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The mechanisms of chronic pain are complex, and genetic factors play an essential role in the development of chronic pain. Neuropathic pain (NP) and inflammatory pain (IP) are two primary components of chronic pain. Previous studies have uncovered some common biological processes in NP and IP. However, the shared genetic mechanisms remained poorly studied. We utilized multi-omics systematic analyses to investigate the shared genetic mechanisms of NP and IP. First, by integrating several genome-wide association studies (GWASs) with multi-omics data, we revealed the significant overlap of the gene co-expression modules in NP and IP. Further, we uncovered the shared biological pathways, including the previously reported mitochondrial electron transport and ATP metabolism, and stressed the role of genetic factors in chronic pain with neurodegenerative diseases. Second, we identified 24 conservative key drivers (KDs) contributing to NP and IP, containing two well-established pain genes, IL1B and OPRM1, and some novel potential pain genes, such as C5AR1 and SERPINE1. The subnetwork of those KDs highlighted the processes involving the immune system. Finally, gene expression analysis of the KDs in mouse models underlined two of the KDs, SLC6A15 and KCNQ5, with unidirectional regulatory functions in NP and IP. Our study provides strong evidence to support the current understanding of the shared genetic regulatory networks underlying NP and IP and potentially benefit the future common therapeutic avenues for chronic pain.

In this paper, we explore the need to improve systems awareness to support early-phase decision-making. This research uses the Norwegian energy industry as context. This industry deals with highly complex engineering systems that shall operate remotely for 25+ years. Through an in-depth study in a systems supplier company, we find that engineers are not sufficiently aware of the systems operational context and do not focus on the context in the early phase. We identified the lack of a holistic mindset and the challenge of balancing internal strategy and customers’ needs as the prevalent barriers. To support the concept evaluation, the subsea system suppliers need to raise systems awareness in the early phase. The study identifies four aspects that are important to consider when developing and implementing approaches to improve systems awareness in the early phase.

The insulin-like growth factors (IGFs)/insulin resistance (IR) axis is the major metabolic hormonal pathway mediating the biologic mechanism of several complex human diseases, including type 2 diabetes (T2DM) and cancers. The genomewide association study (GWAS)-based approach has neither fully characterized the phenotype variation nor provided a comprehensive understanding of the regulatory biologic mechanisms. We applied systematic genomics to integrate our previous GWAS data for IGF-I and IR with multi-omics datasets, e.g., whole-blood expression quantitative loci, molecular pathways, and gene network, to capture the full range of genetic functionalities associated with IGF-I/IR and key drivers (KDs) in gene-regulatory networks. We identified both shared (e.g., T2DM, lipid metabolism, and estimated glomerular filtration signaling) and IR-specific (e.g., mechanistic target of rapamycin, phosphoinositide 3-kinases, and erb-b2 receptor tyrosine kinase 4 signaling) molecular biologic processes of IGF-I/IR axis regulation. Next, by using tissue-specific gene–gene interaction networks, we identified both well-established (e.g., IRS1 and IGF1R) and novel (e.g., AKT1, HRAS, and JAK1) KDs in the IGF-I/IR-associated subnetworks. Our results, if validated in additional genomic studies, may provide robust, comprehensive insights into the mechanisms of IGF-I/IR regulation and highlight potential novel genetic targets as preventive and therapeutic strategies for the associated diseases, e.g., T2DM and cancers.