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Abstract Background Many human disease phenotypes manifest differently by sex, making the development of methods for incorporating X and Y-chromosome data into analyses vital. Unfortunately, X and Y chromosome data are frequently excluded from large-scale analyses of the human genome and epigenome due to analytical complexity associated with sex chromosome dosage differences between XX and XY individuals, and the impact of X-chromosome inactivation (XCI) on the epigenome. As such, little attention has been given to considering the methods by which sex chromosome data may be included in analyses of DNA methylation (DNAme) array data. Results With Illumina Infinium HumanMethylation450 DNAme array data from 634 placental samples, we investigated the effects of probe filtering, normalization, and batch correction on DNAme data from the X and Y chromosomes. Processing steps were evaluated in both mixed-sex and sex-stratified subsets of the analysis cohort to identify whether including both sexes impacted processing results. We found that identification of probes that have a high detection p-value, or that are non-variable, should be performed in sex-stratified data subsets to avoid over- and under-estimation of the quantity of probes eligible for removal, respectively. All normalization techniques investigated returned X and Y DNAme data that were highly correlated with the raw data from the same samples. We found no difference in batch correction results after application to mixed-sex or sex-stratified cohorts. Additionally, we identify two analytical methods suitable for XY chromosome data, the choice between which should be guided by the research question of interest, and we performed a proof-of-concept analysis studying differential DNAme on the X and Y chromosome in the context of placental acute chorioamnionitis. Finally, we provide an annotation of probe types that may be desirable to filter in X and Y chromosome analyses, including probes in repetitive elements, the X-transposed region, and cancer-testis gene promoters. Conclusion While there may be no single “best” approach for analyzing DNAme array data from the X and Y chromosome, analysts must consider key factors during processing and analysis of sex chromosome data to accommodate the underlying biology of these chromosomes, and the technical limitations of DNA methylation arrays.

Abstract Background Human placental DNA methylation (DNAme) data is a valuable resource for studying sex differences during gestation, as DNAme profiles after delivery reflect the cumulative effects of gene expression patterns and exposures across gestation. Here, we present an analysis of sex differences in autosomal DNAme in the uncomplicated term placenta (n = 343) using the Illumina 450K array. Results At a false discovery rate < 0.05 and a mean sex difference in DNAme beta value of > 0.10, we identified 162 autosomal CpG sites that were differentially methylated by sex and replicated in an independent cohort of samples (n = 293). Several of these differentially methylated CpG sites were part of larger correlated regions of sex differential DNAme. Although global DNAme levels did not differ by sex, the majority of significantly differentially methylated CpGs were more highly methylated in male placentae, the opposite of what is seen in differential methylation analyses of somatic tissues. Patterns of autosomal DNAme at these 162 CpGs were significantly associated with maternal age (in males) and newborn birthweight standard deviation (in females). Conclusions Our results provide a comprehensive analysis of sex differences in autosomal DNAme in the term human placenta. We report a list of high-confidence autosomal sex-associated differentially methylated CpGs and identify several key features of these loci that suggest their relevance to sex differences observed in normative and complicated pregnancies.

This paper presents the first results from draw-a-scientist tests (DASTs) over five years that were used to measure the effect of 8–10 week long astronomy clubs and week long summer camps on 3 rd–5 th grade elementary school students’ perceptions of scientists. We facilitated these DASTs prior to these clubs or camps, which provide a baseline for a student’s initial conception of scientists, and once at the end, to determine whether their conception changed, possibly as a result of their involvement. In total we analyze 89 pairs of DASTs using a numerical grading scheme designed to quantify the presence of various features in the drawn scientist and their activities. We find that there is a gender imbalance in both the pre- and postclub drawings, with only 32% and 35%, respectively, of students drawing female scientists. We also find that a third to a half of the scientists have a stereotypical appearance and/or are performing stereotypical activities. Although we find insignificant changes (