DARDN: A Deep-Learning Approach for CTCF Binding Sequence Classification and Oncogenic Regulatory Feature Discovery.

Characterization of gene regulatory mechanisms in cancer is a key task in cancer genomics. CCCTC-binding factor (CTCF), a DNA binding protein, exhibits specific binding patterns in the genome of cancer cells and has a non-canonical function to facilitate oncogenic transcription programs by cooperating with transcription factors bound at flanking distal regions. Identification of DNA sequence features from a broad genomic region that distinguish cancer-specific CTCF binding sites from regular CTCF binding sites can help find oncogenic transcription factors in a cancer type. However, the presence of long DNA sequences without localization information makes it difficult to perform conventional motif analysis. Here, we present DNAResDualNet (DARDN), a computational method that utilizes convolutional neural networks (CNNs) for predicting cancer-specific CTCF binding sites from long DNA sequences and employs DeepLIFT, a method for interpretability of deep learning models that explains the model's output in terms of the contributions of its input features. The method is used for identifying DNA sequence features associated with cancer-specific CTCF binding. Evaluation on DNA sequences associated with CTCF binding sites in T-cell acute lymphoblastic leukemia (T-ALL) and other cancer types demonstrates DARDN's ability in classifying DNA sequences surrounding cancer-specific CTCF binding from control constitutive CTCF binding and identifying sequence motifs for transcription factors potentially active in each specific cancer type. We identify potential oncogenic transcription factors in T-ALL, acute myeloid leukemia (AML), breast cancer (BRCA), colorectal cancer (CRC), lung adenocarcinoma (LUAD), and prostate cancer (PRAD). Our work demonstrates the power of advanced machine learning and feature discovery approach in finding biologically meaningful information from complex high-throughput sequencing data.

Orthogonal Cationic and Radical RAFT Polymerizations to Prepare Bottlebrush Polymers.

An orthogonal combination of cationic and radical RAFT polymerizations is used to synthesize bottlebrush polymers using two distinct RAFT agents. Selective consumption of the first RAFT agent is used to control the cationic RAFT polymerization of a vinyl ether monomer bearing a secondary dormant RAFT agent, which subsequently allows side-chain polymers to be grafted from the pendant RAFT agent by a radical-mediated RAFT polymerization of a different monomer, thus completing the synthesis of bottlebrush polymers. The high efficiency and selectivity of the cationic and radical RAFT polymerizations allow both polymerizations to be conducted in one-pot tandem without intermediate purification.

A Thermodynamic Roadmap for the Grafting-through Polymerization of PDMS11MA.

Grafting-through atom transfer radical polymerization (ATRP) was used to polymerize a sterically hindered poly(dimethylsiloxane) methacrylate (PDMS11MA, Mn = 1000) macromonomer to high conversion as a function of temperature, solvent, initial monomer concentration, and pressure. Higher polymerization yields were obtained when polymerizations were conducted at (i) lower temperature (T), (ii) in a poor solvent for the side chain, (iii) higher initial monomer concentration ([M]0), and (iv) higher pressure by mitigating the contribution of the equilibrium monomer concentration ([M]eq). The enthalpy of polymerization (ΔHp) and entropy of polymerization (ΔSp) were more negative in poor solvents. Polymerizations at ambient pressure required higher [M]0, use of a poor solvent, and lower temperatures to reach higher conversion with good control, whereas high pressure ATRP (HP-ATRP) displayed better control under dilute conditions. Grafting-through polymerization at high P and higher [M]0 was less controlled, plausibly due to limited solubility and mobility of the copper catalyst in the highly viscous medium.

Strained Bottlebrushes in Super-Soft Physical Networks.

ABA triblock copolymers composed of a poly(dimethylsiloxane) (PDMS) bottlebrush central block and linear poly(methyl methacrylate) (PMMA) terminal blocks self-assemble into a physical network of PDMS bottlebrush strands connected by PMMA spherical domains. A combination of small- and ultrasmall-angle X-ray scattering techniques was used to concurrently examine dimensions of PMMA spherical domains and PDMS bottlebrush strands both in the bulk and at the PMMA-PDMS interface. In agreement with scaling model predictions, the degrees of polymerization of the bottlebrush backbone (nbb) and PMMA block (nA) correlate with the measured PMMA domain size and area per molecule at the PMMA-PDMS interface as DA ∝ (nbbnA)1/3 and S ∝ nA2/3nbb-1/3, respectively. In the bulk, bottlebrush strands are extended due to steric repulsion between the side chains and unfavorable interactions between the different blocks. At the PMMA-PDMS interface with large curvature, packing constraints require additional bottlebrush backbone extension and alignment of side chains along the backbone in the direction perpendicular to the interface.

Chameleon-like elastomers with molecularly encoded strain-adaptive stiffening and coloration.

Active camouflage is widely recognized as a soft-tissue feature, and yet the ability to integrate adaptive coloration and tissuelike mechanical properties into synthetic materials remains elusive. We provide a solution to this problem by uniting these functions in moldable elastomers through the self-assembly of linear-bottlebrush-linear triblock copolymers. Microphase separation of the architecturally distinct blocks results in physically cross-linked networks that display vibrant color, extreme softness, and intense strain stiffening on par with that of skin tissue. Each of these functional properties is regulated by the structure of one macromolecule, without the need for chemical cross-linking or additives. These materials remain stable under conditions characteristic of internal bodily environments and under ambient conditions, neither swelling in bodily fluids nor drying when exposed to air.