrial receptivity testing
title_sort targeted gene expression profiling for accurate endometrial receptivity testing
url https://doi.org/10.1038/s41598-023-40991-z
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