Boundless Bio, Inc. (BB), and serve as consultants. V.B. is a co-founder, and has equity interest in Boundless Bio, inc. (BB) and Digital Proteomics, LLC (DP), and receives income from DP. The terms of this arrangement have been reviewed and approved by the University of California, San Diego in accordance with its conflict of interest policies. BB and DP were not involved in the research presented here. Data Availability. Whole genome-, RNA-, ATAC-, MNase-, ChIP-, PLAC-Seq data are deposited in the NCBI Sequence Read Archive (BioProject: PRJNA506071). The source data files of the pixel quantification of ATAC-see on metaphase chromosome spread images to create Extended Data Figure 7d are available on Figshare (

Extrachromosomal DNA (ecDNA) amplification promotes intratumoral genetic heterogeneity and accelerated tumor evolution 1 – 3 , but its frequency and clinical impact are unclear. Here we show, using computational analysis of whole-genome sequencing data from 3,212 cancer patients, that ecDNA amplification frequently occurs in most cancer types, but not in blood or normal tissue. Oncogenes were highly enriched on amplified ecDNA and the most common recurrent oncogene amplifications arise on ecDNA. EcDNA amplifications resulted in higher levels of oncogene transcription compared to copy number matched linear DNA, coupled with enhanced chromatin accessibility and more frequently resulted in transcript fusions. Patients whose cancers carry ecDNAs have significantly shorter survival, even when controlled for tissue type, than do patients whose cancers are not driven by ecDNA-based oncogene amplification. The results presented here demonstrate that ecDNA-based oncogene amplification is common in cancer, is different from chromosomal amplification and drives poor outcome for patients across many cancer types.

Crop breeding aims to balance disease resistance with yield; however, single resistance (R) genes can lead to resistance breakdown, and R gene pyramiding may affect growth fitness. Here we report that the rice locus contains a cluster of genes encoding nucleotide-binding leucine-rich repeat (NLR) receptors that confer durable resistance to the fungus without yield penalty. Among these NLR receptors, PigmR confers broad-spectrum resistance, whereas PigmS competitively attenuates PigmR homodimerization to suppress resistance. expression, and thus-mediated resistance, are subjected to tight epigenetic regulation. increases seed production to counteract the yield cost induced by Therefore, our study reveals a mechanism balancing high disease resistance and yield through epigenetic regulation of paired antagonistic NLR receptors, providing a tool to develop elite crop varieties.

This article reports on a noninvasive approach in detecting and following-up individuals who are at-risk or have an existing COVID-19 infection, with a potential ability to serve as an epidemic control tool. The proposed method uses a developed breath device composed of a nanomaterial-based hybrid sensor array with multiplexed detection capabilities that can detect disease-specific biomarkers from exhaled breath, thus enabling rapid and accurate diagnosis. An exploratory clinical study with this approach was examined in Wuhan, China, during March 2020. The study cohort included 49 confirmed COVID-19 patients, 58 healthy controls, and 33 non-COVID lung infection controls. When applicable, positive COVID-19 patients were sampled twice: during the active disease and after recovery. Discriminant analysis of the obtained signals from the nanomaterial-based sensors achieved very good test discriminations between the different groups. The training and test set data exhibited respectively 94% and 76% accuracy in differentiating patients from controls as well as 90% and 95% accuracy in differentiating between patients with COVID-19 and patients with other lung infections. While further validation studies are needed, the results may serve as a base for technology that would lead to a reduction in the number of unneeded confirmatory tests and lower the burden on hospitals, while allowing individuals a screening solution that can be performed in PoC facilities. The proposed method can be considered as a platform that could be applied for any other disease infection with proper modifications to the artificial intelligence and would therefore be available to serve as a diagnostic tool in case of a new disease outbreak.