Experimental Evaluation of Working Fluid Damage to Gas Transport in a High-Rank Coalbed Methane Reservoir in the Qinshui Basin, China.

Formation damage induced by the injected working fluid runs through the whole life cycle of coalbed methane (CBM) extraction and ultimately reduces the production of CBM wells. The conventional method uses permeability as a parameter to evaluate the formation damage severity to coal by working fluids containing solids. However, less attention has been attracted to the formation damage of the pure liquid phase of the working fluid on the multiscale gas transport process of CBM. Therefore, we present a multiscale working fluid filtrate damage evaluation method considering the desorption, diffusion, and seepage and use it to evaluate high-rank coal in the Qinshui Basin of China. The results show that pure liquids with different pH values and salinities significantly damage the desorption-diffusion and seepage ability of CBM. The damage rates of alkaline fluid, hydrochloric acid fluid, and clear water on the methane desorption capacity of coal are 63.64, 17.63, and 24.34%, respectively, while those on the permeability of coal are 29.88, 42.38, and 46.66%, respectively. The formation damage severity in the seepage process is higher than that in the desorption-diffusion process, which proves the necessity of multiscale working fluid damage evaluation on CBM. Effective channel reduction and resistance increase in gas transport are the mechanisms of working fluid filtrate-induced formation damage, which are caused by water blocking, sensitive mineral swelling and clogging, and strengthened stress sensitivity. In addition to controlling the solid damage of the working fluid, reducing the invasion of the working fluid filtrate and maintaining its compatibility with the coal and formation fluids are even more important to protect the coal reservoir.

An integrated platform for Brucella with knowledge graph technology: From genomic analysis to epidemiological projection.

Motivation: Brucella, the causative agent of brucellosis, is a global zoonotic pathogen that threatens both veterinary and human health. The main sources of brucellosis are farm animals. Importantly, the bacteria can be used for biological warfare purposes, requiring source tracking and routine surveillance in an integrated manner. Additionally, brucellosis is classified among group B infectious diseases in China and has been reported in 31 Chinese provinces to varying degrees in urban areas. From a national biosecurity perspective, research on brucellosis surveillance has garnered considerable attention and requires an integrated platform to provide researchers with easy access to genomic analysis and provide policymakers with an improved understanding of both reported patients and detected cases for the purpose of precision public health interventions. Results: For the first time in China, we have developed a comprehensive information platform for Brucella based on dynamic visualization of the incidence (reported patients) and prevalence (detected cases) of brucellosis in mainland China. Especially, our study establishes a knowledge graph for the literature sources of Brucella data so that it can be expanded, queried, and analyzed. When similar "epidemiological comprehensive platforms" are established in the distant future, we can use knowledge graph to share its information. Additionally, we propose a software package for genomic sequence analysis. This platform provides a specialized, dynamic, and visual point-and-click interface for studying brucellosis in mainland China and improving the exploration of Brucella in the fields of bioinformatics and disease prevention for both human and veterinary medicine.

A Computer Simulation of SARS-CoV-2 Mutation Spectra for Empirical Data Characterization and Analysis.

It is very important to compute the mutation spectra, and simulate the intra-host mutation processes by sequencing data, which is not only for the understanding of SARS-CoV-2 genetic mechanism, but also for epidemic prediction, vaccine, and drug design. However, the current intra-host mutation analysis algorithms are not only inaccurate, but also the simulation methods are unable to quickly and precisely predict new SARS-CoV-2 variants generated from the accumulation of mutations. Therefore, this study proposes a novel accurate strand-specific SARS-CoV-2 intra-host mutation spectra computation method, develops an efficient and fast SARS-CoV-2 intra-host mutation simulation method based on mutation spectra, and establishes an online analysis and visualization platform. Our main results include: (1) There is a significant variability in the SARS-CoV-2 intra-host mutation spectra across different lineages, with the major mutations from G- > A, G- > C, G- > U on the positive-sense strand and C- > U, C- > G, C- > A on the negative-sense strand; (2) our mutation simulation reveals the simulation sequence starts to deviate from the base content percentage of Alpha-CoV/Delta-CoV after approximately 620 mutation steps; (3) 2019-NCSS provides an easy-to-use and visualized online platform for SARS-Cov-2 online analysis and mutation simulation.

Nanopore Sequencing Accurately Identifies the Cisplatin Adduct on DNA.

Cisplatin, which selectively binds to N7 atoms of purines to inhibit normal replication and transcription, is a widely applied chemotherapeutic drug in the treatment of cancer. Though direct identification of cisplatin lesions on DNA is of great significance, existing sequencing methods have issues such as complications of preamplification or enrichment-induced false-positive reports. Direct identification of cisplatin lesions by nanopore sequencing (NPS) is in principle feasible. However, relevant investigations have never been reported. By constructing model sequences (83 nucleotides in length) containing a sole cisplatin lesion, identification of corresponding lesions by NPS is achieved with <10 ng of input sequencing library. Moreover, characteristic high-frequency noises caused by cisplatin lesions are consistently observed during NPS, clearly identifiable in corresponding high-pass filtered traces. This feature is, however, never observed in any other combinations of natural DNA bases and could be taken as a reference to identify cisplatin lesions on DNA. Further investigations demonstrate that cisplatin stalls the replication of phi29 DNA polymerase, which appears as a ∼5 pA level fluctuation in the single-molecule resolution. These results have confirmed the feasibility of NPS to identify cisplatin lesions at the genomic level and may provide new insights into understanding the molecular mechanism of platinum-based drugs.

Single Molecule Ratcheting Motion of Peptides in a Mycobacterium smegmatis Porin A (MspA) Nanopore.

Diverse functions of proteins, including synthesis, catalysis, and signaling, result from their highly variable amino acid sequences. The technology allowing for direct analysis of protein sequences, however, is still unsatisfactory. Recent developments of nanopore sequencing of DNA or RNA have motivated attempts to realize nanopore sequencing of peptides in a similar manner. The core challenge has been to achieve a controlled ratcheting motion of the target peptide, which is currently restricted to a limited choice of compatible enzymes. By constructing peptide-oligonucleotide conjugates (POCs) and measurements with nanopore-induced phase-shift sequencing (NIPSS), direct observation of the ratcheting motion of peptides has been successfully achieved. The generated events show a clear sequence dependence on the peptide that is being tested. The method is compatible with peptides with either a conjugated N- or C-terminus. The demonstrated results suggest a proof of concept of nanopore sequencing of peptide and can be useful for peptide fingerprinting.