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Model averaging approach is an effective technique in alleviating the risk of misspecification and improving prediction accuracy for datasets with high dimension. When the datasets consist of sensi...

This paper proposes an algorithm for the classification of multi-dimensional datasets based on the conjugate Bayesian Multiple Kernel Grouping Learning (BMKGL). Using conjugate Bayesian framework i...

Additional file 1 Supplementary Materials include six sections: Section 1, Graph-based Change-point Detection; Section 2, Details of Algorithm 1; Section 3, More Simulations; Section 4, Analysis of the Effects of Gene Sets; Section 5, Challenge Results; and Section 6, Figures.

Context: Recently, two patients with primary ovarian insufficiency (POI) delivered healthy babies after in vitro activation (IVA) treatment followed by auto-transplantation of frozen-thawed ovarian tissues. Objective: This study sought to report the first case of live birth after IVA treatment following fresh ovarian tissue grafting in patients with POI, together with monitoring of follicle development and serum hormonal changes. Design: This was a prospective observational cohort study. Setting: We performed IVA treatment in 14 patients with POI with mean age of 29 years, mean duration since last menses of 3.8 years, and average basal FSH level of 94.5 mIU/mL. Interventions: Prior to IVA treatment, all patients received routine hormonal treatments with no follicle development. We removed one ovary from patients with POI and treated them with Akt stimulators. We improved upon early procedures by grafting back fresh tissues using a simplified protocol. Main Outcome Measures: In six of the 14 patients (43%), a total of 15 follicle development waves were detected, and four patients had successful oocyte retrieval to yield six oocytes. For two patients showing no spontaneous follicle growth, human menopausal gonadotropin treatment induced follicle growth at 6–8 months after grafting. After vitro fertilization of oocyte retrieved, four early embryos were derived. Following embryo transfer, one patient became pregnant and delivered a healthy baby boy, with three other embryos under cryopreservation. Conclusion: IVA technology can effectively activate residual follicles in some patients with POI and allow them to conceive their own genetic offspring. IVA may also be useful for treating patients with ovarian dysfunction including aging women and cancer survivors., We performed in vitro activation treatment following fresh ovarian tissue grafting in primary ovarian insufficiency patients, and achieved the first case of live birth with this method.

Background Deciphering the relationship between clinical responses and gene expression profiles may shed light on the mechanisms underlying diseases. Most existing literature has focused on exploring such relationship from cross-sectional gene expression data. It is likely that the dynamic nature of time-series gene expression data is more informative in predicting clinical response and revealing the physiological process of disease development. However, it remains challenging to extract useful dynamic information from time-series gene expression data. Results We propose a statistical framework built on considering co-expression network changes across time from time series gene expression data. It first detects change point for co-expression networks and then employs a Bayesian multiple kernel learning method to predict exposure response. There are two main novelties in our method: the use of change point detection to characterize the co-expression network dynamics, and the use of kernel function to measure the similarity between subjects. Our algorithm allows exposure response prediction using dynamic network information across a collection of informative gene sets. Through parameter estimations, our model has clear biological interpretations. The performance of our method on the simulated data under different scenarios demonstrates that the proposed algorithm has better explanatory power and classification accuracy than commonly used machine learning algorithms. The application of our method to time series gene expression profiles measured in peripheral blood from a group of subjects with respiratory viral exposure shows that our method can predict exposure response at early stage (within 24 h) and the informative gene sets are enriched for pathways related to respiratory and influenza virus infection. Conclusions The biological hypothesis in this paper is that the dynamic changes of the biological system are related to the clinical response. Our results suggest that when the relationship between the clinical response and a single gene or a gene set is not significant, we may benefit from studying the relationships among genes in gene sets that may lead to novel biological insights.

Previous studies have shown that long noncoding RNAs (lncRNAs) show a highly tissue- and disease-specific expression pattern and that they regulate the expression of neighboring genes. Because lncRNAs have been shown to be secreted into the general circulation, they may be used as diagnostic tools for some diseases. Primary ovarian insufficiency (POI) is a disease in which women have menstrual cessation before the age of 40, accompanied by elevated follicle stimulating hormone and decreased estrogen levels. In this study, ovarian cortical tissues from five women with normal menstrual cycles and from five POI patients were used for next-generation RNA sequencing. We found 20 differentially expressed lncRNAs with 12 upregulated and eight downregulated lncRNAs in cortical tissues of POI ovaries, compared with normal controls (fold change ≥ 2 and false discovery rate[FDR] ≤ 0.05). We also found 52 differentially expressed messenger RNA transcripts, with 33 upregulated and 19 downregulated ones (foldchange ≥ 2 and FDR ≤ 0.05). Functional annotation showed that these differentially expressed transcripts were associated with follicular development and granulosa cell function. Thirteen differentially expressed lncRNAs and their targeted neighboring transcripts were coregulated in ovarian cortical tissues, including lnc-ADAMTS1-1:1/ADAMTS1, lnc-PHLDA3-3:2/CSRP1, lnc-COL1A1-5:1/COL1A1, lnc-SAMD14-5:3/COL1A1, and lnc-GULP1-2:1/COL3A1. Furthermore, serum levels of these lncRNAs in POI patients were significantly different from those in normal patients ( p < 0.05), and expression differences were consistent with those in ovarian cortical tissues. This study showed that key lncRNAs were differentially expressed in both ovarian cortical tissues and serum samples between women with normal menstrual cycles and POI patients. Further studies on the regulation of ovarian lncRNAs during follicular development are critical in understanding the etiologies of POI. Analyses of lncRNA expression in serum samples might provide a basis for early diagnosis and treatment of POI.

Reciprocal translocations (RecT) and Robertsonian translocations (RobT) are among the most common chromosomal abnormalities that cause infertility and birth defects. Preimplantation genetic testing for aneuploidy using comprehensive chromosome screening for in vitro fertilization enables embryo selection with balanced chromosomal ploidy; however, it is normally unable to determine whether an embryo is a translocation carrier. Here we report a method named “Mapping Allele with Resolved Carrier Status” (MaReCs), which enables chromosomal ploidy screening and resolution of the translocation carrier status of the same embryo. We performed MaReCs on 108 embryos, of which 96 were from 13 RecT carriers and 12 were from three RobT carriers. Thirteen of the sixteen patients had at least one diploid embryo. We have confirmed the accuracy of our carrier status determination in amniotic fluid karyotyping of seven cases as well as in the live birth we have thus far. Therefore, MaReCs accurately enables the selection of translocation-free embryos from patients carrying chromosomal translocations. We expect MaReCs will help reduce the propagation of RecT/RobT in the human population.

Introduction Reciprocal translocations (RecT) and Robertsonian translocations (RobT) are among the most common chromosomal abnormalities that cause infertility and birth defects. Preimplantation genetic testing for aneuploidy using comprehensive chromosome screening for in vitro fertilization enables embryo selection with balanced chromosomal ploidy. However, it is normally unable to determine whether an embryo is a translocation carrier. We have reported a method named “Mapping Allele with Resolved Carrier Status” (MaReCs), which enables chromosomal ploidy screening and resolution of the translocation carrier status of the same embryo ( J. Xu et al. 2017 ). Here we introduce MaReCs and update the clinical study results. Material & Methods From September, 2017 to now, we have performed MaReCs on 69 patients, among them 55 were RecT carriers and 14 were RobT carriers. Result Totally 176 embryos from patients were identified ploidy-balanced, of which embryos from 41 patients were successfully identified as normal or balanced translocation. Other embryos’ translocation status could not be identified because of lacking reference embryos and these patients have accepted further identification in next cycles. And we have confirmed the accuracy of our carrier status determination in amniotic fluid karyotyping of seven cases as well as in the live birth we have thus far. Conclusions MaReCs accurately enables the selection of translocation-free embryos from patients carrying chromosomal translocations. It can work as an effective technology to help reduce the propagation of RecT/RobT in the human population.

Phytoavailability and uptake mechanism of Cd in edible plant tissues grown on metal polluted agricultural soils has become a growing concern worldwide. Uptake, transport, accumulation and localization of cadmium in potato organs under different soil Cd levels were investigated using inductively-coupled plasma mass spectrometry and energy dispersive X-ray microanalysis. Results indicated that Cd contents in potato organs increased with increasing soil Cd concentrations, and the order of Cd contents in different organs was leaves > stems/roots > tubers. Root-to-stem Cd translocation coefficients ranged from 0.89 to 1.81. Cd localization in potato tissues suggested that leaves and stems should be the main compartment of Cd storage and uptake. Although low concentrations of Cd migrated from the root to tuber, Cd accumulation in the tuber exceeded the standard for food security. Therefore, the planting of potato plants in farmland containing Cd should be closely evaluated due to its potential to present health risks.

We explored the application of single nucleotide polymorphism microarray (SNP array) in molecular karyotype analysis for early spontaneous abortion detection in assisted reproductive technology (ART). SNP array was performed in 81 cases. Of the 81 cases, 16 experienced natural conception (NC) and 65 were pregnant by ART. Of the 65 cases, 4 underwent artificial insemination (AI), 32 fresh in vitro fertilization-embryo transfer (IVF-ET), 9 fresh intracytoplasmic sperm injection (ICSI), and 20 thawed embryo transfer. In the 81 cases examined 69.1% displayed an abnormal molecular karyotype. In the subjects greater than 35 years of age, the abnormal molecular karyotype rate was 87.5% higher compared to 61.4% in younger individuals (P < 0.05). There was no significant difference in the abnormal molecular karyotype rate or type between ART (64.6%) and NC (87.5%). Compared with traditional cytogenetic diagnosis, the SNP array can identify a greater number of abnormal karyotypes.