Distributed multi-objective optimization for SNP-SNP interaction detection.

The detection of complex interactions between single nucleotide polymorphisms (SNPs) plays a vital role in genome-wide association analysis (GWAS). The multi-objective evolutionary algorithm is a promising technique for SNP-SNP interaction detection. However, as the scale of SNP data further increases, the exponentially growing search space gradually becomes the dominant factor, causing evolutionary algorithm (EA)-based approaches to fall into local optima. In addition, multi-objective genetic operations consume significant amounts of time and computational resources. To this end, this study proposes a distributed multi-objective evolutionary framework (DM-EF) to identify SNP-SNP interactions on large-scale datasets. DM-EF first partitions the entire search space into several subspaces based on a space-partitioning strategy, which is nondestructive because it guarantees that each feasible solution is assigned to a specific subspace. Thereafter, each subspace is optimized using a multi-objective EA optimizer, and all subspaces are optimized in parallel. A decomposition-based multi-objective firework optimizer (DCFWA) with several problem-guided operators was designed. Finally, the final output is selected from the Pareto-optimal solutions in the historical search of each subspace. DM-EF avoids the preference for a single objective function, handles the heavy computational burden, and enhances the diversity of the population to avoid local optima. Notably, DM-EF is load-balanced and scalable because it can flexibly partition the space according to the number of available computational nodes and problem size. Experiments on both artificial and real-world datasets demonstrate that the proposed method significantly improves the search speed and accuracy.

Dynamical modelling of viral infection and cooperative immune protection in COVID-19 patients.

Once challenged by the SARS-CoV-2 virus, the human host immune system triggers a dynamic process against infection. We constructed a mathematical model to describe host innate and adaptive immune response to viral challenge. Based on the dynamic properties of viral load and immune response, we classified the resulting dynamics into four modes, reflecting increasing severity of COVID-19 disease. We found the numerical product of immune system's ability to clear the virus and to kill the infected cells, namely immune efficacy, to be predictive of disease severity. We also investigated vaccine-induced protection against SARS-CoV-2 infection. Results suggested that immune efficacy based on memory T cells and neutralizing antibody titers could be used to predict population vaccine protection rates. Finally, we analyzed infection dynamics of SARS-CoV-2 variants within the construct of our mathematical model. Overall, our results provide a systematic framework for understanding the dynamics of host response upon challenge by SARS-CoV-2 infection, and this framework can be used to predict vaccine protection and perform clinical diagnosis.

Accurately Computing the Interacted Volume of Molecules over Their 3D Mesh Models.

For quickly predicting the rational arrangement of catalysts and substrates, we previously proposed a method to calculate the interacted volumes of molecules over their 3D point cloud models. However, the nonuniform density in molecular point clouds may lead to incomplete contours in some slices, reducing the accuracy of the previous method. In this paper, we propose a two-step method for more accurately computing molecular interacted volumes. First, by employing a prematched mesh slicing method, we layer the 3D triangular mesh models of the electrostatic potential isosurfaces of two molecules globally, transforming the volume calculation into finding the intersecting areas in each layer. Next, by subdividing polygonal edges, we accurately identify intersecting parts within each layer, ensuring precise calculation of interacted volumes. In addition, we present a concise overview for computing intersecting areas in cases of multiple contour intersections and for improving computational efficiency by incorporating bounding boxes at three stages. Experimental results demonstrate that our method maintains high accuracy in different experimental data sets, with an average relative error of 0.16%. On the same experimental setup, our average relative error is 0.07%, which is lower than the previous algorithm's 1.73%, improving the accuracy and stability in calculating interacted volumes.

A rapidly reversible mutation generates subclonal genetic diversity and unstable drug resistance.

Most genetic changes have negligible reversion rates. As most mutations that confer resistance to an adverse condition (e.g., drug treatment) also confer a growth defect in its absence, it is challenging for cells to genetically adapt to transient environmental changes. Here, we identify a set of rapidly reversible drug-resistance mutations in Schizosaccharomyces pombe that are caused by microhomology-mediated tandem duplication (MTD) and reversion back to the wild-type sequence. Using 10,000× coverage whole-genome sequencing, we identify nearly 6,000 subclonal MTDs in a single clonal population and determine, using machine learning, how MTD frequency is encoded in the genome. We find that sequences with the highest-predicted MTD rates tend to generate insertions that maintain the correct reading frame, suggesting that MTD formation has shaped the evolution of coding sequences. Our study reveals a common mechanism of reversible genetic variation that is beneficial for adaptation to environmental fluctuations and facilitates evolutionary divergence.

Stappia sediminis sp. nov., isolated from rhizosphere soil of coastal herb Zoysia matrella within the Beibu Gulf.

A bacterial isolate (BGMRC 2046T) was isolated from the rhizosphere soil of Zoysia matrella collected from the Beibu Gulf of China. The results of a polyphasic taxonomic study revealed that this strain belongs to a member of the genus Stappia with the characteristics of Gram-stain-negative, catalase- and oxidase-positive, motile, short rod-shaped. The strain grew at 20-37 °C (optimal, 28 °C), pH 6.0-9.0 (optimal, pH 7.0), and 1-7% (w/v) optimal, NaCl (1-3%). A phylogenetic evaluation based on 16S rRNA gene sequence analysis revealed that this strain fall into the family Stappiaceae, being most closely related to Stappia indica CGMCC 1A01226T (95.8% sequence similarity), Stappia stellulata DSM 5886T (95.1%), and Stappia taiwanensis DSM 23284T (94.4%). The major cellular fatty acid, respiratory quinone and polar lipids were all detected from new species (BGMRC 2046T), that shows the chemical characteristics of BGMRC 2046T. The major polar lipids were two unidentified ninhydrin positive phospholipids, four unidentified phospholipids, and one unidentified lipid. Genome sequencing revealed a genome size of 4.78 Mbp and a G + C content of 60.8%. Pairwise comparison of the genomes of the new strain BGMRC 2046T and the three most closely related strains resulted in gANI values was lower than 75% and a digital DNA-DNA hybridization values was lower than 24%. The strain possessed genes encoding choline uptake and conversion to betaine gene clusters. The results of the polyphasic taxonomic study showed that strain BGMRC 2046T represents a new species of the genus Stappia. The name Stappia sediminis sp. nov. is proposed for the species with the type strain BGMRC 2046T (= KCTC52115T = CGMCC1.17425T).

Rapid Quantification of Polyhydroxyalkanoates Accumulated in Living Cells Based on Green Fluorescence Protein-Labeled Phasins: The qPHA Method.

Polyhydroxyalkanoates (PHAs) are microbial polyesters that have the potential to replace nonbiodegradable petroplastics. A real-time in situ PHA quantification method has long been awaited to replace the traditional method, which is time- and labor-consuming. Quantification of PHA in living cells was finally developed from fluorescence intensities generated from the green fluorescence protein (GFP) fused with the Halomonas bluephagenesis phasin proteins. Phasins PhaP1 and PhaP2 were used to fuse with GFP, which reflected PHA accumulation with an R-square of over 0.9. Also, a standard correlation was established to calculate PHA contents based on the fluorescence and cell density recorded via a microplate reader with an R-square of over 0.95 when grown on various substrates. The PhaP2-GFP containing H. bluephagenesis was applied successfully to quantify PHA synthesis in a 7.5 L fermenter with high precision. Moreover, the method was found to be feasible in non-natural PHA producers such as Escherichia coli, demonstrating its broad applicability.

Corneal nerve structure in patients with primary Sjögren's syndrome in China.

BACKGROUND: The aim of this study was to evaluate the in vivo confocal microscopic morphology of corneal subbasal nerves and its relationship with clinical parameters in patients with primary Sjögren's syndrome in China. METHODS: This was a case control study of 22 dry eye disease (DED) patients with primary Sjögren's syndrome (pSS) and 20 control subjects with non-Sjögren dry eye disease (NSDE). Each patient underwent an evaluation of ocular surface disease using the tear film break-up time (TBUT), noninvasive tear film break-up time (NIKBUT), noninvasive tear meniscus height (NIKTMH), corneal staining (National Eye Institute scale, NEI), Schirmer I test, meibography, and corneal subbasal nerve analysis with in vivo confocal microscopy (IVCM). The right eye of each subject was included in this study. RESULTS: SS patients showed a shorter TBUT (P = 0.009) and Schirmer I test results (P = 0.028) than the NSDE group. However, there was no significant difference in NIKBUT between the two groups (P = 0.393). The nerve density of subbasal nerves, number of nerves and tortuosity of the SS group were significantly lower than those of the NSDE group (P = 0.001, P < 0.001 and P = 0.039, respectively). In the SS group, the mean nerve length was correlated with age and the Schirmer I test (r = - 0.519, P = 0.013 and r = 0.463, P = 0.035, respectively). Corneal staining was correlated with nerve density and the number of nerves (r = - 0.534, P = 0.013 and r = - 0.487, P = 0.025, respectively). CONCLUSIONS: Sjögren syndrome dry eye (SSDE) patients have more severe clinical dry eye parameters than non-Sjögren dry eye disease (NSDE) patients. Compared with NSDE patients, we found that SSDE patients showed decreased corneal subbasal nerve density and numbers.

Block Adjustment without GCPs for Chinese Spaceborne SAR GF-3 Imagery.

The Gaofen-3 (GF-3) satellite is the first C-band multi-polarization synthetic aperture radar (SAR) with the ability of high-accuracy mapping in China. However, the Ground Control Points (GCPs) are essential to ensure the accuracy of mapping for GF-3 SAR imagery at present. In this paper, we analyze the error sources that affect the geometric processing and propose a new block adjustment method without GCPs for GF-3 SAR imagery. Firstly, the geometric calibration of GF-3 image is carried out. Secondly, the rational polynomial coefficient (RPC) model is directly generated after the geometric calibration parameters compensation of each image. Finally, we solve the orientation parameters of the GF-3 images through DEM assisted planar block adjustment and conduct ortho-rectification. With two different imaging modes of GF-3 satellite, which include the QPSI and FS2, we carry out the block adjustment without GCPs. Experimental results of testing areas including Wuhan city and Hubei province in China show that the geometric mosaic accuracy and the absolute positioning accuracy of the orthophoto are better than one pixel, which has laid a good foundation for the application of GF-3 image in global high-accuracy mapping.

Energy landscape reveals that the budding yeast cell cycle is a robust and adaptive multi-stage process.

Quantitatively understanding the robustness, adaptivity and efficiency of cell cycle dynamics under the influence of noise is a fundamental but difficult question to answer for most eukaryotic organisms. Using a simplified budding yeast cell cycle model perturbed by intrinsic noise, we systematically explore these issues from an energy landscape point of view by constructing an energy landscape for the considered system based on large deviation theory. Analysis shows that the cell cycle trajectory is sharply confined by the ambient energy barrier, and the landscape along this trajectory exhibits a generally flat shape. We explain the evolution of the system on this flat path by incorporating its non-gradient nature. Furthermore, we illustrate how this global landscape changes in response to external signals, observing a nice transformation of the landscapes as the excitable system approaches a limit cycle system when nutrients are sufficient, as well as the formation of additional energy wells when the DNA replication checkpoint is activated. By taking into account the finite volume effect, we find additional pits along the flat cycle path in the landscape associated with the checkpoint mechanism of the cell cycle. The difference between the landscapes induced by intrinsic and extrinsic noise is also discussed. In our opinion, this meticulous structure of the energy landscape for our simplified model is of general interest to other cell cycle dynamics, and the proposed methods can be applied to study similar biological systems.

ANALYSIS OF CHANGES IN CHARACTERISTICS OF SEVERE RETINOPATHY OF PREMATURITY PATIENTS AFTER SCREENING GUIDELINES WERE ISSUED IN CHINA.

PURPOSE: To describe the changes in the characteristics of infants treated for severe retinopathy of prematurity (ROP) in a tertiary referral unit in China after screening guidelines were issued in 2004 and to evaluate the effectiveness of the current criteria. METHODS: Information on consecutive infants referred to a single eye department for treatment of Stage 3 (Type 1 pretheshold and threshold disease), Stage 4, and Stage 5 ROP between January 2001 and May 2012 was retrieved from medical records. RESULTS: The mean gestational age was 29.98 ± 2.13 weeks (range 26-34 weeks), and the mean birth weight was 1,414.32 ± 343.18 g (range 742-2,087 g). The proportion of infants with Stage 4 and Stage 5 ROP decreased statistically significantly over time (P = 0.026 and P < 0.001, respectively) after screening guidelines for ROP were issued in 2004. The median postmenstrual age when patients first visited the study hospital was 48.32 weeks (range 30-602 weeks); later presentation was significantly associated with more advanced ROP (P < 0.001). In addition, the postmenstrual age of first presentation showed a significant decrease over time (P < 0.001) after the screening guidelines were issued. The current Chinese screening guidelines cover 99.63% of infants while 9.07% of infants exceeded the U.K. screening criteria and 35.77% of infants exceeded the U.S. criteria. CONCLUSION: After the government issued guidelines on ROP screening, the birth weight and gestational age of severe ROP patients remain similar. Big infants got severe ROP as before. But the awareness of ROP increased, the proportion of infants with retinal detachment caused by ROP decreased, and the infants received more timely treatment. The current ROP screening criteria are very effective.

Quercetin inhibits vascular endothelial growth factor-induced choroidal and retinal angiogenesis in vitro.

PURPOSE: The aim of this study was to investigate the effects of quercetin on vascular endothelial growth factor (VEGF)-induced choroidal and retinal angiogenesis in vitro using a rhesus macaque choroid-retinal endothelial (RF/6A) cell line. METHODS: RF/6A cells were cultured in Dulbecco's modified Eagle's medium containing 10% fetal bovine serum. Then the cells were treated with different concentrations (from 0 to 100 µM) of quercetin and 100 ng/ml VEGF. The cell proliferation was assessed using cholecystokinin octapeptide dye. The cell migration was investigated by a Transwell assay. The tube formation was measured on Matrigel. Furthermore, the impact of quercetin's effects on VEGF-induced activation of VEGF receptor 2 (VEGFR-2) downstream signal pathways was tested by Western blot analysis. RESULTS: Quercetin inhibits RF/6A cell proliferation in a dose-dependent fashion: 22.7, 31.5 and 36.7% inhibition on treatment with 10, 50 and 100 µM quercetin, respectively. VEGF-induced migration and tube formation of RF/6A cells were also significantly inhibited by quercetin in a dose-dependent manner. Quercetin inhibits VEGF-induced VEGFR-2 downstream signal pathways of RF/6A. CONCLUSIONS: The results show that quercetin inhibits VEGF-induced cell proliferation, migration and tube formation of RF/6A. We suggest that quercetin inhibits VEGF-induced choroidal and retinal angiogenesis in vitro. Collectively, the findings in the present study suggest that quercetin inhibits VEGF-induced choroidal and retinal angiogenesis by targeting the VEGFR-2 pathway. This suggests that quercetin is a choroidal and retinal angiogenesis inhibitor.

[Suppression of retinal angiogenesis by quercetin in a rodent model of retinopathy of prematurity].

OBJECTIVE: To determine whether quercetin can suppress retinal angiogenesis in a rodent model of retinopathy of prematurity (ROP). METHODS: ROP was induced in C57BL/6 mice by exposing 7-day-old mice to 75% oxygen (hyperoxia) for 5 days followed by 5 days in room air. Quercetin (20 mg/kg body weight) was administered intraperitoneally from Days 12-17. Control group received an intraperitoneal dose of propylene glycol. At Day 17, the eyes were enucleated and retinae diseected for ADPase and hematoxylin and eosin staining. The severity of neovsascularization were graded as the number of clock hour of new vessel (NV) with a masked approach. The proliferative neovascular response was quantifled by counting the nuclei of new vessels extending from retina into vitreous in cross-sections. And vascular endothelial growth factor (VEGF) was detected by enzyme-linked immunosorbent assay (ELISA). RESULTS: The severity of NV decreased significantly in Quercetin treatment group versus control group (P<0.05). The number of endothelial cells of new vessels extending from retina to viueous decreased significantly in quercetin treatment group versus hyperoxia group (P<0.05). The retinal level of VEGF decreased significantly in quercetin treatment group. CONCLUSION: Quercetin attenuates retinal angiogenesis so that it may become a potential preventive chemotherapy for ROP.

[The efficiency of 810 nm diode laser photocoagulation for type1 retinopathy of prematurity].

OBJECTIVE: To evaluate diode laser photocoagulation effects in type 1 prethreshold retinopathy of prematurity (ROP) in Peking University People's Hospital. METHODS: Retrospective cross-sectional study. Clinical records of the premature infants treated for type 1 prethreshold ROP from the year of 2008 to 2012 were reviewed. RESULTS: We reviewed 226 infants including 146 male and 80 female. The mean birth weight and the gestational age were 1 386 grams and 30.2 weeks respectively. In all the 384 photocoagulation treated eyes, ROP regressed completely in 381 eyes (99.1%). One eye of zone I ROP progressed to stage 4A. Macula kept attaching after vitrectomy. There was no significant difference of regression rate between Zone I and Zone II of type 1 prethreshold ROP. No severe complications occurred. CONCLUSIONS: Diode laser photocoagulation in type 1 ROP was safe and efficient.

ABCA1 rs1883025 polymorphism shows no association with neovascular age-related macular degeneration or polypoidal choroidal vasculopathy in a Northern Chinese population.

PURPOSE: To analyze the association between ABCA1 rs1883025 variants with neovascular age-related macular degeneration (nAMD) and polypoidal choroidal vasculopathy (PCV) in a northern Chinese population. METHODS: The study enrolled 900 subjects, including 300 controls, 300 cases with nAMD and 300 cases with PCV. Genomic DNA was extracted from venous blood leukocytes. Single-nucleotide polymorphisms in the ABCA1 (rs1883025) gene were genotyped by matrix-assisted laser desorption/ionization time-of-flight mass spectrometry. RESULTS: The ABCA1 rs1883025 polymorphism was not significantly associated with nAMD (22.5%; p > 0.05) or PCV (20.8%; p > 0.05) in a northern Chinese population. The association remained insignificant after adjustment for age and gender differences (p > 0.05). CONCLUSIONS: This study suggests that ABCA1 rs1883025 variants are not associated with nAMD or PCV in a Chinese population, which is likely due to an ethnic difference.

Repeat biopsy versus initial biopsy in terms of complication risk factors and clinical outcomes for patients with non-small cell lung cancer: a comparative study of 113 CT-guided needle biopsy of lung lesions.

Objectives: The safety and feasibility of repeat biopsy after systemic treatment for non-small cell lung cancer have received extensive attention in recent years. The purpose of this research was to compare complication rates between initial biopsy and rebiopsy in non-small cell lung cancer patients with progressive disease and to assess complication risk factors and clinical results after rebiopsy. Methods: The study included 113 patients initially diagnosed with non-small cell lung cancer who underwent lung biopsy at initial biopsy and rebiopsy after progression while on epidermal growth factor receptor tyrosine kinase inhibitors (EGFR-TKIs) and/or chemotherapy from January 2018 to December 2021. We compared the incidence of complications between the initial biopsy and rebiopsy and analyzed the predictors factors that influenced complications in patients who underwent rebiopsy. Results: The successful rate of rebiopsy was 88.5% (100/113). With the exception of two cases where lung adenocarcinoma changed into small cell lung cancer with gefitinib treatment, 98 individuals retained their initial pathological type. The secondary EGFR T790M mutation accounts for 55.6% of acquired resistance. The total number of patients with complications in initial biopsy was 25 (22.1%) and 37 (32.7%) in the rebiopsy. The incidence of pulmonary hemorrhage increased from 7.1% at the initial biopsy to 10.6% at rebiopsy, while the incidence of pneumothorax increased from 14.2% to 20.4%. Compared with the initial biopsy, the incidence of overall complications, parenchymal hemorrhage, and pneumothorax increased by 10.6%, 3.5%, and 6.2%, respectively. In all four evaluations (pneumorrhagia, pneumothorax, pleural reaction, and overall complication), there were no significant differences between the rebiopsy and initial biopsy (all p > 0.05). The multivariate logistic regression analysis suggested that male sex (odds ratio [OR] = 5.064, p = 0.001), tumor size ≤ 2 cm (OR = 3.367, p = 0.013), EGFR-TKIs with chemotherapy (OR = 3.633, p =0.023), and transfissural approach (OR = 7.583, p = 0.026) were independent risk factors for overall complication after rebiopsy. Conclusion: Compared with the initial biopsy, the complication rates displayed a slight, but not significant, elevation in rebiopsy. Male sex, tumor size ≤ 2 cm, transfissural approach, and EGFR-TKIs combined with chemotherapy were independent risk factors for rebiopsy complications.

Hypopyon after Periocular Corticosteroid Injection: A Case Series.

PURPOSE: The purpose of this study was to describe a case series of hypopyon after periorbital corticosteroid injection. METHODS: This was a retrospective, observational case series investigating hypopyon cases after injection of periorbital steroid patients. RESULTS: We presented three patients manifested hypopyon after periocular corticosteroid injection. All three cases were diagnosed as HSV stromal keratitis or endotheliitis and treated successfully with topical steroids as well as systemic and topical antiviral treatment. CONCLUSION: HSV keratitis is not recommend when treated with periocular corticosteroid injection. Topical corticosteroid is the best choice for HSV stromal keratitis and HSV endotheliitis.

The multiple activations in budding yeast S-phase checkpoint are Poisson processes.

Eukaryotic cells activate the S-phase checkpoint signal transduction pathway in response to DNA replication stress. Affected by the noise in biochemical reactions, such activation process demonstrates cell-to-cell variability. Here, through the analysis of microfluidics-integrated time-lapse imaging, we found multiple S-phase checkpoint activations in a certain budding yeast cell cycle. Yeast cells not only varied in their activation moments but also differed in the number of activations within the cell cycle, resulting in a stochastic multiple activation process. By investigating dynamics at the single-cell level, we showed that stochastic waiting times between consecutive activations are exponentially distributed and independent from each other. Finite DNA replication time provides a robust upper time limit to the duration of multiple activations. The mathematical model, together with further experimental evidence from the mutant strain, revealed that the number of activations under different levels of replication stress agreed well with Poisson distribution. Therefore, the activation events of S-phase checkpoint meet the criterion of Poisson process during DNA replication. In sum, the observed Poisson activation process may provide new insights into the complex stochastic dynamics of signal transduction pathways.

Case Report: A Rare Fungal Keratitis Caused by Plectosphaerella Cucumerina.

PURPOSE: To report a rare case of fungal keratitis caused by Plectosphaerella cucumerina. METHODS: This study retrospectively reviewed the medical records of a case of fungal keratitis. RESULTS: Silt-lamp biomicroscopy revealed corneal infiltration and epithelial defects. Anterior segment optical coherence tomography (AS-OCT) and in vivo confocal microscopy (IVCM) were performed to assist in the diagnosis and evaluate corneal conditions. The isolate was identified as Plectosphaerella cucumerina by MALDI-TOF mass spectrometry. The patient was treated with topical 5% pimaricin and oral voriconazole for 1 month and recovered. CONCLUSION: Fungal keratitis caused by Plectosphaerella cucumerina is rare. AS-OCT and IVCM can help locate the lesion and diagnose fungal keratitis. Furthermore, MALDI-TOF mass spectrometry showed potential prospects in the identification of filamentous fungi. Plectosphaerella cucumerina rarely infects humans and is sensitive to antifungal agents such as pimaricin and voriconazole.

CT radiomics model for predicting the Ki-67 proliferation index of pure-solid non-small cell lung cancer: a multicenter study.

Purpose: This study aimed to explore the efficacy of the computed tomography (CT) radiomics model for predicting the Ki-67 proliferation index (PI) of pure-solid non-small cell lung cancer (NSCLC). Materials and methods: This retrospective study included pure-solid NSCLC patients from five centers. The radiomics features were extracted from thin-slice, non-enhanced CT images of the chest. The minimum redundancy maximum relevance (mRMR) and least absolute shrinkage and selection operator (LASSO) were used to reduce and select radiomics features. Logistic regression analysis was employed to build predictive models to determine Ki-67-high and Ki-67-low expression levels. Three prediction models were established: the clinical model, the radiomics model, and the nomogram model combining the radiomics signature and clinical features. The prediction efficiency of different models was evaluated using the area under the curve (AUC). Results: A total of 211 NSCLC patients with pure-solid nodules or masses were included in the study (N=117 for the training cohort, N=49 for the internal validation cohort, and N=45 for the external validation cohort). The AUC values for the clinical models in the training, internal validation, and external validation cohorts were 0.73 (95% CI: 0.64-0.82), 0.75 (95% CI:0.62-0.89), and 0.72 (95% CI: 0.57-0.86), respectively. The radiomics models showed good predictive ability in diagnosing Ki-67 expression levels in the training cohort (AUC, 0.81 [95% CI: 0.73-0.89]), internal validation cohort (AUC, 0.81 [95% CI: 0.69-0.93]) and external validation cohort (AUC, 0.78 [95% CI: 0.64-0.91]). Compared to the clinical and radiomics models, the nomogram combining both radiomics signatures and clinical features had relatively better diagnostic performance in all three cohorts, with the AUC of 0.83 (95% CI: 0.76-0.90), 0.83 (95% CI: 0.71-0.94), and 0.81 (95% CI: 0.68-0.93), respectively. Conclusion: The nomogram combining the radiomics signature and clinical features may be a potential non-invasive method for predicting Ki-67 expression levels in patients with pure-solid NSCLC.

Modular analysis of the probabilistic genetic interaction network.

MOTIVATION: Epistatic Miniarray Profiles (EMAP) has enabled the mapping of large-scale genetic interaction networks; however, the quantitative information gained from EMAP cannot be fully exploited since the data are usually interpreted as a discrete network based on an arbitrary hard threshold. To address such limitations, we adopted a mixture modeling procedure to construct a probabilistic genetic interaction network and then implemented a Bayesian approach to identify densely interacting modules in the probabilistic network. RESULTS: Mixture modeling has been demonstrated as an effective soft-threshold technique of EMAP measures. The Bayesian approach was applied to an EMAP dataset studying the early secretory pathway in Saccharomyces cerevisiae. Twenty-seven modules were identified, and 14 of those were enriched by gold standard functional gene sets. We also conducted a detailed comparison with state-of-the-art algorithms, hierarchical cluster and Markov clustering. The experimental results show that the Bayesian approach outperforms others in efficiently recovering biologically significant modules.