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OALib Journal期刊

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Reconstructing Generalized Logical Networks of Transcriptional Regulation in Mouse Brain from Temporal Gene Expression Data
Song Mingzhou(Joe),Lewis Chris K,Lance Eric R,Chesler Elissa J
EURASIP Journal on Bioinformatics and Systems Biology , 2009,
Abstract: Gene expression time course data can be used not only to detect differentially expressed genes but also to find temporal associations among genes. The problem of reconstructing generalized logical networks to account for temporal dependencies among genes and environmental stimuli from transcriptomic data is addressed. A network reconstruction algorithm was developed that uses statistical significance as a criterion for network selection to avoid false-positive interactions arising from pure chance. The multinomial hypothesis testing-based network reconstruction allows for explicit specification of the false-positive rate, unique from all extant network inference algorithms. The method is superior to dynamic Bayesian network modeling in a simulation study. Temporal gene expression data from the brains of alcohol-treated mice in an analysis of the molecular response to alcohol are used for modeling. Genes from major neuronal pathways are identified as putative components of the alcohol response mechanism. Nine of these genes have associations with alcohol reported in literature. Several other potentially relevant genes, compatible with independent results from literature mining, may play a role in the response to alcohol. Additional, previously unknown gene interactions were discovered that, subject to biological verification, may offer new clues in the search for the elusive molecular mechanisms of alcoholism.
Reconstructing Generalized Logical Networks of Transcriptional Regulation in Mouse Brain from Temporal Gene Expression Data
Mingzhou(Joe) Song, Chris K Lewis, Eric R Lance, Elissa J Chesler, Roumyana Kirova Yordanova, Michael A Langston, Kerrie H Lodowski, Susan E Bergeson
EURASIP Journal on Bioinformatics and Systems Biology , 2009, DOI: 10.1155/2009/545176
Abstract: The regulation of transcription occurring in an intriguingly complex biological system involves multiple interacting regulatory processes in gene regulatory networks (GRNs). Modeling transcriptional regulation requires algorithms that retain information about regulatory interactions. The generalized logical network (GLN) is a generative model that can be reconstructed from temporal trajectories, for example, from data collected in time-series studies of gene expression. Because these data capture information on temporal antecedence, the approach can be used to develop stronger hypotheses about casual relations among transcriptional events than one would be able to derive from mere correlation analyses. We designed a GLN reconstruction algorithm that differs from previous approaches because it makes use of hypothesis testing on the multinomial distribution to establish directed connections among genes. Our statistical approach allows explicit control of false positives by specifying a desirable alpha level, while other criteria used in network reconstruction, such as the Bayesian information criterion (BIC) used in dynamic Bayesian networks (DBNs) reconstruction and the coefficient of determination (COD) used in Boolean networks (BNs) reconstruction, do not explicitly enforce false-positive rate control.GLNs also allow more aspects of systems to be studied than other network models by enabling (1) adaptive description for interactions among variables, (2) nonlinear interaction patterns, and (3) finite steady states, attractor basins, and state transition diagrams. The software CellNetAnalyzer [1] allows a user to draft a GLN from existing knowledge. Our method allows such networks to be reconstructed and derived solely from data-driven approaches. GLNs have the further advantage that they do not require parametric assumptions, unlike stochastic logical networks [2] which discretize differential equations based on strong assumptions. Additionally, our implementation o
Deciphering Interactions in Causal Networks without Parametric Assumptions
Yang Zhang,Mingzhou Song
Quantitative Biology , 2013,
Abstract: With the assumption that the effect is a mathematical function of the cause in a causal relationship, FunChisq, a chi-square test defined on a non-parametric representation of interactions, infers network topology considering both interaction directionality and nonlinearity. Here we show that both experimental and in silico biological network data suggest the importance of directionality as evidence for causality. Counter-intuitively, patterns in those interactions effectively revealed by FunChisq enlist an experimental design principle essential to network inference -- perturbations to a biological system shall make it transits between linear and nonlinear working zones, instead of operating only in a linear working zone.
Optimal In Silico Target Gene Deletion through Nonlinear Programming for Genetic Engineering
Chung-Chien Hong,Mingzhou Song
PLOS ONE , 2012, DOI: 10.1371/journal.pone.0009331
Abstract: Optimal selection of multiple regulatory genes, known as targets, for deletion to enhance or suppress the activities of downstream genes or metabolites is an important problem in genetic engineering. Such problems become more feasible to address in silico due to the availability of more realistic dynamical system models of gene regulatory and metabolic networks. The goal of the computational problem is to search for a subset of genes to knock out so that the activity of a downstream gene or a metabolite is optimized.
Roland Barthes' "Text" and aleatoric music: Is "The birth of the reader" the birth of the listener?
Jeongwon Joe,Song Hoo S.
Muzikologija , 2002, DOI: 10.2298/muz0202263j
Abstract: The history of Western classical music and the development of its notational system show that composers have tried to control more and more aspects of their compositions as precisely as possible. Total serialism represents the culmination of compositional control. Given this progressively increasing compositional control, the emergence of chance music, or aleatoric music, in the mid-twentieth century is a significantly interesting phenomenon. In aleatoric music, the composer deliberately incorporates elements of chance in the process of composition and/or in performance. Consequently, aleatoric works challenge the traditional notion of an art work as a closed entity fixed by its author. The philosophical root of aleatoric music can be traced to post structuralism, specifically its critique of the Enlightenment notion of the author as the creator of the meaning of his or her work. Roland Barthes' declaration of "the death of the author" epitomizes the Poststructuralists' position. Distinguishing "Text" from "Work," Barthes maintains that in a "Text," meanings are to be engendered not by the author but by the reader. Barthes conceives aleatoric music as an example of the "Text," which demands "the birth of the reader." This essay critically re-examines Barthes' notion of aleatoric music, focusing on the complicated status of the reader in music. The readers of a musical Text can be both performers and listeners. When Barthes' declaration of the birth of the reader is applied to the listener, it becomes problematic, since the listener, unlike the literary reader, does not have direct access to the "Text" but needs to be mediated by the performer. As Carl Dahlhaus has remarked, listeners cannot be exposed to other possible renditions that the performer could have chosen but did not choose, and in this respect, the supposed openness of an aleatoric piece is closed and fixed at the time of performance. In aleatoric music, it is not listeners but only performers who are promoted to the rank of co-author of the works. Finally, this essay explores the reason why Barthes turned to music for the purpose of illustrating his theory of text. What rhetorical role does music play in his articulation of "Work" and "Text"? Precisely because of music's "difference" as a performance art, music history provides the examples of the lowest and the highest moments in Barthes' theory of text, that is, those of Work and Text. If, for Barthes, the institutionalization of the professional performer in music history demonstrates the advent of Work better than literary examples, the
Nonmonotonic Pathway Gene Expression Analysis Reveals Oncogenic Role of p27/Kip1 at Intermediate Dose
Christopher J Kemp,Hien H Nguyen,Mingzhou Song,Susan C Tilton
- , 2017, DOI: 10.1177/1176935117740132
Abstract: The mechanistic basis by which the level of p27Kip1 expression influences tumor aggressiveness and patient mortality remains unclear. To elucidate the competing tumor-suppressing and oncogenic effects of p27Kip1 on gene expression in tumors, we analyzed the transcriptomes of squamous cell papilloma derived from Cdkn1b nullizygous, heterozygous, and wild-type mice. We developed a novel functional pathway analysis method capable of testing directional and nonmonotonic dose response. This analysis can reveal potential causal relationships that might have been missed by other nondirectional pathway analysis methods. Applying this method to capture dose-response curves in papilloma gene expression data, we show that several known cancer pathways are dominated by low-high-low gene expression responses to increasing p27 gene doses. The oncogene cyclin D1, whose expression is elevated at an intermediate p27 dose, is the most responsive gene shared by these cancer pathways. Therefore, intermediate levels of p27 may promote cellular processes favoring tumorigenesis—strikingly consistent with the dominance of heterozygous mutations in CDKN1B seen in human cancers. Our findings shed new light on regulatory mechanisms for both pro- and anti-tumorigenic roles of p27Kip1. Functional pathway dose-response analysis provides a unique opportunity to uncover nonmonotonic patterns in biological systems
Prevalence of diabetic retinopathy among 13473 patients with diabetes mellitus in China: a cross-sectional epidemiological survey in six provinces
Huibin Lv,Liyuan Tao,Mingzhou Zhang,Weiqiang Qiu,Xiaodan Jiang,Xuemin Li,Yan Liu,Yifan Song
- , 2017, DOI: 10.1136/bmjopen-2016-013199
Abstract: Objective To describe the prevalence and severity of diabetic retinopathy (DR) and sight-threatening DR (STDR) among Chinese adults with diabetes. Design, setting and participants A cross-sectional epidemiological survey across Mainland China (N=13？473). Participants were diagnosed with diabetes mellitus by physicians and transferred to our screening clinics (1/3 from hospital patients, 1/3 from city residents, the other 1/3 from rural residents). 2 fundus photographs were taken of each eye with a colourful, non-mydriatic and non-stereoscopic camera and were graded according to the UK guidelines. Main outcomes and measures The prevalence and severity of DR and STDR. Results Of the 13？473 participants with diabetes participating in the study, 4591 had DR and 1769 had STDR, for an overall prevalence of 34.08% (95% CI 33.28% to 34.88%) and 13.13% (95% CI 12.56% to 13.70%), respectively. Among these, gradable photographs were available for 12？780 participants (94.86%). Participants who were aged >65？years were less likely to suffer from DR or STDR (p<0.001; age distribution). No gender-related differences were present (p>0.05). Participants with STDR suffered from more severe visual impairment compared with those without STDR (p<0.001). The prevalence of DR and STDR in the northern region was higher than in the southern region (p<0.001). The prevalence of DR was closely related to duration of disease (OR 2.63; 95% CI 2.42 to 2.86; p<0.001) and diabetes onset age (OR 0.38; 95% CI 0.35 to 0.41; p<0.001). Conclusions The prevalence of DR and STDR in Mainland China appeared a little high, and varied according to area. Non-proliferative DR was more common, but STDR needed prompt treatment, especially in economically less developed areas. This study highlights the necessity for DR screening and treatment in Mainland China
Are the ASISA Standards with Respect to Unit Trust Classification Representative of Homogeneous Risk Classes?  [PDF]
Joe Kainja
Journal of Financial Risk Management (JFRM) , 2016, DOI: 10.4236/jfrm.2016.52008
Abstract: We examine the information content of South African (SA) equity unit trusts to investigate whether risk is heterogeneous between investment objective groups and homogeneous within groups because those characteristics are vital to proper investment decision making. We find risk differences within SA equity groups especially in the Equity-General and Equity-Growth. However, in the other categories, the systematic risk differences depended on the choice of benchmark. Those risk differences may have significant implications for investors. Examination of between-group risk revealed that not all the equity categories were heterogeneous. We also find that the choice of benchmark is critical when measuring and comparing performance characteristics of funds.
Decomposing Neural Synchrony: Toward an Explanation for Near-Zero Phase-Lag in Cortical Oscillatory Networks
Rajasimhan Rajagovindan, Mingzhou Ding
PLOS ONE , 2008, DOI: 10.1371/journal.pone.0003649
Abstract: Background Synchronized oscillation in cortical networks has been suggested as a mechanism for diverse functions ranging from perceptual binding to memory formation to sensorimotor integration. Concomitant with synchronization is the occurrence of near-zero phase-lag often observed between network components. Recent theories have considered the importance of this phenomenon in establishing an effective communication framework among neuronal ensembles. Methodology/Principal Findings Two factors, among possibly others, can be hypothesized to contribute to the near-zero phase-lag relationship: (1) positively correlated common input with no significant relative time delay and (2) bidirectional interaction. Thus far, no empirical test of these hypotheses has been possible for lack of means to tease apart the specific causes underlying the observed synchrony. In this work simulation examples were first used to illustrate the ideas. A quantitative method that decomposes the statistical interdependence between two cortical areas into a feed-forward, a feed-back and a common-input component was then introduced and applied to test the hypotheses on multichannel local field potential recordings from two behaving monkeys. Conclusion/Significance The near-zero phase-lag phenomenon is important in the study of large-scale oscillatory networks. A rigorous mathematical theorem is used for the first time to empirically examine the factors that contribute to this phenomenon. Given the critical role that oscillatory activity is likely to play in the regulation of biological processes at all levels, the significance of the proposed method may extend beyond systems neuroscience, the level at which the present analysis is conceived and performed.
Epigenetic changes in colorectal cancer
Yan Jia,Mingzhou Guo
Chinese Journal of Cancer , 2013, DOI: 10.5732/cjc.011.10245
Abstract: Epigenetic changes frequently occur in human colorectal cancer. Genomic global hypomethylation, gene promoter region hypermethylation, histone modifications, and alteration of miRNA patterns are major epigenetic changes in colorectal cancer. Loss of imprinting(LOI) is associated with colorectal neoplasia. Folate deficiency may cause colorectal carcinogenesis by inducing gene-specific hypermethylation and genomic global hypomethylation. HDAC inhibitors and demethylating agents have been approved by the FDA for myelodysplastic syndrome and leukemia treatment. Non-coding RNA is regarded as another kind of epigenetic marker in colorectal cancer. This review is mainly focused on DNA methylation, histone modification, and microRNA changes in colorectal cancer.
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