A large-scale effort, termed the Secreted Protein Discovery Initiative (SPDI), was undertaken to identify novel secreted and transmembrane proteins. In the first of several approaches, a biological ...signal sequence trap in yeast cells was utilized to identify cDNA clones encoding putative secreted proteins. A second strategy utilized various algorithms that recognize features such as the hydrophobic properties of signal sequences to identify putative proteins encoded by expressed sequence tags (ESTs) from human cDNA libraries. A third approach surveyed ESTs for protein sequence similarity to a set of known receptors and their ligands with the BLAST algorithm. Finally, both signal-sequence prediction algorithms and BLAST were used to identify single exons of potential genes from within human genomic sequence. The isolation of full-length cDNA clones for each of these candidate genes resulted in the identification of >1000 novel proteins. A total of 256 of these cDNAs are still novel, including variants and novel genes, per the most recent GenBank release version. The success of this large-scale effort was assessed by a bioinformatics analysis of the proteins through predictions of protein domains, subcellular localizations, and possible functional roles. The SPDI collection should facilitate efforts to better understand intercellular communication, may lead to new understandings of human diseases, and provides potential opportunities for the development of therapeutics.
REF Select, expert system software, has been developed to assist in the selection of optimal restriction endonucleases for restriction endonuclease fingerprinting (REF), a method for rapid and ...sensitive mutation screening of long DNA segments (1-2 kb). The REF method typically involves six separate digestions with up to two restriction endnonucleases used in each digestion. If done manually, performing a comprehensive review of the large number of possible sets of restriction endonucleases that could be used (over 10
in the example presented here) and making an optimal choice is not feasible. Furthermore, the typical nonoptimal manual selection takes approximately 8 h by someone experienced with REF. REF Select enables a comprehensive review of the possible sets and a consistent, objective and fast selection of an optimal set by using a two-step strategy: the selection of sets that meet specific constraints, which is followed by a ranking of those sets by an optimality score. Based on our experience with REF, we chose default selection and ranking parameters to help the user get started quickly. These parameters form a knowledge base that can be customized and then saved by the user. In conclusion, REF Select facilitates the general application of REF by serving as an expert system for the selection of optimal restriction endonucleases. We demonstrated REF Select using an example segment from the human
gene.
Primary Sjögren's syndrome (pSS) is a chronic autoimmune disease that is estimated to affect 35 million people worldwide and is characterized by lymphocytic infiltration, elevated circulating ...autoantibodies, and proinflammatory cytokines. The key immune cell subset changes and the TCR/BCR repertoire alterations in pSS patients remain unclear. In this study, we sought to comprehensively characterize the transcriptional changes in PBMCs of pSS patients by single-cell RNA sequencing and single-cell V(D)J sequencing. Naive CD8
T cells and mucosal-associated invariant T cells were markedly decreased but regulatory T cells were increased in pSS patients. There were a large number of differentially expressed genes shared by multiple subpopulations of T cells and B cells. Abnormal signaling pathways, including Ag processing and presentation, the BCR signaling pathway, the TCR signaling pathway, and Epstein-Barr virus infection, were highly enriched in pSS patients. Moreover, there were obvious differences in the CD30, FLT3, IFN-II, IL-1, IL-2, IL-6, IL-10, RESISTIN, TGF-β, TNF, and VEGF signaling networks between pSS patients and healthy controls. Single-cell TCR and BCR repertoire analysis showed that there was a lower diversity of T cells in pSS patients than in healthy controls; however, there was no significant difference in the degree of clonal expansion, CDR3 length distribution, or degree of sequence sharing. Notably, our results further emphasize the functional importance of αβ pairing in determining Ag specificity. In conclusion, our analysis provides a comprehensive single-cell map of gene expression and TCR/BCR profiles in pSS patients for a better understanding of the pathogenesis, diagnosis, and treatment of pSS.
The Seq2Seq abstract summarization model based on long short-term memory (LSTM) is very effective for short text summarization. However, LSTM is limited by long-term dependencies, which can ...potentially result in salient information loss when long text is processed by the Seq2Seq model based on LSTM. To overcome the long-term dependence limitation, an encoder-decoder model based on the dynamic residual network is proposed in this work. The model can dynamically select an optimal state from the state history to establish a connection with the current state to improve the LSTM long sequence dependencies according to the current decoding environment. Because the dynamic residual connections will result in long-term connection-dependent words, a new method based on reinforcement learning is proposed to simulate the dependence between words, which is then implemented into the training process of the model. This model is verified using the CNN/Daily Mail and New York Times datasets, and the experimental results show that the proposed model achieves significant improvements in capturing long-term dependencies compared with the traditional LSTM-based Seq2Seq abstractive summarization model.
The leakage of the injection–production string is one of the important hidden dangers for the safe and efficient operation of underground salt cavern gas storage. Although distributed fiber optic ...temperature measurement system (DTS) can accurately locate the position of the string leakage port, how to establish the quantitative relationship between the temperature difference and leakage rate of the leakage port still needs further exploration. This paper proposes a new quantitative prediction model based on a DTS for the leakage monitoring of the injection–production string of salt cavern gas storage. The model takes into account the gas’s physical parameters, unstable temperature conditions, and the Joule–Thomson effect. In order to verify the accuracy of the model, a simulation experiment of string leakage based on a DTS was carried out. The test results show that the relative deviation between the predicted leakage rate and the measured value is less than 5% compared with the calculated value. When the leakage rate drops to 0.16 m3/h and the temperature range is less than 0.5 °C, it is difficult to accurately monitor the DTS. The results of this study help to improve the early warning time of underground salt cavern gas storage string leakage.
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•An improved heat transfer model was proposed with an average error of 3.26%.•Heat transfer mechanism and gas Joule-Thomson effect were both considered.•Temperature spatial ...distribution in the cavity and surrounding rock was obtained.•The maximum temperature difference in the salt cavern can reach 14.94 °C.•A 15 m3/s decrease in gas withdrawal rate can increase temperature by 23.41%.
Oversimplification of the heat transfer mechanism and assumption of uniform temperature and pressure in the salt cavern could cause significant errors when modeling temperature fields. This work proposed a coupled transient flow and heat transfer model for gas storage in the underground salt cavern to reflect the thermal behaviors between gas and surrounding rock, particularly the gas Joule-Thomson effect during gas operation. Then, a fully coupled numerical solution method based on a unified matrix is presented. An average error of 3.26% was observed between the model and field data quoted in literature. The case study indicates that during the gas withdrawal period, the maximum temperature difference in the salt cavern can reach 14.94 °C, while the temperature drop of the cavity wall is only about 4.07 °C, which is quite different from the traditional assumption. A special focus was given to the gas withdrawal rate, which seemed to have the most significant influence on the evolution of the temperature field in the salt cavern. Compared with the gas withdrawal rate of 35 m3/s, reducing the gas withdrawal rate to 20 m3/s can increase the minimum temperature by approximately 23.41%. This study could add further insights into the thermal performance during gas operation in the salt cavern and help to reveal the evolution of the temperature field in the cavity and surrounding rock.
Systemic lupus erythematosus (SLE) is a chronic autoimmune disease for which there is no cure. Effective diagnosis and precise assessment of disease exacerbation remains a major challenge.
We ...performed peripheral blood mononuclear cell (PBMC) proteomics of a discovery cohort, including patients with active SLE and inactive SLE, patients with rheumatoid arthritis (RA), and healthy controls (HC). Then, we performed a machine learning pipeline to identify biomarker combinations. The biomarker combinations were further validated using enzyme-linked immunosorbent assays (ELISAs) in another cohort. Single-cell RNA sequencing (scRNA-seq) data from active SLE, inactive SLE, and HC PBMC samples further elucidated the potential immune cellular sources of each of these PBMC biomarkers.
Screening of the PBMC proteome identified 1023, 168, and 124 proteins that were significantly different between SLE vs. HC, SLE vs. RA, and active SLE vs. inactive SLE, respectively. The machine learning pipeline identified two biomarker combinations that accurately distinguished patients with SLE from controls and discriminated between active and inactive SLE. The validated results of ELISAs for two biomarker combinations were in line with the discovery cohort results. Among them, the six-protein combination (IFIT3, MX1, TOMM40, STAT1, STAT2, and OAS3) exhibited good performance for SLE disease diagnosis, with AUC of 0.723 and 0.815 for distinguishing SLE from HC and RA, respectively. Nine-protein combination (PHACTR2, GOT2, L-selectin, CMC4, MAP2K1, CMPK2, ECPAS, SRA1, and STAT2) showed a robust performance in assessing disease exacerbation (AUC=0.990). Further, the potential immune cellular sources of nine PBMC biomarkers, which had the consistent changes with the proteomics data, were elucidated by PBMC scRNAseq.
Unbiased proteomic quantification and experimental validation of PBMC samples from two cohorts of patients with SLE were identified as biomarker combinations for diagnosis and activity monitoring. Furthermore, the immune cell subtype origin of the biomarkers in the transcript expression level was determined using PBMC scRNAseq. These findings present valuable PBMC biomarkers associated with SLE and may reveal potential therapeutic targets.
Detecting severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) needs human samples, which inevitably contain trace human DNA and RNA. Sequence similarity may cause invalid detection results; ...however, there is still a lack of gene similarity analysis of SARS-CoV-2 and humans. All publicly reported complete genome assemblies in the Entrez genome database were collected for multiple sequence alignment, similarity and phylogenetic analysis. The complete genomes showed high similarity (>99.88% sequence identity). Phylogenetic analysis divided these viruses into three major clades with significant geographic group effects. Viruses from the United States showed considerable variability. Sequence similarity analysis revealed that SARS-CoV-2 has 612 similar sequences with the human genome and 100 similar sequences with the human transcriptome. The sequence characteristics and genome distribution of these similar sequences were confirmed. The sequence similarity and evolutionary mutations provide indispensable references for dynamic updates of SARS-CoV-2 detection primers and methods.
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