CoRE-ATAC: A deep learning model for the functional classification of regulatory elements from single cell and bulk ATAC-seq data.

Cis-Regulatory elements (cis-REs) include promoters, enhancers, and insulators that regulate gene expression programs via binding of transcription factors. ATAC-seq technology effectively identifies active cis-REs in a given cell type (including from single cells) by mapping accessible chromatin at base-pair resolution. However, these maps are not immediately useful for inferring specific functions of cis-REs. For this purpose, we developed a deep learning framework (CoRE-ATAC) with novel data encoders that integrate DNA sequence (reference or personal genotypes) with ATAC-seq cut sites and read pileups. CoRE-ATAC was trained on 4 cell types (n = 6 samples/replicates) and accurately predicted known cis-RE functions from 7 cell types (n = 40 samples) that were not used in model training (mean average precision = 0.80, mean F1 score = 0.70). CoRE-ATAC enhancer predictions from 19 human islet samples coincided with genetically modulated gain/loss of enhancer activity, which was confirmed by massively parallel reporter assays (MPRAs). Finally, CoRE-ATAC effectively inferred cis-RE function from aggregate single nucleus ATAC-seq (snATAC) data from human blood-derived immune cells that overlapped with known functional annotations in sorted immune cells, which established the efficacy of these models to study cis-RE functions of rare cells without the need for cell sorting. ATAC-seq maps from primary human cells reveal individual- and cell-specific variation in cis-RE activity. CoRE-ATAC increases the functional resolution of these maps, a critical step for studying regulatory disruptions behind diseases

Sexual-dimorphism in human immune system aging.

Differences in immune function and responses contribute to health- and life-span disparities between sexes. However, the role of sex in immune system aging is not well understood. Here, we characterize peripheral blood mononuclear cells from 172 healthy adults 22-93 years of age using ATAC-seq, RNA-seq, and flow cytometry. These data reveal a shared epigenomic signature of aging including declining naïve T cell and increasing monocyte and cytotoxic cell functions. These changes are greater in magnitude in men and accompanied by a male-specific decline in B-cell specific loci. Age-related epigenomic changes first spike around late-thirties with similar timing and magnitude between sexes, whereas the second spike is earlier and stronger in men. Unexpectedly, genomic differences between sexes increase after age 65, with men having higher innate and pro-inflammatory activity and lower adaptive activity. Impact of age and sex on immune phenotypes can be visualized at https://immune-aging.jax.org to provide insights into future studies

Effect Of G2706A and G1051A polymorphisms of the ABCA1 gene on the lipid, oxidative stress and homocystein levels in Turkish patients with polycystıc ovary syndrome

<p>Abstract</p> <p>Background</p> <p>Obesity, insulin resistance and hyperandrogenism, crucial parameters of Polycystic ovary syndrome (PCOS) play significant pathophysiological roles in lipidemic aberrations associated within the syndrome. Parts of the metabolic syndrome (low HDL and insulin resistance) appeared to facilitate the association between PCOS and coronary artery disease, independently of obesity. ABCA1 gene polymorphism may be altered this components in PCOS patients.</p> <p>In this study, we studied 98 PCOS patients and 93 healthy controls. All subjects underwent venous blood drawing for complete hormonal assays, lipid profile, glucose, insulin, malondialdehyde, nitric oxide, disulfide levels and ABCA genetic study.</p> <p>Results</p> <p>In PCOS group fasting glucose, DHEAS, 17-OHP, free testosterone, total-cholesterol, triglyceride, LDL-cholesterol and fibrinogen were significantly different compare to controls. The genotype ABCA G2706A distribution differed between the control group (GG 60.7%, GA 32.1%, AA 7.1%) and the PCOS patients (GG 8.7%, GA 8.7%, AA 76.8%). The frequency of the A allele (ABCAG2706A) was higher in PCOS patients than control group with 13,0% and 23,2%, respectively. In this study, the homocystein and insulin levels were significantly higher in PCOS patients with ABCA G1051A mutant genotype than those with heterozygote and wild genotypes.</p> <p>Conclusions</p> <p>We found higher percentage of AA genotype and A allele of ABCA G2706A in PCOS patients compare to controls. The fasting insulin and homocystein levels were significantly higher in PCOS patients with ABCA G1051A mutant genotype than those with heterozygote and wild genotypes.</p

AMULET: a novel read count-based method for effective multiplet detection from single nucleus ATAC-seq data.

Detecting multiplets in single nucleus (sn)ATAC-seq data is challenging due to data sparsity and limited dynamic range. AMULET (ATAC-seq MULtiplet Estimation Tool) enumerates regions with greater than two uniquely aligned reads across the genome to effectively detect multiplets. We evaluate the method by generating snATAC-seq data in the human blood and pancreatic islet samples. AMULET has high precision, estimated via donor-based multiplexing, and high recall, estimated via simulated multiplets, compared to alternatives and identifies multiplets most effectively when a certain read depth of 25K median valid reads per nucleus is achieved

Reference values for echocardiographic measurements of healthy newborns

Objective: To assess the reference values of M-mode echocardiographic measurements in healthy newborns according to body weight. Methods: From January, 2008 to June, 2008, a total of 250 - 130 female and 120 male - term healthy newborns were included in the study. M-mode echocardiographic measurements were recorded by a paediatric cardiologist in accordance with the American Society of Echocardiography recommendations. Right ventricular anterior wall end-diastolic thickness, right ventricular end-diastolic diameter, interventricular septum end-diastolic thickness, left ventricular end-diastolic diameter, left ventricular posterior wall end-diastolic thickness, interventricular septum end-systolic thickness, left ventricular end-systolic diameter, left ventricular posterior wall end-systolic thickness, aortic root dimension, left atrium dimension, left ventricular ejection, and shortening fraction were measured. Results: The values of echocardiographic measurements revealed a good correlation with body weight. When body weight increased, the measured values also increased in parallel. The measured values were not influenced by gender. Ejection and shortening fraction parameters did not change with body weight and gender. Conclusion: In this study, normative values related to body weight for cardiac chambers and wall thickness were determined in healthy newborns. These reference values can be used to evaluate whether newborns have normal or abnormal echocardiographic measurement

Prenatal Risk Factors for Congenital Anomalies of the Kidney and Urinary Tract

OBJECTIVE: Congenital anomalies of the kidney and urinary tract (CAKUT) are the leading cause of chronic renal disease in childhood. Abnormal intrauterine conditions as well as genetic disorders play role in CAKUT development. We evaluated antenatal factors in CAKUT

Dispersion of the P wave as a test for cardiac autonomic function in diabetic children

Objective: We aimed, in this study, to compare dispersion of the p wave in patients with type I diabetes to nondiabetic control subjects, and to investigate the relationship between the dispersion of the p wave and cardiac autonomic dysfunction in diabetic children. Methods: We enrolled 49 patients with type I diabetes, and 32 age- and sex-matched healthy subjects, measuring the Valsalva ratio, resting heart rate, and orthostatic hypotension in all. The duration of the p wave was measured manually on a high-resolution computer screen. Dispersion, defined as the difference between maximum and minimum durations of the p waves, was also measured in the 12-lead electrocardiogram before and after the Valsalva maneuver. Results: The mean age of the patients and their controls were 14.2 +/- 4.8 years, and 12.7 +/- 4.5 years, respectively. The mean duration of diabetes had been 6.2 +/- 4.6 years. Maximal and minimal values for the duration of the p wave were significantly decreased in the diabetic children, with the dispersion itself significantly increased. Values for the dispersion in the diabetic subjects were similar before and after the Valsalva maneuver, whereas dispersion was found significantly increased after this maneuver in the controls. The differences in the Valsalva ratio, resting heart rate, and orthostatic hypotension between the groups, on the other hand, were not found to be statistically significant. Conclusion: The noted increase in the dispersion of the p wave in diabetic children reveals the onset of cardiac electrophysiological heterogeneity before it is possible to detect parasympathetic and sympathetic dysfunction with other tests