Comprehensive landscape of resistance mechanisms for neoadjuvant therapy in esophageal squamous cell carcinoma by single-cell transcriptomics

Dear Editor,Preoperative neoadjuvant therapy combined with surgical resection is the standard treatment for locally advanced esopha-geal squamous cell carcinoma(ESCC).However,more than half of patients having a partial response to neoadjuvant therapy,which is considered as a therapy-resistant phenotype and the mechan-ism is still unclear.The heterogeneity of the ESCC with surgery alone therapy were characterized by single-cell RNA sequencing(scRNA-seq)previously,but few report was about ESCC patients with neoadjuvant therapy.1 It is emergent to illustrate the comprehensive hallmarks of neoadjuvant therapy-resistance in ESCC at single cell level.

Exploring noncoding variants in genetic diseases:from detection to functional insights

Previous studies on genetic diseases predominantly focused on protein-coding variations, overlooking the vast noncoding regions in the human genome. The development of high-throughput sequencing technologies and functional genomics tools has enabled the systematic identification of functional noncoding variants. These variants can impact gene expression, regulation, and chromatin conformation, thereby contributing to disease pathogenesis. Understanding the mechanisms that underlie the impact of noncoding variants on genetic diseases is indispensable for the development of precisely targeted therapies and the implementation of personalized medicine strategies. The intricacies of noncoding regions introduce a multitude of challenges and research opportunities. In this review, we introduce a spectrum of noncoding variants involved in genetic diseases, along with research strategies and advanced technologies for their precise identification and in-depth understanding of the complexity of the noncoding genome. We will delve into the research challenges and propose potential solutions for unraveling the genetic basis of rare and complex diseases.

SmProt: A Reliable Repository with Comprehensive Annotation of Small Proteins Identified from Ribosome Profiling

Small proteins specifically refer to proteins consisting of less than 100 amino acids translated from small open reading frames(s ORFs),which were usually missed in previous genome annotation.The significance of small proteins has been revealed in current years,along with the discovery of their diverse functions.However,systematic annotation of small proteins is still insufficient.Sm Prot was specially developed to provide valuable information on small proteins for scientific community.Here we present the update of Sm Prot,which emphasizes reliability of translated s ORFs,genetic variants in translated s ORFs,disease-specific s ORF translation events or sequences,and remarkably increased data volume.More components such as non-ATG translation initiation,function,and new sources are also included.Sm Prot incorporated638,958 unique small proteins curated from 3,165,229 primary records,which were computationally predicted from 419 ribosome profiling(Ribo-seq)datasets or collected from literature and other sources from 370 cell lines or tissues in 8 species(Homo sapiens,Mus musculus,Rattus norvegicus,Drosophila melanogaster,Danio rerio,Saccharomyces cerevisiae,Caenorhabditis elegans,and Escherichia coli).In addition,small protein families identified from human microbiomes were also collected.All datasets in Sm Prot are free to access,and available for browse,search,and bulk downloads at http://bigdata.ibp.ac.cn/SmProt/.

Genomes of 12 fig wasps provide insights into the adaptation of pollinators to fig syconia

Figs and fig pollinators are one of the few classic textbook examples of obligate pollination mutualism.The specific dependence of fig pollinators on the relatively safe living environment with sufficient food sources in the enclosed fig syconia implies that they are vulnerable to habitat changes.However,there is still no extensive genomic evidence to reveal the evolutionary footprint of this long-term mutually beneficial symbiosis in fig pollinators.In fig syconia,there are also non-pollinator species.The non-pollinator species differ in their evolutionary and life histories from pollinators.We conducted comparative analyses on 11 newly sequenced fig wasp genomes and one previously published genome.The pollinators colonized the figs approximately 66.9 million years ago,consistent with the origin of host figs.Compared with nonpollinators,many more genes in pollinators were subject to relaxed selection.Seven genes were absent in pollinators in response to environmental stress and immune activation.Pollinators had more streamlined gene repertoires in the innate immune system,chemosensory toolbox,and detoxification system.Our results provide genomic evidence for the differentiation between pollinators and nonpollinators.The data suggest that owing to the long-term adaptation to the fig,some genes related to functions no longer required are absent in pollinators.