Globally learning gene regulatory networks based on hidden atomic regulators from transcriptomic big data
BMC GENOMICS
Authors: Shi, Ming; Tan, Sheng; Xie, Xin-Ping; Li, Ao; Yang, Wulin; Zhu, Tao; Wang, Hong-Qiang
Abstract
Background Genes are regulated by various types of regulators and most of them are still unknown or unobserved. Current gene regulatory networks (GRNs) reverse engineering methods often neglect the unknown regulators and infer regulatory relationships in a local and sub-optimal manner. Results This paper proposes a global GRNs inference framework based on dictionary learning, named dlGRN. The method intends to learn atomic regulators (ARs) from gene expression data using a modified dictionary learning (DL) algorithm, which reflects the whole gene regulatory system, and predicts the regulation between a known regulator and a target gene in a global regression way. The modified DL algorithm fits the scale-free property of biological network, rendering dlGRN intrinsically discern direct and indirect regulations. Conclusions Extensive experimental results on simulation and real-world data demonstrate the effectiveness and efficiency of dlGRN in reverse engineering GRNs. A novel predicted transcription regulation between a TF TFAP2C and an oncogene EGFR was experimentally verified in lung cancer cells. Furthermore, the real application reveals the prevalence of DNA methylation regulation in gene regulatory system. dlGRN can be a standalone tool for GRN inference for its globalization and robustness.
Comparison of ambulatory central hemodynamics and arterial stiffness in patients with diabetic and non-diabetic CKD
JOURNAL OF CLINICAL HYPERTENSION
Authors: Loutradis, Charalampos; Schoina, Maria; Dimitroulas, Theodoros; Doumas, Michael; Garyfallos, Alexandros; Karagiannis, Asterios; Papagianni, Aikaterini; Sarafidis, Pantelis
Abstract
Increased arterial stiffness is independently associated with renal function decline in patients with diabetes mellitus (DM). Whether DM has additional deleterious effects on central hemodynamics and arterial stiffness in chronic kidney disease (CKD) patients is yet unknown. This study aimed to compare ambulatory central BP, arterial stiffness parameters, and trajectories between patients with diabetic and non-diabetic CKD. This study examined 48 diabetic and 48 non-diabetic adult patients (>18 years) with CKD (eGFR: <90 and >= 15 ml/min/1.73 m(2)), matched in a 1:1 ratio for age, sex, and eGFR within CKD stages (2, 3a, 3b and 4). All patients underwent 24-h ABPM with the Mobil-O-Graph device. Parameters of central hemodynamics [central systolic (cSBP) and diastolic blood pressure (cDBP), pulse pressure (PP)], wave reflection [augmentation index (AIx), and pressure (AP)] and pulse wave velocity (PWV) were estimated from the 24-h recordings. Diabetic CKD patients had higher 24-h cSBP (118.57 +/- 10.05 vs. 111.59 +/- 9.46, P = .001) and 24-h cPP (41.48 +/- 6.80 vs. 35.25 +/- 6.98, P < .001) but similar 24-h cDBP (77.09 +/- 8.14 vs. 76.34 +/- 6.75 mmHg, P = .625) levels compared to patients with non-diabetic CKD. During day- and nighttime periods, cSBP and cPP levels were higher in diabetics compared to non-diabetics. 24-h PWV (10.10 +/- 1.62 vs. 9.61 +/- 1.80 m/s, P = .165) was numerically higher in patients with DM, but no between-group differences were noted in augmentation pressure and index. In multivariate analysis, DM, female gender, and peripheral SBP were independently associated with higher cPP levels. Patients with diabetic CKD have higher ambulatory cSBP and increased arterial stiffness, as indicated by higher ambulatory cPP. These finding suggest that DM is a factor independently contributing to the adverse macrocirculatory profile of CKD patients.