Background: The distribution of isoelectric point (pI) of proteins in a proteome is universal for all organisms. It is bimodal dividing the proteome into two sets of acidic and basic proteins. Different species however have different abundance of acidic and basic proteins that may be correlated with taxonomy, subcellular localization, ecological niche of organisms and proteome size.

Explainable Artificial Intelligence (xAI) is an established field with a vibrant community that has developed a variety of very successful approaches to explain and interpret predictions of complex machine learning models such as deep neural networks. In this article, we briefly introduce a few selected methods and discuss them in a short, clear and concise way. The goal of this article is to give beginners, especially application engineers and data scientists, a quick overview of the state of the art in this current topic. The following 17 methods are covered in this chapter: LIME, Anchors, GraphLIME, LRP, DTD, PDA, TCAV, XGNN, SHAP, ASV, Break-Down, Shapley Flow, Textual Explanations of Visual Models, Integrated Gradients, Causal Models, Meaningful Perturbations, and X-NeSyL.

SummaryReprogramming to induced pluripotent stem cells (iPSCs) and differentiation of pluripotent stem cells (PSCs) are regulated by epigenetic machinery. Tripartite motif protein 28 (TRIM28), a universal mediator of Krüppel-associated box domain zinc fingers (KRAB-ZNFs), is known to regulate both processes; however, the exact mechanism and identity of participating KRAB-ZNF genes remain unknown. Here, using a reporter system, we show that TRIM28/KRAB-ZNFs alter DNA methylation patterns in addition to H3K9me3 to cause stable gene repression during reprogramming. Using several expression datasets, we identified KRAB-ZNFs (ZNF114, ZNF483, ZNF589) in the human genome that maintain pluripotency. Moreover, we identified target genes repressed by these KRAB-ZNFs. Mechanistically, we demonstrated that these KRAB-ZNFs directly alter gene expression of important developmental genes by modulating H3K9me3 and DNA methylation of their promoters. In summary, TRIM28 employs KRAB-ZNFs to evoke epigenetic silencing of its target differentiation genes via H3K9me3 and DNA methylation.