Gene Regulatory Networks: A Primer in Biological Processes and Statistical Modelling

Unexpected links reflect the noise in networks

10.1101/000497 ◽

2013 ◽

Author(s):

Anatoly Yambartsev ◽

Michael Perlin ◽

Yevgeniy Kovchegov ◽

Natalia Shulzhenko ◽

Karina Mine ◽

...

Keyword(s):

Gene Regulatory Networks ◽

Regulatory Networks ◽

Molecular Mechanisms ◽

Simulation Analysis ◽

Biological Processes ◽

Special Relationship ◽

False Discovery ◽

Precise Estimation ◽

Gene Regulatory ◽

The Mathematical Model

Gene regulatory networks are commonly used for modeling biological processes and revealing underlying molecular mechanisms. The reconstruction of gene regulatory networks from observational data is a challenging task, especially, considering the large number of involved players (e.g. genes) and much fewer biological replicates available for analysis. Herein, we proposed a new statistical method of estimating the number of erroneous edges that strongly enhances the commonly used inference approaches. This method is based on special relationship between correlation and causality, and allows to identify and to remove approximately half of erroneous edges. Using the mathematical model of Bayesian networks and positive correlation inequalities we established a mathematical foundation for our method. Analyzing real biological datasets, we found a strong correlation between the results of our method and the commonly used false discovery rate (FDR) technique. Furthermore, the simulation analysis demonstrates that in large networks, our new method provides a more precise estimation of the proportion of erroneous links than FDR.

Download Full-text

Prioritizing candidate disease-related long non-coding RNAs by walking on the heterogeneous lncRNA and disease network

Molecular BioSystems ◽

10.1039/c4mb00511b ◽

2015 ◽

Vol 11 (3) ◽

pp. 760-769 ◽

Cited By ~ 109

Author(s):

Meng Zhou ◽

Xiaojun Wang ◽

Jiawei Li ◽

Dapeng Hao ◽

Zhenzhen Wang ◽

...

Keyword(s):

Gene Regulatory Networks ◽

Regulatory Networks ◽

Biological Processes ◽

Disease Network ◽

Wide Range ◽

Gene Regulatory ◽

Non Coding Rnas

Accumulated evidence has shown that long non-coding RNAs (lncRNA) act as a widespread layer in gene regulatory networks and are involved in a wide range of biological processes.

Download Full-text

Evolution and multiple roles of the Pancrustacea specific transcription factor zelda in insects

10.1101/126417 ◽

2017 ◽

Author(s):

Lupis Ribeiro ◽

Vitória Tobias-Santos ◽

Danielle Santos ◽

Felipe Antunes ◽

Geórgia Feltran ◽

...

Keyword(s):

Transcription Factor ◽

Gene Regulatory Networks ◽

Regulatory Networks ◽

Chromatin Accessibility ◽

Multiple Roles ◽

Biological Processes ◽

Regulatory Modules ◽

Ancestral Function ◽

Gene Regulatory ◽

Whole Egg

SummaryGene regulatory networks (GRN) evolve as a result of the coevolutionary process acting on transcription factors and the cis-regulatory modules (CRMs) they bind. The zinc-finger transcription factor (TF) zelda (zld) is essential for maternal zygotic transition (MZT) in Drosophila melanogaster, where it directly binds over thousand CRMs to regulate chromatin accessibility. D. melanogaster displays a long germ type of embryonic development, where all segments are simultaneously generated along the whole egg. However, it remains unclear if zld is also involved in MZT of short-germ insects (including those from basal lineages) or in other biological processes. Here we show that zld is an innovation of the Pancrustacea lineage, being absent in more distant arthropods (e.g. chelicerates) and other organisms. To better understand zld’s ancestral function, we thoroughly investigated its roles in a short-germ beetle, Tribolium castaneum, using molecular biology and computational approaches. Our results demonstrate roles for zld not only during the MZT, but also in posterior segmentation and patterning of imaginal disc derived structures. Further, we also demonstrate that zld is critical for posterior segmentation in the hemipteran Rhodnius prolixus, indicating this function predates the origin of holometabolous insects and was subsequently lost in long-germ insects. Our results unveil new roles of zld in maintaining pluripotent state of progenitor cells at the posterior region and suggest that changes in expression of zld (and probably other pioneer TFs) are critical in the evolution of insect GRNs.

Download Full-text