Genomics, Proteomics & Bioinformatics

Over the past 20 years, tremendous advances in sequencing technologies and computational algorithms have spurred plant genomic research into a thriving era with hundreds of genomes decoded already, ranging from those of nonvascular plants to those of flowering plants. However, complex genome assembly is still challenging and remains difficult to fully resolve with conventional sequencing and assembly methods due to the high heterozygosity, repetitive sequences, or high ploidy characteristics of complex genomes...

The gut microbiome is closely related to host nutrition and health. However, the relationships between gut microorganisms and host lifestyle are not well characterized. In the absence of confounding geographic variation, we defined clear patterns of variation in the gut microbiomes of Asian elephants (AEs) in the Wild Elephant Valley, Xishuangbanna, China, along a lifestyle gradient (fully captive, semicaptive, semiwild, and purely wild). A phylogenetic analysis using the 16S rRNA gene sequences highlighted that the microbial diversity decreased as the degree of captivity increased...

The recently developed technologies that allow the analysis of each single omics have provided an unbiased insight into ongoing disease processes. However, it remains challenging to specify the study design for the subsequent integration strategies that can associate sepsis pathophysiology and clinical outcomes. Here, we conducted a time-dependent multi-omics integration (TDMI) in a sepsis-associated liver dysfunction (SALD) model. We successfully deduced the relation of the toll-like receptor (TLR4) pathway with SALD...

During mammalian preimplantation development, a totipotent zygote undergoes several cell cleavages and two rounds of cell fate determination, ultimately forming a mature blastocyst. Along with compaction, the establishment of apico-basal cell polarity breaks the symmetry of an embryo and guides subsequent cell fate choice. Although the lineage segregation of the inner cell mass (ICM) and trophectoderm (TE) is the first symbol of cell differentiation, several molecules have been shown to bias the early cell fate through their inter-cellular variations at much earlier stages, including the 2- and 4-cell stages...

As one of the state-of-the-art automated function prediction (AFP) methods, NetGO 2.0 integrates multi-source information to improve the performance. However, it mainly utilizes the proteins with experimentally supported functional annotations without leveraging valuable information from a vast number of unannotated proteins. Recently, protein language models have been proposed to learn informative representations [e.g., Evolutionary Scale Modelling (ESM)-1b embedding] from protein sequences based on self-supervision...

Identifying genetic risk factors for Alzheimer's disease (AD) is an important research topic. To date, different endophenotypes, such as imaging-derived endophenotypes and proteomic expression-derived endophenotypes, have shown the great value in uncovering risk genes compared to case-control studies. Biologically, a co-varying pattern of different omics-derived endophenotypes could result from the shared genetic basis. However, existing methods mainly focus on the effect of endophenotypes alone; the effect of cross-endophenotype (CEP) associations remains largely unexploited...

Protein structure prediction is an interdisciplinary research topic that has attracted researchers from multiple fields, including biochemistry, medicine, physics, mathematics, and computer science. These researchers adopt various research paradigms to attack the same structure prediction problem: biochemists and physicists attempt to reveal the principles governing protein folding; mathematicians, especially statisticians, usually start from assuming a probability distribution of protein structures given a target sequence and then find the most likely structure; while computer scientists formulate protein structure prediction as an optimization problem - finding the structural conformation with the lowest energy, or minimizing the difference between predicted structure and native structure...

Circular RNAs (circRNAs) are endogenous non-coding RNAs with covalently closed structures, which have important functions in plants. However, their biogenesis, degradation, and function upon treatment with gibberellins (GAs) and auxins (1-Naphthaleneacetic acid, NAA) remain unknown. Here, we systematically identified and characterized expression patterns, evolutionary conservation, genomic features, and internal structures of circRNAs using RNase R-treated libraries from moso bamboo (Phyllostachys edulis) seedlings...

Integration of oncogenic DNA viruses into the human genome is a key step in most virus-induced carcinogenesis. Here, we constructed virus integration site (VIS) Atlas database, an extensive collection of integration breakpoints for three most prevalent oncoviruses, human papillomavirus (HPV), hepatitis B virus (HBV), and Epstein-Barr virus (EBV) based on next-generation sequencing (NGS) data, literature, and experimental data. There are 63,179 breakpoints and 47,411 junctional sequences with full annotations deposited in VIS Atlas database, comprising 47 virus genotypes and 17 disease types...

The epitranscriptomic mark N6 -methyladenosine (m6 A), which is the predominant internal modification in RNAs, is important for plant responses to diverse stresses. Multiple environmental stresses caused by the tea-withering process can greatly influence the accumulation of specialized metabolites and the formation of tea flavor. However, the effects of the m6 A-mediated regulatory mechanism on flavor-related metabolic pathways in tea leaves remain relatively uncharacterized. We performed an integrated RNA methylome and transcriptome analysis to explore the m6 A-mediated regulatory mechanism and its effects on flavonoid and terpenoid metabolism under solar-withering conditions...

Defects in genes involved in the DNA damage response cause homologous recombination repair deficiency (HRD). HRD is found in a subgroup of patients with cancer with several tumor types, and it has a clinical relevance in cancer prevention and therapies. Accumulating evidence has identified HRD as a biomarker for assessing the therapeutic response of tumor cells to poly (ADP-ribose) polymerase inhibitors and platinum-based chemotherapies. Nevertheless, the biology of HRD is complex, and its applications and the benefits of different HRD biomarker assays are controversial...

Cyclocarya paliurus is a relict plant species that survived the last glacial period and shows a population expansion recently. Its leaves have been traditionally used to treat obesity and diabetes with the well-known active ingredient cyclocaric acid B (CA-B). Here, we present three C. paliurus genomes from two diploids with different flower morphs and one haplotype-resolved tetraploid assembly. Comparative genomic analysis revealed two rounds of recent whole-genome duplication events and identified 691 genes with dosage-effect that likely contribute to adaptive evolution through enhanced photosynthesis and increased accumulation of triterpenoids...

Prediction of the response of cancer patients to different treatments and identification of biomarkers of drug response are two major goals of individualized medicine. Here, we developed a deep learning framework called TINDL, completely trained on preclinical cancer cell lines (CCLs), to predict the response of cancer patients to different treatments. TINDL utilizes a tissue-informed normalization to account for the tissue type and cancer type of the tumors and to reduce the statistical discrepancies between CCLs and patient tumors...

Transcriptome analysis based on high-throughput sequencing of a cDNA library has been widely applied for functional genomic studies. However, the cDNA dependence of most RNA sequencing techniques constrains their ability to detect base modifications on RNA, which is an important element for the post-transcriptional regulation of gene expression. To comprehensively profile the N6 -methyladenosine (m6 A) and N5 -methylcytosine (m5 C) modifications on RNA, direct RNA sequencing (DRS) using the latest Oxford Nanopore Technology was applied to analyze the transcriptome of six tissues in rice...

Genomics, an interdisciplinary field of biology on the structure, function, and evolution of genomes, has revolutionized many subdisciplines of life sciences, including my field of evolutionary biology, by supplying huge data, bringing high-throughput technologies, and offering a new approach to biology. In this review, I describe what I have learned from genomics and highlight the fundamental knowledge and mechanistic insights gained. I focus on three broad topics that are central to evolutionary biology and beyond-variation, interaction, and selection-and use primarily my own research and study subjects as examples...

Adenosine-to-inosine (A-to-I) RNA editing, constituting nearly 90% of all RNA editing events in humans, has been reported to contribute to the tumorigenesis in diverse cancers. However, the comprehensive map for functional A-to-I RNA editing events in cancers is still insufficient. To fill this gap, we systematically and intensively analyzed multiple tumorigenic mechanisms of A-to-I RNA editing events in samples across 33 cancer types from The Cancer Genome Atlas. For individual candidate among ∼ 1.5 M quantified RNA editing events, we performed diverse types of down-stream functional annotations...

Studies on the lung cancer genome are indispensable for developing a cure for lung cancer. Whole-genome resequencing, genome-wide association studies, and transcriptome sequencing have greatly improved our understanding of the cancer genome. However, dysregulation of long-range chromatin interactions in lung cancer remains poorly described. To better understand the three-dimensional (3D) genomic interaction features of the lung cancer genome, we used the A549 cell line as a model system and generated high-resolution chromatin interactions associated with RNA polymerase II (RNAPII), CCCTC-binding factor (CTCF), enhancer of zeste homolog 2 (EZH2), and histone 3 lysine 27 trimethylation (H3K27me3) using long-read chromatin interaction analysis by paired-end tag sequencing (ChIA-PET)...

Alternative polyadenylation (APA) contributes to transcriptome complexity and gene expression regulation and has been implicated in various cellular processes and diseases. Single-cell RNA sequencing (scRNA-seq) has enabled the profiling of APA at the single-cell level; however, the spatial information of cells is not preserved in scRNA-seq. Alternatively, spatial transcriptomics (ST) technologies provide opportunities to decipher the spatial context of the transcriptomic landscape. Pioneering studies have revealed potential spatially variable genes and/or splice isoforms; however, the pattern of APA usage in spatial contexts remains unappreciated...

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Organs-on-a-chip is a microfluidic microphysiological system that uses microfluidic technology to analyze the structure and function of living human cells at the tissue and organ levels in vitro. Organs-on-a-chip technology, as opposed to traditional two-dimensional cell culture and animal models, can more closely simulate pathologic and toxicologic interactions between different organs or tissues and reflect the collaborative response of multiple organs to drugs. Despite the fact that many organs-on-a-chip-related data have been published, none of the current databases have all of the following functions: searching, downloading, and analyzing data and results from the literature on organs-on-a-chip...