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SummaryStructural features of proteins capture underlying information about protein evolution and function, which enhances the analysis of proteomic and transcriptomic data. Here we developStructuralAnalysis ofGene and proteinExpressionSignatures (SAGES), a method that describes expression data using features calculated from sequence-based prediction methods and 3D structural models. We used SAGES, along with machine learning, to characterize tissues from healthy individuals and those with breast cancer. We analyzed gene expression data from 23 breast cancer patients and genetic mutation data from the COSMIC database as well as 17 breast tumor protein expression profiles. We identified prominent expression of intrinsically disordered regions in breast cancer proteins as well as relationships between drug perturbation signatures and breast cancer disease signatures. Our results suggest that SAGES is generally applicable to describe diverse biological phenomena including disease states and drug effects.

One of the greatest challenges in synthetic chemistry is the development of reactions that can efficiently afford target compounds without creating byproducts. One such class of reactions are [2+2+2] cycloadditions. Here, three unsaturated coupling partners are combined to create six-membered rings, often with high regioselectivity, high yield, and no byproducts (i.e., secondary products). To further increase the attractiveness of these reactions, iron, a cheap and abundant catalyst, can be used. However, for the [2+2+2] synthesis of pyridines, a very important class of compounds, iron has traditionally been a very poor catalyst. By tethering unreactive nitriles to the more reactive alkynes, the first general iron-catalyzed [2+2+2] method to synthesize pyridines has been developed. This reactivity was further explored with the cycloaddition of diynes and cyanamides. Cyanamides demonstrated remarkable chemo- and regioselectivity. The three-component cycloaddition of terminal alkynes and a cyanamide could be performed with high yield and complete chemoselectivity. By combining aforementioned strategies of nitrile incorporation, the entirely novel cycloaddition of alkynenitriles and cyanamides has been developed. In this case, iron demonstrated reactivity that few [2+2+2] cycloaddition catalyst exhibited by incorporating multiple nitrogen atoms into the resulting 6-membered ring. Finally, isolation of presumed inorganic and organometallic intermediates provides a preliminary understanding of the mechanistic sequences involved in these iron-catalyzed [2+2+2] cycloadditions.