Aging, an extremely complex and system-level process, has attracted much attention in medical research, especially since chronic diseases are quite prevalent in the elderly population. These may be the result of both gene mutations that lead to intrinsic perturbations and environmental changes that may stimulate signaling in the body. Therefore, analysis of network robustness to tolerate intrinsic perturbations and network response ability of gene networks to respond to external stimuli during the aging process may provide insight into the systematic changes caused by aging. We first propose novel methods to estimate network robustness and measure network response ability of gene regulatory networks by using their corresponding microarray data in the aging process. Then, we find that an aging-related gene network is more robust to intrinsic perturbations in the elderly than the young, and therefore is less responsive to external stimuli. Finally, we find that the response abilities of individual genes, especially FOXOs, NF-κB, and p53, are significantly different in the young versus the aged subjects. These observations are consistent with experimental findings in the aged population, e.g., elevated incidence of tumorigenesis and diminished resistance to oxidative stress. The proposed method can also be used for exploring and analyzing the dynamic properties of other biological processes via corresponding microarray data to provide useful information on clinical strategy and drug target selection.

“Robustness”, the network ability to maintain systematic performance in the face of intrinsic perturbations, and “response ability”, the network ability to respond to external stimuli or transduce them to downstream regulators, are two important complementary system characteristics that must be considered when discussing biological system performance. However, at present, these features cannot be measured directly for all network components in an experimental procedure. Therefore, we present two novel systematic measurement methods – Network Robustness Measurement (NRM) and Response Ability Measurement (RAM) – to estimate the network robustness and response ability of a gene regulatory network (GRN) or protein-protein interaction network (PPIN) based on the dynamic network model constructed by the corresponding microarray data. We demonstrate the efficiency of NRM and RAM in analyzing GRNs and PPINs, respectively, by considering aging- and cancer-related datasets. When applied to an aging-related GRN, our results indicate that such a network is more robust to intrinsic perturbations in the elderly than in the young, and is therefore less responsive to external stimuli. When applied to a PPIN of fibroblast and HeLa cells, we observe that the network of cancer cells possesses better robustness than that of normal cells. Moreover, the response ability of the PPIN calculated from the cancer cells is lower than that from healthy cells. Accordingly, we propose that generalized NRM and RAM methods represent effective tools for exploring and analyzing different systems-level dynamical properties via microarray data. Making use of such properties can facilitate prediction and application, providing useful information on clinical strategy, drug target selection, and design specifications of synthetic biology from a systems biology perspective.

Motivation: Whole genome sequencing (WGS) by next-generation sequencing produces millions of variants for an individual. The retrieval of biomedical literature for such a large number of genetic variants remains challenging, because in many cases the variants are only present in tables as images, or in the supplementary documents of which the file formats are diverse. Results: The proposed tool named variant2literature from the TaiGenomics (Toolkits for AI genomics) resolves the problem by incorporating text recognition with image processing. In addition to the adoption of advanced text retrieval, the recall rate of finding the literature containing the variants of interest is further improved by employing the skill of variant normalization. Different variant presentations are transformed into chromosome coordinates (standard VCF format) such that false negatives can be largely avoided. variant2literature is available in two ways. First, a web-based interface is provided to search all the literature in PMC Open Access Subset. Second, the command-line executable can be downloaded such that the users are free to search all the files in a specified directory locally.

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