scDR: Predicting Drug Response at Single-Cell Resolution

Heterogeneity exists inter- and intratumorally, which might lead to different drug responses. Therefore, it is extremely important to clarify the drug response at single-cell resolution. Here, we propose a precise single-cell drug response (scDR) prediction method for single-cell RNA sequencing (scRNA-seq) data. We calculated a drug-response score (DRS) for each cell by integrating drug-response genes (DRGs) and gene expression in scRNA-seq data. Then, scDR was validated through internal and external transcriptomics data from bulk RNA-seq and scRNA-seq of cell lines or patient tissues. In addition, scDR could be used to predict prognoses for BLCA, PAAD, and STAD tumor samples. Next, comparison with the existing method using 53,502 cells from 198 cancer cell lines showed the higher accuracy of scDR. Finally, we identified an intrinsic resistant cell subgroup in melanoma, and explored the possible mechanisms, such as cell cycle activation, by applying scDR to time series scRNA-seq data of dabrafenib treatment. Altogether, scDR was a credible method for drug response prediction at single-cell resolution, and helpful in drug resistant mechanism exploration

The significant magnetic attenuation with submicrometer scale magnetic phase separation in tensile-strained LaCoO3 films

It is well known that the epitaxial strain plays a vital role in tuning the magnetic states in transition metal oxide LaCoO3 films. Here, we reported a robust long-range ferromagnetic (FM) ground state in a tensile-strained perovskite LaCoO3 film on a SrTiO3 (STO) substrate, which has a very significant attenuation when the thickness ranges from 10 to 50 nm. It is speculated that such attenuation may be caused by the appearance of the cross-hatched grain boundary, which relaxes the tensile strain around the crosshatch, resulting in the local non-FM phases. Magnetic force microscope observation reveals non-FM patterns correlated with the structural crosshatches in the strain-relaxed film even down to a temperature of 2 K and up to a magnetic field of 7 T, suggesting the phase separation origin of magnetization attenuation. Furthermore, the investigations of the temperature-dependent inverse magnetic susceptibility show a deviation from the Curie–Weiss law above the transition temperature in a 50-nm-thick LaCoO3/STO film but not in the LaCoO3/LaAlO3 film, which is ascribed to the Griffiths phase due to the crosshatch-line grain boundaries. These results demonstrated that the local strain effect due to structural defects is important to affect the ferromagnetism in strain-engineered LaCoO3 films, which may have potential implications for future oxide-based spintronics

1D-Reactor Decentralized MDA for Uniform and Accurate Whole Genome Amplification

Multiple displacement amplification (MDA), a most popular isothermal whole genome amplification (WGA) method, suffers the major hurdle of highly uneven amplification, thus, leading to many problems in approaching biological applications related to copy-number assessment. In addition to the optimization of reagents and conditions, complete physical separation of the entire reaction system into numerous tiny chambers or droplets using microfluidic devices, has been proven efficient to mitigate this amplifying bias in recent works. Here, we present another MDA advance, microchannel MDA (μcMDA), which decentralizes MDA reagents throughout a one-dimensional slender tube. Due to the double effect from soft partition of high molecular-weight DNA molecules and less-limited diffusion of small particles, μcMDA is shown to be significantly effective at improving the amplification uniformity, which enables us to accurately detect single nucleotide variants (SNVs) with higher efficiency and sensitivity. More importantly, this straightforward method requires neither customized instruments nor complicated operations, making it a ready-to-use technique in almost all biological laboratories