Mineralogy and Geochemistry of Rare Earth Elements in Carboniferous-Permian Coals at the Eastern Margin of the Ordos Basin.

This article used Carboniferous-Permian coals from the Jungar, Hedong, and Weibei Coalfields in the east of the Ordos Basin as research samples. Characteristics of coal quality, petrology, mineralogy, and geochemistry were analyzed by proximate analysis, inductively coupled plasma mass spectrometry, X-ray fluorescence spectroscopy, X-ray diffraction analysis, scanning electron microscopy-energy spectrum analysis, and incident light microscope. The enrichment regulations, distribution patterns, and occurrences of REY (rare earth element and yttrium) in coal under different geological conditions were compared. Geological significance and the influence of REY were then discussed. The average REY of Permian coal in the eastern margin of the basin is 127.9 µg/g, CC = 1.87, and the average REY of Carboniferous coal is 117.49 µg/g, CC = 1.72, which are within the normal enrichment range. The inorganic affinity of REYs in the study area is strong and mainly occurs in clay minerals and detrital phosphates and correlates well with LREY. The Permian coal sedimentary environment is more oxidized than the Taiyuan formation, and the Carboniferous coal sedimentary environment is noticeably more affected by marine water. With an increasing degree of coalification, the concentration of rare earth elements (REE) in high-rank coal vitrinite is lower than that in inertinite. In contrast, the concentration of REEs in low-rank coal is the opposite. This is because the oxygen-containing functional groups that can combine with REEs in vitrinite reduce significantly, resulting in the loss of trace elements into other forms. The provenance of the northern and central regions of the study area is mainly sedimentary rocks, granite, alkaline basalt, and continental tholeiite, while the southern region is mainly granite and sedimentary rocks.

SEPPA-mAb: spatial epitope prediction of protein antigens for mAbs.

Identifying the exact epitope positions for a monoclonal antibody (mAb) is of critical importance yet highly challenging to the Ab design of biomedical research. Based on previous versions of SEPPA 3.0, we present SEPPA-mAb for the above purpose with high accuracy and low false positive rate (FPR), suitable for both experimental and modelled structures. In practice, SEPPA-mAb appended a fingerprints-based patch model to SEPPA 3.0, considering the structural and physic-chemical complementarity between a possible epitope patch and the complementarity-determining region of mAb and trained on 860 representative antigen-antibody complexes. On independent testing of 193 antigen-antibody pairs, SEPPA-mAb achieved an accuracy of 0.873 with an FPR of 0.097 in classifying epitope and non-epitope residues under the default threshold, while docking-based methods gave the best AUC of 0.691, and the top epitope prediction tool gave AUC of 0.730 with balanced accuracy of 0.635. A study on 36 independent HIV glycoproteins displayed a high accuracy of 0.918 and a low FPR of 0.058. Further testing illustrated outstanding robustness on new antigens and modelled antibodies. Being the first online tool predicting mAb-specific epitopes, SEPPA-mAb may help to discover new epitopes and design better mAbs for therapeutic and diagnostic purposes. SEPPA-mAb can be accessed at http://www.badd-cao.net/seppa-mab/.

MetNC: Predicting Metabolites in vivo for Natural Compounds.

Natural compounds (NCs) undergo complicated biotransformation in vivo to produce diverse forms of metabolites dynamically, many of which are of high medicinal value. Predicting the profiles of chemical products may help to narrow down possible candidates, yet current computational methods for predicting biotransformation largely focus on synthetic compounds. Here, we proposed a method of MetNC, a tailor-made method for NC biotransformation prediction, after exploring the overall patterns of NC in vivo metabolism. Based on 850 pairs of the biotransformation dataset validated by comprehensive in vivo experiments with sourcing compounds from medicinal plants, MetNC was designed to produce a list of potential metabolites through simulating in vivo biotransformation and then prioritize true metabolites into the top list according to the functional groups in compound structures and steric hindrance around the reaction sites. Among the well-known peers of GLORYx and BioTransformer, MetNC gave the highest performance in both the metabolite coverage and the ability to short-list true products. More importantly, MetNC seemed to display an extra advantage in recommending the microbiota-transformed metabolites, suggesting its potential usefulness in the overall metabolism estimation. In summary, complemented to those techniques focusing on synthetic compounds, MetNC may help to fill the gap of natural compound metabolism and narrow down those products likely to be identified in vivo.

HIT 2.0: an enhanced platform for Herbal Ingredients' Targets.

Literature-described targets of herbal ingredients have been explored to facilitate the mechanistic study of herbs, as well as the new drug discovery. Though several databases provided similar information, the majority of them are limited to literatures before 2010 and need to be updated urgently. HIT 2.0 was here constructed as the latest curated dataset focusing on Herbal Ingredients' Targets covering PubMed literatures 2000-2020. Currently, HIT 2.0 hosts 10 031 compound-target activity pairs with quality indicators between 2208 targets and 1237 ingredients from more than 1250 reputable herbs. The molecular targets cover those genes/proteins being directly/indirectly activated/inhibited, protein binders, and enzymes substrates or products. Also included are those genes regulated under the treatment of individual ingredient. Crosslinks were made to databases of TTD, DrugBank, KEGG, PDB, UniProt, Pfam, NCBI, TCM-ID and others. More importantly, HIT enables automatic Target-mining and My-target curation from daily released PubMed literatures. Thus, users can retrieve and download the latest abstracts containing potential targets for interested compounds, even for those not yet covered in HIT. Further, users can log into 'My-target' system, to curate personal target-profiling on line based on retrieved abstracts. HIT can be accessible at http://hit2.badd-cao.net.

SEPPA 3.0-enhanced spatial epitope prediction enabling glycoprotein antigens.

B-cell epitope information is critical to immune therapy and vaccine design. Protein epitopes can be significantly affected by glycosylation, while no methods have considered this till now. Based on previous versions of Spatial Epitope Prediction of Protein Antigens (SEPPA), we here present an enhanced tool SEPPA 3.0, enabling glycoprotein antigens. Parameters were updated based on the latest and largest dataset. Then, additional micro-environmental features of glycosylation triangles and glycosylation-related amino acid indexes were added as important classifiers, coupled with final calibration based on neighboring antigenicity. Logistic regression model was retained as SEPPA 2.0. The AUC value of 0.794 was obtained through 10-fold cross-validation on internal validation. Independent testing on general protein antigens resulted in AUC of 0.740 with BA (balanced accuracy) of 0.657 as baseline of SEPPA 3.0. Most importantly, when tested on independent glycoprotein antigens only, SEPPA 3.0 gave an AUC of 0.749 and BA of 0.665, leading the top performance among peers. As the first server enabling accurate epitope prediction for glycoproteins, SEPPA 3.0 shows significant advantages over popular peers on both general protein and glycoprotein antigens. It can be accessed at http://bidd2.nus.edu.sg/SEPPA3/ or at http://www.badd-cao.net/seppa3/index.html. Batch query is supported.