Virtual Gene Concept and a Corresponding Pragmatic Research Program in Genetical Data Science

Mendel proposed an experimentally verifiable paradigm of particle-based heredity that has been influential for over 150 years. The historical arguments have been reflected in the near past as Mendel’s concept has been diversified by new types of omics data. As an effect of the accumulation of omics data, a virtual gene concept forms, giving rise to genetical data science. The concept integrates genetical, functional, and molecular features of the Mendelian paradigm. I argue that the virtual gene concept should be deployed pragmatically. Indeed, the concept has already inspired a practical research program related to systems genetics. The program includes questions about functionality of structural and categorical gene variants, about regulation of gene expression, and about roles of epigenetic modifications. The methodology of the program includes bioinformatics, machine learning, and deep learning. Education, funding, careers, standards, benchmarks, and tools to monitor research progress should be provided to support the research program.

Duesselpore: a full-stack local web server for rapid and simple analysis of Oxford Nanopore Sequencing data

Genome-wide analysis of transcriptomes offers extensive insights into the molecular mechanisms underlying the physiology of all known species and discover those that are still hidden. Oxford Nanopore Technologies (ONT) has recently been developed as a fast, miniaturized, portable and a cost effective alternative to Next Generation Sequencing. However, RNA-seq data analysis software that exploit ONT portability and allows scientists to easily analyze ONT data everywhere without bioinformatic expertise is not widely available. We developed DuesselporeTM, an easy-to-follow deep sequencing workflow that runs as a local webserver and allows the analysis of ONT data everywhere without requiring additional bioinformatic tools or internet connection. DuesselporeTM output includes differentially expressed genes and further downstream analyses, such as variance heatmap, disease and gene ontology plots, gene concept network plots and exports customized pathways for different cellular processes. We validated DuesselporeTM by analyzing the transcriptomic changes induced by PCB126, a dioxin-like PCB and a potent aryl hydrocarbon receptor (AhR) agonist in human HaCaT keratinocytes, a well characterized model system. DuesselporeTM was specifically developed to analyze ONT data but we also implemented NGS data analysis. DuesselporeTM is compatible with Microsoft and Mac operating systems, allows convenient, reliable and cost-effective analysis of ONT and NGS data.

A Novel Mechanism of Action of Histone Deacetylase Inhibitor Chidamide: Enhancing the Chemotaxis Function of Circulating PD-1(+) Cells From Patients With PTCL

BackgroundPeripheral T‐cell lymphomas (PTCLs) are a heterogeneous group of neoplasms characterized by a poor prognosis. Histone deacetylase (HDAC) inhibitors have emerged as novel therapeutic agents for PTCLs. In this study, we aimed to explore the immunomodulatory effect of the HDAC inhibitor chidamide on circulating PD-1(+) cells from patients with PTCL, as well as its correlation with treatment response.MethodsWe enrolled newly diagnosed patients with PTCLs treated with a combination of chidamide and chemotherapy. Gene expression profile analysis was performed on peripheral blood PD-1(+) cells, both at baseline and at the end of treatment. A list of differentially expressed genes (DEGs) was identified. Gene Ontology (GO) and Kyoto Encyclopedia of Genes and Genomes (KEGG) pathway analyses were performed to annotate the biological implications of the DEGs. A gene concept network was constructed to identify the key DEGs for further PCR verification.ResultsA total of 302 DEGs were identified in the complete remission (CR) group, including 162 upregulated and 140 downregulated genes. In contrast, only 12 DEGs were identified in the non-CR group. GO analysis revealed that these upregulated DEGs were mainly involved in chemokine activity, cell chemotaxis, and cellular response to interleukin-1 and interferon-γ. Furthermore, KEGG pathway analysis showed that these DEGs were enriched in cytokine-cytokine receptor interaction and chemokine signaling pathways. The innate immune signaling pathways, including the Toll-like and NOD-like receptor signaling pathways, were also influenced. The gene concept network revealed that the key upregulated genes belonged to the C-C chemokine family.ConclusionOur results showed that chidamide treatment notably enhanced the expression of genes associated with chemokine activity and chemotaxis function of circulating PD-1(+) cells. By recruiting immune cells and improving the innate immune function of PD-1(+) cells, chidamide may reshape the tumor microenvironment to an anti-tumor phenotype and synergize with checkpoint inhibitors.

Ask Not “What Is an Individual?”

Philosophers of biology typically pose questions about individuation by asking “what is an individual?” For example, we ask: what is a species, what is an organism, and what is a gene? In this chapter, the author presents his account of the gene concept to motivate a more pragmatic approach. Instead of asking “what is a gene?,” he asks, “how do biologists individuate genes?,” “for what purposes?,” and “do their practices of individuating genes serve these purposes?” He proposes that philosophers use this approach when analyzing concepts of organisms and biological individuals. Following philosophical pragmatism, he argues that philosophers should view practices of individuating organisms in terms of a three-place relation: between the world, ideas, and human purposes and actions. He concludes with three lessons: an ontological, an epistemological, and a meta-philosophical lesson, which he suggests apply to philosophy of science generally and to philosophy and metaphysics at large.