In search of functional association from time-series microarray data based on the change trend and level of gene expression

BACKGROUND: The increasing availability of time-series expression data opens up new possibilities to study functional linkages of genes. Present methods used to infer functional linkages between genes from expression data are mainly based on a point-to-point comparison. Change trends between consecutive time points in time-series data have been so far not well explored. RESULTS: In this work we present a new method based on extracting main features of the change trend and level of gene expression between consecutive time points. The method, termed as trend correlation (TC), includes two major steps: 1, calculating a maximal local alignment of change trend score by dynamic programming and a change trend correlation coefficient between the maximal matched change levels of each gene pair; 2, inferring relationships of gene pairs based on two statistical extraction procedures. The new method considers time shifts and inverted relationships in a similar way as the local clustering (LC) method but the latter is merely based on a point-to-point comparison. The TC method is demonstrated with data from yeast cell cycle and compared with the LC method and the widely used Pearson correlation coefficient (PCC) based clustering method. The biological significance of the gene pairs is examined with several large-scale yeast databases. Although the TC method predicts an overall lower number of gene pairs than the other two methods at a same p-value threshold, the additional number of gene pairs inferred by the TC method is considerable: e.g. 20.5% compared with the LC method and 49.6% with the PCC method for a p-value threshold of 2.7E-3. Moreover, the percentage of the inferred gene pairs consistent with databases by our method is generally higher than the LC method and similar to the PCC method. A significant number of the gene pairs only inferred by the TC method are process-identity or function-similarity pairs or have well-documented biological interactions, including 443 known protein interactions and some known cell cycle related regulatory interactions. It should be emphasized that the overlapping of gene pairs detected by the three methods is normally not very high, indicating a necessity of combining the different methods in search of functional association of genes from time-series data. For a p-value threshold of 1E-5 the percentage of process-identity and function-similarity gene pairs among the shared part of the three methods reaches 60.2% and 55.6% respectively, building a good basis for further experimental and functional study. Furthermore, the combined use of methods is important to infer more complete regulatory circuits and network as exemplified in this study. CONCLUSION: The TC method can significantly augment the current major methods to infer functional linkages and biological network and is well suitable for exploring temporal relationships of gene expression in time-series data

Dynamic cumulative activity of transcription factors as a mechanism of quantitative gene regulation

By combining information on the yeast transcription network and high-resolution time-series data with a series of factors, support is provided for the concept that dynamic cumulative regulation is a major principle of quantitative transcriptional control

Endothelial Differentiation Gene-1, a New Downstream Gene Is Involved in RTEF-1 Induced Angiogenesis in Endothelial Cells

Related Transcriptional Enhancer Factor-1 (RTEF-1) has been suggested to induce angiogenesis through regulating target genes. Whether RTEF-1 has a direct role in angiogenesis and what specific genes are involved in RTEF-1 driven angiogenisis have not been elucidated. We found that over-expressing RTEF-1 in Human dermal microvascular endothelial cells-1 (HMEC-1) significantly increased endothelial cell aggregation, growth and migration while the processes were inhibited by siRNA of RTEF-1. In addition, we observed that Endothelial differentiation gene-1 (Edg-1) expression was up-regulated by RTEF-1 at the transcriptional level. RTEF-1 could bind to Edg-1 promoter and subsequently induce its activity. Edg-1 siRNA significantly blocked RTEF-1-driven increases in endothelial cell aggregation in a Matrigel assay and retarded RTEF-1-induced endothelial cell growth and migration. Pertussis Toxin (PTX), a Gi/Go protein sensitive inhibitor, was found to inhibit RTEF-1 driven endothelial cell aggregation and migration. Our data demonstrates that Edg-1 is a potential target gene of RTEF-1 and is involved in RTEF-1-induced angiogenesis in endothelial cells. Gi/Go protein coupled receptor pathway plays a role in RTEF-1 driven angiogenesis in endothelial cells

Friedel Oscillation-Induced Energy Gap Manifested as Transport Asymmetry at Monolayer-Bilayer Graphene Boundaries

We show that Friedel charge oscillation near an interface opens a gap at the Fermi energy for electrons with wave vectors perpendicular to the interface. If the Friedel gaps on two sides of the interface are different, a nonequlibrium effect - shifting of these gaps under bias - leads to asymmetric transport upon reversing the bias polarity. The predicted transport asymmetry is revealed by scanning tunneling potentiometry at monolayer-bilayer interfaces in epitaxial graphene on SiC (0001). This intriguing interfacial transport behavior opens a new avenue towards novel quantum functions such as quantum switching.Comment: accepted for publication in PR

1-(4-Amino-3,5-dichloro­phen­yl)ethanol

The asymmetric unit of the title compound, C8H9Cl2NO, contains two crystallographically independent mol­ecules which are connected via an N—H⋯O hydrogen bond . There is aromatic π–π stacking in the crystal, with a centroid–centroid distance between benzene rings of 3.48 (2)Å. The crystal packing is stabilized by intermolecular hydrogen bonds

A new polymorph of magnesium oxalate dihydrate

In the asymmetric unit of the title compound, catena-poly[[diaqua­magnesium(II)]-μ-oxalato], [Mg(C2O4)(H2O)2]n, there is one Mg atom in an octa­hedral coordination with site symmetry 222, a unique C atom of the oxalate anion lying on a twofold axis, an O atom of the anion in a general position and a water O atom at a site with imposed twofold rotation symmetry. The Mg2+ ions are ligated by water mol­ecules and bridged by the anions to form chains that are held together by O—H⋯O hydrogen bonds. The structure of the title compound has already been reported in a different space group [Lagier, Pezerat & Dubernat (1969 ▶). Rev. Chim. Miner. 6, 1081–1093; Levy, Perrotey & Visser (1971 ▶). Bull. Soc. Chim. Fr. pp. 757–761]

Effect of Neoadjuvant Chemoradiotherapy with Capecitabine versus Fluorouracil for Locally Advanced Rectal Cancer: A Meta-Analysis

A meta-analysis was carried out to compare the efficacy and safety of capecitabine plus radiation with 5-fluorouracil (5-FU) plus radiotherapy (RT) as neoadjuvant treatment in locally advanced rectal cancer (LARC). We searched the Cochrane database, Ovid, Medline, Embase, ISI databases, and Chinese Biomedical Literature Database between January 1998 and October 2014. Trials of capecitabine compared with 5-FU plus RT as neoadjuvant treatment for LARC were considered for inclusion. RevMan software was used to analyze these data. Nine trials were included in this meta-analysis, which covered a total of 3141 patients. The meta-analysis showed that capecitabine group had statistically significant better pCR rates (OR, 1.34; 95% CI, 1.10–1.64; P=0.003), T downstaging rates (OR, 1.58; 95% CI, 1.22–2.06; P=0.0007), N downstaging rates (OR, 2.06; 95% CI, 1.34–3.16; P=0.001), less distant metastasis (OR, 0.63; 95% CI, 0.44–0.88; P=0.007), and lowered leucocytes (OR, 0.25; 95% CI, 0.11–0.54; P=0.0005), but with higher incidence of hand-foot syndrome (HFS) (OR, 4.43; 95% CI, 1.59–12.33; P=0.004). Capecitabine was more efficient than 5-FU in terms of tumor response in neoadjuvant treatment for patients with LARC and favourably low toxicity with the exception of HFS