ProTG4: A Web Server to Approximate the Sequence of a Generic Protein From an in Silico Library of Translatable G-Quadruplex (TG4)-Mapped Peptides

An RNA G-quadruplex in the protein coding segment of mRNA is translatable [Formula: see text] and may potentially impact protein translation. This can be consequent to staggered ribosomal synthesis and/or result in an increased frequency of missense translational events. A mathematical model of the peptides that encompass the substituted amino acids, ie, the [Formula: see text]-mapped peptidome, has been previously studied. However, the significance and relevance to disease biology of this model remains to be established. ProTG4 computes a confidence-of-sequence-identity [Formula: see text]-score, which is the average weighted length of every matched [Formula: see text]-mapped peptide in a generic protein sequence. The weighted length is the product of the length of the peptide and the probability of its non-random occurrence in a library of randomly generated sequences of equivalent lengths. This is then averaged over the entire length of the protein sequence. ProTG4 is simple to operate, has clear instructions, and is accompanied by a set of ready-to-use examples. The rationale of the study, algorithms deployed, and the computational pipeline deployed are also part of the web page. Analyses by ProTG4 of taxonomically diverse protein sequences suggest that there is significant homology to [Formula: see text]-mapped peptides. These findings, especially in potentially infectious and infesting agents, offer plausible explanations into the aetiology and pathogenesis of certain proteopathies. ProTG4 can also provide a quantitative measure to identify and annotate the canonical form of a generic protein sequence from its known isoforms. The article presents several case studies and discusses the relevance of ProTG4-assisted peptide analysis in gaining insights into various mechanisms of disease biology (mistranslation, alternate splicing, amino acid substitutions).

Artificial intelligence predicts the immunogenic landscape of SARS-CoV-2: toward universal blueprints for vaccine designs

This protocol predicts blueprints for vaccine design that contain a broad repertoire of T-cell epitopes optimized for the global population. The protocol first requires a screening of the SARS-CoV-2 proteome using immunogenicity predictors to generate comprehensive epitope maps. Then, these epitope maps are used as input to Monte Carlo simulations designed to identify statistically significant “epitope hotspot” regions in the virus that are most likely to be immunogenic. The epitope hotspots that share significant homology with proteins in the human proteome are removed to reduce the chance of inducing off-target autoimmune responses. Finally, a database of the actual HLA genotypes of citizens is used to develop a “digital twin” type simulation to model how effective different combinations of hotspots would work in a diverse human population. The approach identifies an optimal constellation of epitope hotspots that could provide maximum coverage in the human population.

Epitope profiling reveals binding signatures of SARS-CoV-2 immune response and cross-reactivity with endemic HCoVs

A major goal of current SARS-CoV-2 vaccine efforts is to elicit antibody responses that confer protection. Mapping the epitope targets of the SARS-CoV-2 antibody response is critical for innovative vaccine design, diagnostics, and development of therapeutics. Here, we developed a phage display library to map antibody binding sites at high resolution within the complete viral proteomes of all human-infecting coronaviruses in patients with mild or moderate/severe COVID-19. The dominant immune responses to SARS-CoV-2 were targeted to regions spanning the Spike protein, Nucleocapsid, and ORF1ab. Some epitopes were identified in the majority of samples while others were rare, and we found variation in the number of epitopes targeted by different individuals. We also identified a set of cross-reactive sequences that were bound by antibodies in SARS-CoV-2 unexposed individuals. Finally, we uncovered a subset of enriched epitopes from commonly circulating human coronaviruses with significant homology to highly reactive SARS-CoV-2 sequences.

MAGE-C2/CT10 promotes growth and metastasis through upregulating c-Myc expression in prostate cancer

Prostate cancer (PC) is the most common reproductive cancer in men and the third leading cause of cancer death among men worldwide. Recently targeted therapy showed a significant therapeutic effect on PC, whereas finding more PC therapeutic target is still urgently needed. Melanoma-associated antigen-encoding C2 (MAGE-C2/CT10), which have significant homology with the MAGE-C1/CT-7 gene, was known to be involved in the development of a variety of tumors. However, the role and mechanism of MAGE-C2/CT10 in prostate cancer remains unclear. Herein, we found the high levels of MAGE-C2/CT10 in highly metastatic prostate cancer. Our findings confirmed that the depletion of MAGE-C2/CT10 suppressed the growth of PC cells, and restrained PC cell migration and invasion in vitro. We noticed MAGE-C2/CT10 could stimulate c-Myc expression via FBP1, and further contributed to PC cell proliferation and motility. Performing in vivo assays, we demonstrated MAGE-C2/CT10 promoted tumor growth and metastasis of PC cells in mice. Collectively, we found the abnormal expression of MAGE-C2/CT10 in PC, and revealed the regulatory mechanism underlying MAGE-C2/CT10 promoting PC progression and metastasis.

Zygnema circumcarinatum UTEX 1559 chloroplast and mitochondrial genomes provide insight into land plant evolution

The complete chloroplast and mitochondrial genomes of Charophyta have shed new light on land plant terrestrialization. Here, we report the organellar genomes of the Zygnema circumcarinatum strain UTEX 1559, and a comparative genomics investigation of 33 plastomes and 18 mitogenomes of Chlorophyta, Charophyta (including UTEX 1559 and its conspecific relative SAG 698-1a), and Embryophyta. Gene presence/absence was determined across these plastomes and mitogenomes. A comparison between the plastomes of UTEX 1559 (157 548 bp) and SAG 698-1a (165 372 bp) revealed very similar gene contents, but substantial genome rearrangements. Surprisingly, the two plastomes share only 85.69% nucleotide sequence identity. The UTEX 1559 mitogenome size is 215 954 bp, the largest among all sequenced Charophyta. Interestingly, this large mitogenome contains a 50 kb region without homology to any other organellar genomes, which is flanked by two 86 bp direct repeats and contains 15 ORFs. These ORFs have significant homology to proteins from bacteria and plants with functions such as primase, RNA polymerase, and DNA polymerase. We conclude that (i) the previously published SAG 698-1a plastome is probably from a different Zygnema species, and (ii) the 50 kb region in the UTEX 1559 mitogenome might be recently acquired as a mobile element.

The US CDC RT-PCR probes for the Wuhan 2019-nCoV are non-specific for SARS - there is a better non-specific 500bp option (21852-22427) within the spike-protein

The World Health Organization has declared the Wuhan coronavirus [1–3] outbreak a public health emer- gency on 30th Jan, 2020. An accurate detection of the Wuhan virus is imperative to avoid false positives, since 2019-nCoV [2,3] shares significant homology [4] with other species.On the 24th of Jan, the CDC has published a list of 3 probes (Fig 1) for detecting the 2019-nCoV. Detection of all three probes would give a positive result, while detection of one or two gives an ’inconclusive result’ (and obviously negative when none are found).All 3 probes will have significant homology in other strains (Table 1 and Fig 2 ) - specifically SARS (Severe Acute Respiratory Syndrome). A much more specific option is to look within a 500bp genomic fragment in the N-terminal of the spike protein (Accid:NC 045512.2 [2],21852-22427, SI.cdc:nCoVFULLSLICE.fa), which seems to the most perturbed in this virulent strain [5].It is also important to have a common repository for all countries to be following a similar protocol. Many papers do no provide what PCR was used to detect coronaviruses [6].

Comparative studies of Aspergillus fumigatus 2-methylcitrate synthase and human citrate synthase

Aspergillus fumigatus is a ubiquitous fungus that is not only a problem in agriculture, but also in healthcare. Aspergillus fumigatus drug resistance is becoming more prominent which is mainly attributed to the widespread use of fungicides in agriculture. The fungi-specific 2-methylcitrate cycle is responsible for detoxifying propionyl-CoA, a toxic metabolite produced as the fungus breaks down proteins and amino acids. The enzyme responsible for this detoxification is 2-methylcitrate synthase (mcsA) and is a potential candidate for the design of new anti-fungals. However, mcsA is very similar in structure to human citrate synthase (hCS) and catalyzes the same reaction. Therefore, both enzymes were studied in parallel to provide foundations for design of mcsA-specific inhibitors. The first crystal structures of citrate synthase from humans and 2-methylcitrate synthase from A. fumigatus are reported. The determined structures capture various conformational states of the enzymes and several inhibitors were identified and characterized. Despite a significant homology, mcsA and hCS display pronounced differences in substrate specificity and cooperativity. Considering that the active sites of the enzymes are almost identical, the differences in reactions catalyzed by enzymes are caused by residues that are in the vicinity of the active site and influence conformational changes of the enzymes.

Nosocomial spread of OXA-232-producing Klebsiella pneumoniae ST15 in a teaching hospital, Shanghai, China

Background The spread and outbreak of Enterobacteriaceae producing OXA-48-like carbapenemases have become more and more prevalent in China. Results A total of 62 non-duplicated OXA-232-producing K. pneumoniae (OXA232Kp) were isolated between 2015 and 2017. An outbreak of OXA232Kp was observed in burn ICU. The 62 OXA232Kp isolates were all belongs to ST15 and categorized into two PFGE types (A and B). Type A was dominated of the isolates, which contained 61 clinical isolates and divided into 10 subtypes (A1-A10). In addition, most of OXA232Kp strains exhibited low-level carbapenems resistance. All strains carried a 6141 bp ColKP3 plasmid harboring the blaOXA-232 gene which is highly homologous to other blaOXA-232-bearing plasmids involved in other studies in eastern China. Conclusions In this study, clone transmission of OXA232Kp ST15was observed. Highly significant homology among the blaOXA-232-bearing plasmids indicated the important role of the 6.1 kb ColE-like plasmid on the prevalence of blaOXA-232 gene in China.

Complete genome sequence of new virulent actinophages belonging to Streptomyces flavovirens

Complete genome sequence of new virulent actinophages belonging to Streptomyces flavovirens We report biological and physiochemical features and use NGS to provide the complete annotated genomes for two new strains (Sf1 and Sf3) of the virulent phage Streptomyces flavovirens, isolated from Egyptian soil samples. The S. flavovirens phages (Sf1 and Sf3) show high adsorption rates (82 and 85 %, respectively), indicating a strong specificity to their host, and their burst sizes were 1.95 and 2.49 virions per mL. The phage genomes are parts of a singleton cluster with sizes of 43,150 bp and 60,934 bp, respectively. the assignment of possible functions to 19 and 28 putative ORFs were identified, which included phage structural proteins, lysis components and metabolic proteins. Comparative genomic analysis revealed significant homology between the two phages and the closest Streptomyces phage (VWB phages). However, the phylogenetic analysis highlighted that the isolated phages belong to the BG Streptomyces phage group but are clearly separated, representing a novel sub-cluster.