Understanding the unimodal distributions of cancer occurrence rates: it takes two factors for a cancer to occur.

Data from the SEER reports reveal that the occurrence rate of a cancer type generally follows a unimodal distribution over age, peaking at an age that is cancer-type specific and ranges from 30+ through 70+. Previous studies attribute such bell-shaped distributions to the reduced proliferative potential in senior years but fail to explain why some cancers have their occurrence peak at 30+ or 40+. We present a computational model to offer a new explanation to such distributions. The model uses two factors to explain the observed age-dependent cancer occurrence rates: cancer risk of an organ and the availability level of the growth signals in circulation needed by a cancer type, with the former increasing and the latter decreasing with age. Regression analyses were conducted of known occurrence rates against such factors for triple negative breast cancer, testicular cancer and cervical cancer; and all achieved highly tight fitting results, which were also consistent with clinical, gene-expression and cancer-drug data. These reveal a fundamentally important relationship: while cancer is driven by endogenous stressors, it requires sufficient levels of exogenous growth signals to happen, hence suggesting the realistic possibility for treating cancer via cleaning out the growth signals in circulation needed by a cancer.

Prediction of lncRNA-disease association based on a Laplace normalized random walk with restart algorithm on heterogeneous networks.

BACKGROUND: More and more evidence showed that long non-coding RNAs (lncRNAs) play important roles in the development and progression of human sophisticated diseases. Therefore, predicting human lncRNA-disease associations is a challenging and urgently task in bioinformatics to research of human sophisticated diseases. RESULTS: In the work, a global network-based computational framework called as LRWRHLDA were proposed which is a universal network-based method. Firstly, four isomorphic networks include lncRNA similarity network, disease similarity network, gene similarity network and miRNA similarity network were constructed. And then, six heterogeneous networks include known lncRNA-disease, lncRNA-gene, lncRNA-miRNA, disease-gene, disease-miRNA, and gene-miRNA associations network were applied to design a multi-layer network. Finally, the Laplace normalized random walk with restart algorithm in this global network is suggested to predict the relationship between lncRNAs and diseases. CONCLUSIONS: The ten-fold cross validation is used to evaluate the performance of LRWRHLDA. As a result, LRWRHLDA achieves an AUC of 0.98402, which is higher than other compared methods. Furthermore, LRWRHLDA can predict isolated disease-related lnRNA (isolated lnRNA related disease). The results for colorectal cancer, lung adenocarcinoma, stomach cancer and breast cancer have been verified by other researches. The case studies indicated that our method is effective.

A time series representation of protein sequences for similarity comparison.

Based on the physicochemical indexes of 20 amino acids and the Hungarian algorithm, each amino acid was mapped into a vector. And, the protein sequence can be represented as time series in eleven-dimensional space. In addition, the DTW algorithm was applied to calculate the distance between two time series to compare the similarities of protein sequences. The validity and accuracy of this method was illustrated by similarity comparison of ND5 proteins of nine species. Furthermore, homology analysis of eleven ACE2 proteins, which included human, Malayan pangolin and six species of bats, confirmed that the human had shorter evolutionary distance from the pangolin than those bats. The phylogenetic tree of spike protein sequences of 36 coronaviruses, which were divided into five groups, Class I, Class II, Class III, SARS-CoVs and COVID-19, was constructed.

Theoretical study of polarization dependence of carrier-induced refractive index change of quantum dot.

The influences of dot material component, barrier material component, aspect ratio and carrier density on the refractive index changes of TE mode and TM mode of columnar quantum dot are analyzed, and a multiparameter adjustment method is proposed to realize low polarization dependence of refractive index change. Then the quantum dots with low polarization dependence of refractive index change (<1.5%) within C-band (1530 nm - 1565 nm) are designed, and it shows that quantum dots with different material parameters are anticipated to have similar characteristics of low polarization dependence.

Depth perception based 3D holograms enabled with polarization-independent metasurfaces.

Metasurfaces consist of dielectric nanobrick arrays with different dimensions in the long and short axes can be used to generate different phase delays, predicting a new way to manipulate an incident beam in the two orthogonal directions separately. Here we demonstrate the concept of depth perception based three-dimensional (3D) holograms with polarization-independent metasurfaces. 4-step dielectric metasurfaces-based fan-out optical elements and holograms operating at 658 nm were designed and simulated. Two different holographic images with high fidelity were generated at the same plane in the far field for different polarization states. One can observe the 3D effect of target objects with polarized glasses. With the advantages of ultracompactness, flexibility and replicability, the polarization-independent metasurfaces open up depth perception based stereoscopic imaging in a holographic way.

Dual field-of-view step-zoom metalens.

A conventional optical zoom system is bulky, expensive, and complicated for real-time adjustment. Recent progress in metasurface research has provided a new solution to achieve innovative compact optical systems. In this Letter, we propose a highly integrated step-zoom lens with dual field of view (FOV) based on double-sided metasurfaces. With silicon nanobrick arrays of spatially varying orientations sitting on both sides of a transparent substrate, this ultrathin step-zoom metalens can be designed to focus an incident circular polarized beam with handedness-dependent FOVs without varying the focal plane, which is important for practical applications. The proposed dual FOV step-zoom metalens, with advantages such as ultracompactness, flexibility, and replicability, can find applications in fields that require ultracompact zoom imaging and beam focusing.

Ultracompact high-efficiency polarising beam splitter based on silicon nanobrick arrays.

Since the transmission of anisotropic nano-structures is sensitive to the polarisation of an incident beam, a novel polarising beam splitter (PBS) based on silicon nanobrick arrays is proposed. With careful design of such structures, an incident beam with polarisation direction aligned with the long axis of the nanobrick is almost totally reflected (~98.5%), whilst that along the short axis is nearly totally transmitted (~94.3%). More importantly, by simply changing the width of the nanobrick we can shift the peak response wavelength from 1460 nm to 1625 nm, covering S, C and L bands of the fiber telecommunications windows. The silicon nanobrick-based PBS can find applications in many fields which require ultracompactness, high efficiency, and compatibility with semiconductor industry technologies.

All-silicon nanorod-based Dammann gratings.

Established diffractive optical elements (DOEs), such as Dammann gratings, whose phase profile is controlled by etching different depths into a transparent dielectric substrate, suffer from a contradiction between the complexity of fabrication procedures and the performance of such gratings. In this Letter, we combine the concept of geometric phase and phase modulation in depth, and prove by theoretical analysis and numerical simulation that nanorod arrays etched on a silicon substrate have a characteristic of strong polarization conversion between two circularly polarized states and can act as a highly efficient half-wave plate. More importantly, only by changing the orientation angles of each nanorod can the arrays control the phase of a circularly polarized light, cell by cell. With the above principle, we report the realization of nanorod-based Dammann gratings reaching diffraction efficiencies of 50%-52% in the C-band fiber telecommunications window (1530-1565 nm). In this design, uniform 4×4 spot arrays with an extending angle of 59°×59° can be obtained in the far field. Because of these advantages of the single-step fabrication procedure, accurate phase controlling, and strong polarization conversion, nanorod-based Dammann gratings could be utilized for various practical applications in a range of fields.

Prediction of success for polymerase chain reactions using the Markov maximal order model and support vector machine.

Polymerase chain reaction (PCR) is hailed as one of the monumental scientific techniques of the twentieth century, and has become a common and often indispensable technique in many areas. However, researchers still frequently find some DNA templates very hard to amplify with PCR, although many kinds of endeavors were introduced to optimize the amplification. In fact, during the past decades, the experimental procedure of PCR was always the focus of attention, while the analysis of a DNA template, the PCR experimental subject itself, was almost neglected. Up to now, nobody can certainly identify whether a fragment of DNA can be simply amplified using conventional Taq DNA polymerase-based PCR protocol. Characterizing a DNA template and then developing a reliable and efficient method to predict the success of PCR reactions is thus urgently needed. In this study, by means of the Markov maximal order model, we construct a 48-D feature vector to represent a DNA template. Support vector machine (SVM) is then employed to help evaluate PCR result. To examine the anticipated success rates of our predictor, jackknife cross-validation test is adopted. The overall accuracy of our approach arrives at 93.12%, with the sensitivity, specificity, and MCC of 94.68%, 91.58%, and 0.863%, respectively.

Theoretical study of polarization insensitivity of carrier-induced refractive index change of multiple quantum well.

Characteristics of polarization insensitivity of carrier-induced refractive index change of 1.55 µm tensile-strained multiple quantum well (MQW) are theoretically investigated. A comprehensive MQW model is proposed to effectively extend the application range of previous models. The model considers the temperature variation as well as the nonuniform distribution of injected carrier in MQW. Tensile-strained MQW is expected to achieve polarization insensitivity of carrier-induced refractive index change over a wide wavelength range as temperature varies from 0°C to 40°C, while the magnitude of refractive index change keeps a large value (more than 3 × 10-3). And that the polarization insensitivity of refractive index change can maintain for a wide range of carrier concentration. Multiple quantum well with different material and structure parameters is anticipated to have the similar polarization insensitivity of refractive index change, which shows the design flexibility.

A novel descriptor of protein sequences and its application.

In this paper, a dynamic 3-D graphical representation of protein sequences is introduced based on three physical-chemical properties of amino acids. The coordinates of the graph have direct biological significance, which could reflect the innate structure of the proteins. The information of principal moments of inertia and range of axis coordinate are extracted as a novel mixed descriptor and proposed for the comparison of protein primary sequences. Meanwhile, the Euclidean distance of the normalized descriptor vectors which avoid the influence of the difference in length of protein sequences under consideration is employed as a quantitative measurement of the similarity of proteins. Finally, we take the nine ND5 (NADH dehydrogenase subunit 5) proteins for example and illustrate the effectiveness of our approach.

Single-cell RNA-seq reveals the metabolic status of immune cells response to immunotherapy in triple-negative breast cancer.

Immune checkpoint blockade (ICB) therapy offers promise in the treatment of triple-negative breast cancer (TNBC); however, its limited efficacy in certain TNBC patients poses a challenge. In this study, we elucidated the metabolic mechanism at 'sub-subtype' resolution underlying the non-response to ICB therapy in TNBC. Here, an analytic pipeline was developed to reveal the metabolic heterogeneity, which is correlated with the ICB outcomes, within each immune cell subtype. First, we identified metabolic 'sub-subtypes' within certain cell subtypes, predominantly T cell subsets, which are enriched in ICB non-responders and named as non-responder-enriched (NR-E) clusters. Notably, most of NR-E T metabolic cells exhibit globally higher metabolic activities compared to other cells within the same individual subtype. Further, we investigated the extra-cellular signals that trigger the metabolic status of NR-E T cells. In detail, the prediction of cell-to-cell communication indicated that NR-E T cells are regulated by plasmatic dendritic cells (pDCs) through TNFSF9, as well as by macrophages expressing SIGLEC9. In addition, we also validate the communication between TNFSF9+ pDCs and NR-E T cells utilizing deconvolution of spatial transcriptomics analysis. In summary, our research identified specific metabolic 'sub-subtypes' associated with ICB non-response and uncovered the mechanisms of their regulation in TNBC. And the proposed analytical pipeline can be used to examine metabolic heterogeneity within cell types that correlate with diverse phenotypes.

A 3D graphical representation of protein sequences based on the Gray code.

Based on the order of 6-bit binary Gray code, a cyclic order of 20 amino acids is introduced. A novel 3D graphical representation of protein sequences is proposed according to the CGR of DNA sequences. Furthermore, the mathematical descriptor is suggested to characterize the graphical representation curve. The efficiency of our approach can be illustrated by performing the comparison of similarities/dissimilarities among sequences of the ND5 proteins of nine different species. With the correlation and significance analysis, the comparisons of both our results and results of other graphical representation with the ClustalW's results can show the utility of our approach.

A Generalized Iterative Map for Analysis of Protein Sequences.

AIM AND OBJECTIVE: The similarities comparison of biological sequences is an important task in bioinformatics. The methods of the similarities comparison for biological sequences are divided into two classes: sequence alignment method and alignment-free method. The graphical representation of biological sequences is a kind of alignment-free method, which constitutes a tool for analyzing and visualizing the biological sequences. In this article, a generalized iterative map of protein sequences was suggested to analyze the similarities of biological sequences. MATERIALS AND METHODS: Based on the normalized physicochemical indexes of 20 amino acids, each amino acid can be mapped into a point in 5D space. A generalized iterative function system was introduced to outline a generalized iterative map of protein sequences, which can not only reflect various physicochemical properties of amino acids but also incorporate with different compression ratios of the component of a generalized iterative map. Several properties were proved to illustrate the advantage of the generalized iterative map. The mathematical description of the generalized iterative map was suggested to compare the similarities and dissimilarities of protein sequences. Based on this method, similarities/dissimilarities were compared among ND5 protein sequences, as well as ND6 protein sequences of ten different species. RESULTS: By correlation analysis, the ClustalW results were compared with our similarity/dissimilarity results and other graphical representation results to show the utility of our approach. The comparison results show that our approach has better correlations with ClustalW for all species than other approaches and illustrate the effectiveness of our approach. CONCLUSION: Two examples show that our method not only has good performances and effects in the similarity/dissimilarity analysis of protein sequences but also does not require complex computation.

The graphical representation of protein sequences based on the physicochemical properties and its applications.

Based on the chaos game representation, a 2D graphical representation of protein sequences was introduced in which the 20 amino acids are rearranged in a cyclic order according to their physicochemical properties. The Euclidean distances between the corresponding amino acids from the 2-D graphical representations are computed to find matching (or conserved) fragments of amino acids between the two proteins. Again, the cumulative distance of the 2D-graphical representations is defined to compare the similarity of protein. And, the examination of the similarity among sequences of the ND5 proteins of nine species shows the utility of our approach.

Similarity/dissimilarity studies of protein sequences based on a new 2D graphical representation.

A (two-dimensional) 2D graphical representation of protein sequences based on six physicochemical properties of amino acids is outlined. The numerical characterization of protein graphs is given as descriptors of protein sequences. It is not only useful for comparative study of proteins but also for encoding innate information about the structure of proteins. The coefficient of determination is proposed as a new similarity/dissimilarity measure. Finally, a simple example is taken to highlight the behavior of the new similarity/dissimilarity measure on protein sequences taken from the ND6 (NADH dehydrogenase subunit 6) proteins for eight different species. The results demonstrate the approach is convenient, fast, and efficient.

Analysis of similarity/dissimilarity of protein sequences.

On the basis of a selected pair of physicochemical properties of amino acids, we introduce a dynamic 2D graphical representation of protein sequences. Then, we introduce and compare two numerical characterizations of protein graphs as descriptors to analyze the nine ND5 proteins. The approach is simple, convenient, and fast.

Identification and characteristics of microRNAs from Bombyx mori.

BACKGROUND: MicroRNAs (miRNAs) are small RNA molecules that regulate gene expression by targeting messenger RNAs (mRNAs) and causing mRNA cleavage or translation blockage. Of the 355 Arthropod miRNAs that have been identified, only 21 are B. mori miRNAs that were predicted computationally; of these, only let-7 has been confirmed by Northern blotting. RESULTS: Combining a computational method based on sequence homology searches with experimental identification based on microarray assays and Northern blotting, we identified 46 miRNAs, an additional 21 plausible miRNAs, and a novel small RNA in B. mori. The latter, bmo-miR-100-like, was identified using the known miRNA aga-miR-100 as a probe; bmo-miR-100-like was detected by microarray assay and Northern blotting, but its precursor sequences did not fold into a hairpin structure. Among these identified miRNAs, we found 12 pairs of miRNAs and miRNA*s. Northern blotting revealed that some B. mori miRNA genes were expressed only during specific stages, indicating that B. mori miRNA genes (e.g., bmo-miR-277) have developmentally regulated patterns of expression. We identified two miRNA gene clusters in the B. mori genome. bmo-miR-2b, which is found in the gene cluster bmo-miR-2a-1/bmo-miR-2a-1*/bmo-miR-2a-2/bmo-miR-2b/bmo-miR-13a*/bmo-miR-13b, encodes a newly identified member of the mir-2 family. Moreover, we found that methylation can increase the sensitivity of a DNA probe used to detect a miRNA by Northern blotting. Functional analysis revealed that 11 miRNAs may regulate 13 B. mori orthologs of the 25 known Drosophila miRNA-targeted genes according to the functional conservation. We predicted the binding sites on the 1671 3'UTR of B. mori genes; 547 targeted genes, including 986 target sites, were predicted. Of these target sites, 338 had perfect base pairing to the seed region of 43 miRNAs. From the predicted genes, 61 genes, each of them with multiple predicted target sites, should be considered excellent candidates for future functional studies. Biological classification of predicted miRNA targets showed that "binding", "catalytic activity" and "physiological process" were over-represented for the predicted genes. CONCLUSION: Combining computational predictions with microarray assays, we identified 46 B. mori miRNAs, 13 of which were miRNA*s. We identified a novel small RNA and 21 plausible B. mori miRNAs that could not be located in the available B. mori genome, but which could be detected by microarray. Thirteen and 547 target genes were predicted according to the functional conservation and binding sites, respectively. Identification of miRNAs in B. mori, particularly those that are developmentally regulated, provides a foundation for subsequent functional studies.

Analysis of similarity/dissimilarity of DNA sequences based on a class of 2D graphical representation.

On the basis of a class of 2D graphical representations of DNA sequences, sensitivity analysis has been performed, showing the high-capability of the proposed representations to take into account small modifications of the DNA sequences. And sensitivity analysis also indicates that the absolute differences of the leading eigenvalues of the L/L matrices associated with DNA increase with the increase of the number of the base mutations. Besides, we conclude that the similarity analysis method based on the correlation angles can better eliminate the effects of the lengths of DNA sequences if compared with the method using the Euclidean distances. As application, the examination of similarities/dissimilarities among the coding sequences of the first exon of beta-globin gene of different species has been performed by our method, and the reasonable results verify the validity of our method.

Complete sequence and organization of Antheraea pernyi nucleopolyhedrovirus, a dr-rich baculovirus.

BACKGROUND: The completion and reporting of baculovirus genomes is extremely important as it advances our understanding of gene function and evolution. Due to the large number of viral genomes now sequenced it is very important that authors present significantly detailed analyses to advance the understanding of the viral genomes. However, there is no report of the Antheraea pernyi nucleopolyhedrovirus (AnpeNPV) genome. RESULTS: The genome of AnpeNPV, which infects Chinese tussah silkworm (Antheraea pernyi), was sequenced and analyzed. The genome was 126,629 bp in size. The G+C content of the genome, 53.4%, was higher than that of most of the sequenced baculoviruses. 147 open reading frames (ORFs) that putatively encode proteins of 50 or more amino acid residues with minimal overlap were determined. Of the 147 ORFs, 143 appeared to be homologous to other baculovirus genes, and 4 were unique to AnpeNPV. Furthermore, there are still 29 and 33 conserved genes present in all baculoviruses and all lepidopteran baculoviruses respectively. In addition, the total number of genes common to all lepidopteran NPVs is sill 74, however the 74 genes are somewhat different from the 74 genes identified before because of some new sequenced NPVs. Only 6 genes were found exclusively in all lepidopteran NPVs and 12 genes were found exclusively in all Group I NPVs. AnpeNPV encodes v-trex(Anpe115, a 3' to 5' repair exonuclease), which was observed only in CfMNPV and CfDEFNPV in Group I NPVs. This gene potentially originated by horizontal gene transfer from an ancestral host. In addition, AnpeNPV encodes two conotoxin-like gene homologues (ctls), ctl1 and ctl2, which were observed only in HycuNPV, OpMNPV and LdMNPV. Unlike other baculoviruses, only 3 typical homologous regions (hrs) were identified containing 2~9 repeats of a 30 bp-long palindromic core. However, 24 perfect or imperfect direct repeats (drs) with a high degree of AT content were found within the intergenic spacer regions that may function as non-hr, ori-like regions found in GrleGV, CpGV and AdorGV. 9 drs were also found in intragenic spacer regions of AnpeNPV. CONCLUSION: AnpeNPV belongs to Group I NPVs and is most similar to HycuNPV, EppoNPV, OpMNPV and CfMNPV based on gene content, genome arrangement, and amino acid identity. In addition, analysis of genes that flank hrs supported the argument that these regions are involved in the transfer of sequences between the virus and host.