Cell2Chem: mining explored and unexplored biosynthetic chemical spaces.

Summary: Living cell strains have important applications in synthesizing their native compounds and potential for use in studies exploring the universal chemical space. Here, we present a web server named as Cell2Chem which accelerates the search for explored compounds in organisms, facilitating investigations of biosynthesis in unexplored chemical spaces. Cell2Chem uses co-occurrence networks and natural language processing to provide a systematic method for linking living organisms to biosynthesized compounds and the processes that produce these compounds.

An in situ approach to characterizing photosynthetic gas exchange of rice panicle.

Background: Photosynthesis of reproductive organs in C cereals is generally regarded as important to crop yield. Whereas, photosynthetic characteristics of reproductive organs are much less understood as compared to leaf photosynthesis, mainly due to methodological limitations. To date, many indirect methods have been developed to study photosynthesis of reproductive organs and its contribution to grain yield, such as organ shading, application of herbicides and photosynthetic measurement of excised organs or tissues, which might be intrusive and cause biases.

Trnp1 organizes diverse nuclear membrane-less compartments in neural stem cells.

TMF1-regulated nuclear protein 1 (Trnp1) has been shown to exert potent roles in neural development affecting neural stem cell self-renewal and brain folding, but its molecular function in the nucleus is still unknown. Here, we show that Trnp1 is a low complexity protein with the capacity to phase separate. Trnp1 interacts with factors located in several nuclear membrane-less organelles, the nucleolus, nuclear speckles, and condensed chromatin.

Prognostic prediction of carcinoma by a differential-regulatory-network-embedded deep neural network.

The accurate prognostic prediction is essential for precise diagnosis and treatment of carcinoma. In addition to clinical survival prediction method, many computational methods based on transcriptomic data have been proposed to build the prediction models and study the prognosis of cancer patients. We propose a differential-regulatory-network-embedded deep neural network (DRE-DNN) method by integrating differential regulatory analysis based on gene co-expression network and deep neural network (DNN) method.

A Tale of Two Moieties: Rapidly Evolving CRISPR/Cas-Based Genome Editing.

Two major moieties in genome editing are required for precise genetic changes: the locator moiety for target binding and the effector moiety for genetic engineering. By taking advantage of CRISPR/Cas, which consists of different modules for independent target binding and cleavage, a spectrum of precise and versatile genome editing technologies have been developed for broad applications in biomedical research, biotechnology, and therapeutics. Here, we briefly summarize the progress of genome editing systems from a view of both locator and effector moieties and highlight the advance of newly reported CRISPR-conjugated base editing and prime editing systems.

A comparison of epigenetic mitotic-like clocks for cancer risk prediction.

Background: DNA methylation changes that accrue in the stem cell pool of an adult tissue in line with the cumulative number of cell divisions may contribute to the observed variation in cancer risk among tissues and individuals. Thus, the construction of epigenetic "mitotic" clocks that can measure the lifetime number of stem cell divisions is of paramount interest.

Methods: Building upon a dynamic model of DNA methylation gain in unmethylated CpG-rich regions, we here derive a novel mitotic clock ("epiTOC2") that can directly estimate the cumulative number of stem cell divisions in a tissue.

Nanopore Targeted Sequencing for the Accurate and Comprehensive Detection of SARS-CoV-2 and Other Respiratory Viruses.

The ongoing global novel coronavirus pneumonia COVID-19 outbreak has engendered numerous cases of infection and death. COVID-19 diagnosis relies upon nucleic acid detection; however, currently recommended methods exhibit high false-negative rates and are unable to identify other respiratory virus infections, thereby resulting in patient misdiagnosis and impeding epidemic containment. Combining the advantages of targeted amplification and long-read, real-time nanopore sequencing, herein, nanopore targeted sequencing (NTS) is developed to detect SARS-CoV-2 and other respiratory viruses simultaneously within 6-10 h, with a limit of detection of ten standard plasmid copies per reaction.

Lipidome analysis of milk composition in humans, monkeys, bovids, and pigs.

Background: Lipids contained in milk are an essential source of energy and structural materials for a growing neonate. Furthermore, lipids' long-chain unsaturated fatty acid residues can directly participate in neonatal tissue formation. Here, we used untargeted mass spectrometric measurements to assess milk lipid composition in seven mammalian species: humans, two macaque species, cows, goats, yaks, and pigs.

Individual variation of the SARS-CoV-2 receptor ACE2 gene expression and regulation.

The COVID-19 coronavirus is now spreading worldwide. Its pathogen, SARS-CoV-2, has been shown to use angiotensin-converting enzyme 2 (ACE2) as its host cell receptor, same as the severe acute respiratory syndrome coronavirus (SARS-CoV) in 2003. Epidemiology studies found males although only slightly more likely to be infected than females account for the majority of the severely ill and fatality, which also bias for people older than 60 years or with metabolic and cardiovascular diseases.

GTDB: an integrated resource for glycosyltransferase sequences and annotations.

Glycosyltransferases (GTs), a large class of carbohydrate-active enzymes, adds glycosyl moieties to various substrates to generate multiple bioactive compounds, including natural products with pharmaceutical or agrochemical values. Here, we first collected comprehensive information on GTs, including amino acid sequences, coding region sequences, available tertiary structures, protein classification families, catalytic reactions and metabolic pathways. Then, we developed sequence search and molecular docking processes for GTs, resulting in a GTs database (GTDB).

The accelerated aging model reveals critical mechanisms of late-onset Parkinson's disease.

Background: Late-onset Parkinson's disease (LOPD) is a common neurodegenerative disorder and lacks disease-modifying treatments, attracting major attentions as the aggravating trend of aging population. There were numerous evidences supported that accelerated aging was the primary risk factor for LOPD, thus pointed out that the mechanisms of PD should be revealed thoroughly based on aging acceleration. However, how PD was triggered by accelerated aging remained unclear and the systematic prediction model was needed to study the mechanisms of PD.

Cas12a Base Editors Induce Efficient and Specific Editing with Low DNA Damage Response.

The advent of base editors (BEs) holds great potential for correcting pathogenic-related point mutations to treat relevant diseases. However, Cas9 nickase (nCas9)-derived BEs lead to DNA double-strand breaks, which can trigger unwanted DNA damage response (DDR). Here, we show that the original version of catalytically dead Cas12a (dCas12a)-conjugated BEs induce a basal level of DNA breaks and minimally activate DDR proteins, including H2AX, ATM, ATR, and p53.

Rrp6 Regulates Heterochromatic Gene Silencing via ncRNA RUF6 Decay in Malaria Parasites.

The heterochromatin environment plays a central role in silencing genes associated with the malaria parasite's development, survival in the host, and transmission to the mosquito vector. However, the underlying mechanism regulating the dynamic chromatin structure is not understood yet. Here, we have uncovered that Rrp6, an orthologue of eukaryotic RNA exosome-associated RNase, controls the silencing of heterochromatic genes.

Dual base editor catalyzes both cytosine and adenine base conversions in human cells.

Although base editors are useful tools for precise genome editing, current base editors can only convert either adenines or cytosines. We developed a dual adenine and cytosine base editor (A&C-BEmax) by fusing both deaminases with a Cas9 nickase to achieve C-to-T and A-to-G conversions at the same target site. Compared to single base editors, A&C-BEmax's activity on adenines is slightly reduced, whereas activity on cytosines is higher and RNA off-target activity is substantially decreased.

Convergent genomic signatures of high-altitude adaptation among domestic mammals.

Abundant and diverse domestic mammals living on the Tibetan Plateau provide useful materials for investigating adaptive evolution and genetic convergence. Here, we used 327 genomes from horses, sheep, goats, cattle, pigs and dogs living at both high and low altitudes, including 73 genomes generated for this study, to disentangle the genetic mechanisms underlying local adaptation of domestic mammals. Although molecular convergence is comparatively rare at the DNA sequence level, we found convergent signature of positive selection at the gene level, particularly the gene in these Tibetan domestic mammals.

FADB-China: A molecular-level food adulteration database in China based on molecular fingerprints and similarity algorithms prediction expansion.

Food adulteration is a growing concern worldwide. The collation and analysis of food adulteration cases is of immense significance for food safety regulation and research. We collected 961 cases of food adulteration between 1998 and 2019 from the literature reports and announcements released by the Chinese government.

Overexpression of maize transcription factor mEmBP-1 increases photosynthesis, biomass, and yield in rice.

Identifying new options to improve photosynthetic capacity is a major approach to improve crop yield potential. Here we report that overexpression of the gene encoding the transcription factor mEmBP-1 led to simultaneously increased expression of many genes in photosynthesis, including genes encoding Chl a,b-binding proteins (Lhca and Lhcb), PSII (PsbR3 and PsbW) and PSI reaction center subunits (PsaK and PsaN), chloroplast ATP synthase subunit, electron transport reaction components (Fd1 and PC), and also major genes in the Calvin-Benson-Bassham cycle, including those encoding Rubisco, glyceraldehyde phosphate dehydrogenase, fructose bisphosphate aldolase, transketolase, and phosphoribulokinase. These increased expression of photosynthesis genes resulted in increased leaf chlorophyll pigment, photosynthetic rate, biomass growth, and grain yield both in the greenhouse and in the field.

SH3RF3 promotes breast cancer stem-like properties via JNK activation and PTX3 upregulation.

Cancer stem-like cells (CSCs) are the tumorigenic cell subpopulation and contribute to cancer recurrence and metastasis. However, the understanding of CSC regulatory mechanisms remains incomplete. By transcriptomic analysis, we identify a scaffold protein SH3RF3 (also named POSH2) that is upregulated in CSCs of breast cancer clinical tumors and cancer cell lines, and enhances the CSC properties of breast cancer cells.

A rationally engineered cytosine base editor retains high on-target activity while reducing both DNA and RNA off-target effects.

Cytosine base editors (CBEs) offer a powerful tool for correcting point mutations, yet their DNA and RNA off-target activities have caused concerns in biomedical applications. We describe screens of 23 rationally engineered CBE variants, which reveal mutation residues in the predicted DNA-binding site can dramatically decrease the Cas9-independent off-target effects. Furthermore, we obtained a CBE variant-YE1-BE3-FNLS-that retains high on-target editing efficiency while causing extremely low off-target edits and bystander edits.

Single-cell-resolution transcriptome map of human, chimpanzee, bonobo, and macaque brains.

Identification of gene expression traits unique to the human brain sheds light on the molecular mechanisms underlying human evolution. Here, we searched for uniquely human gene expression traits by analyzing 422 brain samples from humans, chimpanzees, bonobos, and macaques representing 33 anatomical regions, as well as 88,047 cell nuclei composing three of these regions. Among 33 regions, cerebral cortex areas, hypothalamus, and cerebellar gray and white matter evolved rapidly in humans.

Dynamic alterations of genome and transcriptome in KRAS G13D mutant CRC PDX model treated with cetuximab.

Background: KRAS mutations have been characterized as the major predictive biomarkers for resistance to cetuximab treatment. However, studies indicate that not all KRAS mutations are associated with equivalent treatment outcomes. KRAS G13D mutations were observed to account for approximately 16% of all KRAS mutations in advanced colorectal cancer patients, and whether these patients can benefit from cetuximab has not been determined.

HPOLabeler: improving prediction of human protein-phenotype associations by learning to rank.

Motivation: Annotating human proteins by abnormal phenotypes has become an important topic. Human Phenotype Ontology (HPO) is a standardized vocabulary of phenotypic abnormalities encountered in human diseases. As of November 2019, only <4000 proteins have been annotated with HPO.

A necroptotic-independent function of MLKL in regulating endothelial cell adhesion molecule expression.

Mixed-lineage kinase domain-like protein (MLKL) is known as the terminal executor of necroptosis. However, its function outside of necroptosis is still not clear. Herein, we demonstrate that MLKL promotes vascular inflammation by regulating the expression of adhesion molecules ICAM1, VCAM1, and E-selectin in endothelial cells (EC).

novoPathFinder: a webserver of designing novel-pathway with integrating GEM-model.

To increase the number of value-added chemicals that can be produced by metabolic engineering and synthetic biology, constructing metabolic space with novel reactions/pathways is crucial. However, with the large number of reactions that existed in the metabolic space and complicated metabolisms within hosts, identifying novel pathways linking two molecules or heterologous pathways when engineering a host to produce a target molecule is an arduous task. Hence, we built a user-friendly web server, novoPathFinder, which has several features: (i) enumerate novel pathways between two specified molecules without considering hosts; (ii) construct heterologous pathways with known or putative reactions for producing target molecule within Escherichia coli or yeast without giving precursor; (iii) estimate novel pathways with considering several categories, including enzyme promiscuity, Synthetic Complex Score (SCScore) and LD50 of intermediates, overall stoichiometric conversions, pathway length, theoretical yields and thermodynamic feasibility.

Probiotics and fructo-oligosaccharide intervention modulate the microbiota-gut brain axis to improve autism spectrum reducing also the hyper-serotonergic state and the dopamine metabolism disorder.

The prevalence of autism spectrum disorders (ASD) is increasing, but its etiology remains elusive and hence an effective treatment is not available. Previous research conducted on animal models suggests that microbiota-gut-brain axis may contribute to ASD pathology and more human research is needed. This study was divided into two stages,.