Elucidation of subfamily segregation and intramolecular coevolution of the olfactomedin-like proteins by comprehensive phylogenetic analysis and gene expression pattern assessment

AbstractThe categorization of genes by structural distinctions relevant to biological characteristics is very important for understanding of gene functions and predicting functional implications of uncharacterized genes. It was absolutely necessary to deploy an effective and efficient strategy to deal with the complexity of the large olfactomedin-like (OLF) gene family sharing sequence similarity but playing diversified roles in many important biological processes, as the simple highest-hit homology analysis gave incomprehensive results and led to inappropriate annotation for some uncharacterized OLF members. In light of evolutionary information that may facilitate the classification of the OLF family and proper association of novel OLF genes with characterized homologs, we performed phylogenetic analysis on all 116 OLF proteins currently available, including two novel members cloned by our group. The OLF family segregated into seven subfamilies and members with similar domain compositions or functional properties all fell into relevant subfamilies. Furthermore, our Northern blot analysis and previous studies revealed that the typical human OLF members in each subfamily exhibited tissue-specific expression patterns, which in turn supported the segregation of the OLF subfamilies with functional divergence. Interestingly, the phylogenetic tree topology for the OLF domains alone was almost identical with that of the full-length tree representing the unique phylogenetic feature of full-length OLF proteins and their particular domain compositions. Moreover, each of the major functional domains of OLF proteins kept the same phylogenetic feature in defining similar topology of the tree. It indicates that the OLF domain and the various domains in flanking non-OLF regions have coevolved and are likely to be functionally interdependent. Expanded by a plausible gene duplication and domain couplings scenario, the OLF family comprises seven evolutionarily and functionally distinct subfamilies, in which each member shares similar structural and functional characteristics including the composition of coevolved and interdependent domains. The phylogenetically classified and preliminarily assessed subfamily framework may greatly facilitate the studying on the OLF proteins. Furthermore, it also demonstrated a feasible and reliable strategy to categorize novel genes and predict the functional implications of uncharacterized proteins based on the comprehensive phylogenetic classification of the subfamilies and their relevance to preliminary functional characteristics

SjTPdb: integrated transcriptome and proteome database and analysis platform for Schistosoma japonicum

<p>Abstract</p> <p>Background</p> <p><it>Schistosoma japonicum </it>is one of the three major blood fluke species, the etiological agents of schistosomiasis which remains a serious public health problem with an estimated 200 million people infected in 76 countries. In recent years, enormous amounts of both transcriptomic and proteomic data of schistosomes have become available, providing information on gene expression profiles for developmental stages and tissues of <it>S. japonicum</it>. Here, we establish a public searchable database, termed SjTPdb, with integrated transcriptomic and proteomic data of <it>S. japonicum</it>, to enable more efficient access and utility of these data and to facilitate the study of schistosome biology, physiology and evolution.</p> <p>Description</p> <p>All the available ESTs, EST clusters, and the proteomic dataset of <it>S. japonicum </it>are deposited in SjTPdb. The core of the database is the 8,420 <it>S. japonicum </it>proteins translated from the EST clusters, which are well annotated for sequence similarity, structural features, functional ontology, genomic variations and expression patterns across developmental stages and tissues including the tegument and eggshell of this flatworm. The data can be queried by simple text search, BLAST search, search based on developmental stage of the life cycle, and an integrated search for more specific information. A PHP-based web interface allows users to browse and query SjTPdb, and moreover to switch to external databases by the following embedded links.</p> <p>Conclusion</p> <p>SjTPdb is the first schistosome database with detailed annotations for schistosome proteins. It is also the first integrated database of both transcriptome and proteome of <it>S. japonicum</it>, providing a comprehensive data resource and research platform to facilitate functional genomics of schistosome. SjTPdb is available from URL: <url>http://function.chgc.sh.cn/sj-proteome/index.htm</url>.</p

Genome-Wide Identification of Schistosoma japonicum MicroRNAs Using a Deep-Sequencing Approach

BACKGROUND: Human schistosomiasis is one of the most prevalent and serious parasitic diseases worldwide. Schistosoma japonicum is one of important pathogens of this disease. MicroRNAs (miRNAs) are a large group of non-coding RNAs that play important roles in regulating gene expression and protein translation in animals. Genome-wide identification of miRNAs in a given organism is a critical step to facilitating our understanding of genome organization, genome biology, evolution, and posttranscriptional regulation. METHODOLOGY/PRINCIPAL FINDINGS: We sequenced two small RNA libraries prepared from different stages of the life cycle of S. japonicum, immature schistosomula and mature pairing adults, through a deep DNA sequencing approach, which yielded approximately 12 million high-quality short sequence reads containing a total of approximately 2 million non-redundant tags. Based on a bioinformatics pipeline, we identified 176 new S. japonicum miRNAs, of which some exhibited a differential pattern of expression between the two stages. Although 21 S. japonicum miRNAs are orthologs of known miRNAs within the metazoans, some nucleotides at many positions of Schistosoma miRNAs, such as miR-8, let-7, miR-10, miR-31, miR-92, miR-124, and miR-125, are indeed significantly distinct from other bilaterian orthologs. In addition, both miR-71 and some miR-2 family members in tandem are found to be clustered in a reversal direction model on two genomic loci, and two pairs of novel S. japonicum miRNAs were derived from sense and antisense DNA strands at the same genomic loci. CONCLUSIONS/SIGNIFICANCE: The collection of S. japonicum miRNAs could be used as a new platform to study the genomic structure, gene regulation and networks, evolutionary processes, development, and host-parasite interactions. Some S. japonicum miRNAs and their clusters could represent the ancestral forms of the conserved orthologues and a model for the genesis of novel miRNAs

A Non-stochastic Optimization Algorithm for Neural-network Quantum States

Neural-network quantum states (NQS) employ artificial neural networks to encode many-body wave functions in second quantization through variational Monte Carlo (VMC). They have recently been applied to accurately describe electronic wave functions of molecules and have shown the challenges in efficiency comparing with traditional quantum chemistry methods. Here we introduce a general non-stochastic optimization algorithm for NQS in chemical systems, which deterministically generates a selected set of important configurations simultaneously with energy evaluation of NQS. This method bypasses the need for Markov-chain Monte Carlo within the VMC framework, thereby accelerating the entire optimization process. Furthermore, this newly-developed non-stochastic optimization algorithm for NQS offers comparable or superior accuracy compared to its stochastic counterpart and ensures more stable convergence. The application of this model to test molecules exhibiting strong electron correlations provides further insight into the performance of NQS in chemical systems and opens avenues for future enhancements.Comment: 30 pages, 7 figures, and 1 tabl

Case Report: Durable complete response of metastatic hepatocellular carcinoma with asymptomatic hyperamylasemia to combined immunotherapy of anti-cytotoxic T lymphocyte-associated antigen 4 plus anti-programmed cell death-1 antibodies

BackgroundCombined immunotherapy has shown promising results in the treatment of advanced HCC, whereas the priority population that would respond to the combined immunotherapy is still elusive. In addition, HCC with asymptomatic hyperamylasemia was not reported previously.Case presentationAn aged patient was diagnosed as HCC with BCLC stage C (bone metastasis). Notably, this patient showed asymptomatic hyperamylasemia. The patient was then enrolled in a trial evaluating combined immunotherapy of anti-PD-1 antibody sintilimab (IBI308) plus anti-CTLA-4 antibody (IBI310) in advanced HCC. After being treated with combined immunotherapy, this patient rapidly achieved complete response (CR) according to mRECIST criteria or immune partial response (iPR) according to iRECIST criteria and maintain the CR state for more than 12 months. Interestingly, serum levels of amylase and lipase in this patient were reduced after treatment.ConclusionWe reported, for the first time, a case of metastatic HCC with asymptomatic hyperamylasemia, and suggested that HCC patients with asymptomatic hyperamylasemia may benefit from combined immunotherapy of anti-CTLA-4 and PD-1 antibodies

Fully passive Measurement Device Independent Quantum Key Distribution

Measurement-device-independent quantum key distribution (MDI-QKD) can resist all attacks on the detection devices, but there are still some security issues related to the source side. One possible solution is to use the passive protocol to eliminate the side channels introduced by active modulators at the source. Recently, a fully passive QKD protocol has been proposed that can simultaneously achieve passive encoding and passive decoy-state modulation using linear optics. In this work, we propose a fully passive MDI-QKD scheme that can protect the system from both side channels of source modulators and attacks on the measurement devices, which can significantly improve the implementation security of the QKD systems. We provide a specific passive encoding strategy and a method for decoy-state analysis, followed by simulation results for the secure key rate in the asymptotic scenario. Our work offers a feasible way to improve the implementation security of QKD systems, and serves as a reference for achieving passive QKD schemes using realistic devices

Unbalanced-basis-misalignment tolerant measurement-device-independent quantum key distribution

Measurement-device-independent quantum key distribution (MDIQKD) is a revolutionary protocol since it is physically immune to all attacks on the detection side. However, the protocol still keeps the strict assumptions on the source side that the four BB84-states must be perfectly prepared to ensure security. Some protocols release part of the assumptions in the encoding system to keep the practical security, but the performance would be dramatically reduced. In this work, we present a MDIQKD protocol that requires less knowledge of encoding system to combat the troublesome modulation errors and fluctuations. We have also experimentally demonstrated the protocol. The result indicates the high-performance and good security for its practical applications. Besides, its robustness and flexibility exhibit a good value for complex scenarios such as the QKD networks.Comment: 22 pages, 9 figure