A gray box framework that optimizes a white box logical model using a black box optimizer for simulating cellular responses to perturbations.

Predicting cellular responses to perturbations requires interpretable insights into molecular regulatory dynamics to perform reliable cell fate control, despite the confounding non-linearity of the underlying interactions. There is a growing interest in developing machine learning-based perturbation response prediction models to handle the non-linearity of perturbation data, but their interpretation in terms of molecular regulatory dynamics remains a challenge. Alternatively, for meaningful biological interpretation, logical network models such as Boolean networks are widely used in systems biology to represent intracellular molecular regulation. However, determining the appropriate regulatory logic of large-scale networks remains an obstacle due to the high-dimensional and discontinuous search space. To tackle these challenges, we present a scalable derivative-free optimizer trained by meta-reinforcement learning for Boolean network models. The logical network model optimized by the trained optimizer successfully predicts anti-cancer drug responses of cancer cell lines, while simultaneously providing insight into their underlying molecular regulatory mechanisms.

Decoding the principle of cell-fate determination for its reverse control.

Understanding and manipulating cell fate determination is pivotal in biology. Cell fate is determined by intricate and nonlinear interactions among molecules, making mathematical model-based quantitative analysis indispensable for its elucidation. Nevertheless, obtaining the essential dynamic experimental data for model development has been a significant obstacle. However, recent advancements in large-scale omics data technology are providing the necessary foundation for developing such models. Based on accumulated experimental evidence, we can postulate that cell fate is governed by a limited number of core regulatory circuits. Following this concept, we present a conceptual control framework that leverages single-cell RNA-seq data for dynamic molecular regulatory network modeling, aiming to identify and manipulate core regulatory circuits and their master regulators to drive desired cellular state transitions. We illustrate the proposed framework by applying it to the reversion of lung cancer cell states, although it is more broadly applicable to understanding and controlling a wide range of cell-fate determination processes.

Incidence of intraoperative hypotension in older patients undergoing total intravenous anesthesia by remimazolam versus propofol: A randomized controlled trial.

BACKGROUND: An increase in the frequency of surgeries among older individuals is observed in some countries. Hypotension is common and exaggerated in older patients and can lead to increased morbidity and mortality. Total intravenous anesthesia is commonly administered with propofol, while remimazolam has been suggested as an alternative to propofol because of advantages such as a more stable hemodynamic profile and less respiratory suppression. We conducted a single-blind, parallel-group randomized controlled trial to compare the incidence of intraoperative hypotension between patients administered with remimazolam and propofol. METHODS: A total of 132 patients, aged between 65 to 80 years and undergoing laparoscopic cholecystectomy or transurethral resection of bladder tumors were randomly assigned to the propofol or remimazolam group with a permuted block system while being blinded to the hypnotic agent. Remifentanil was administered via target-controlled infusion in both groups, with an initial effect-site concentration of 3.0 ng/mL and titration range of 1.5 to 4.0 ng/mL intraoperatively. The primary outcome of this study was the overall incidence of hypotension during general anesthesia. RESULTS: Patients in the propofol group experienced higher intraoperative hypotension than those in the remimazolam group (59.7% vs 33.3%, P = .006). Multivariate logistic regression analysis showed that remimazolam administration was associated with reduced hypotension (adjusted odds ratio, 0.34; 95% CI, 0.16-0.73). Secondary outcomes such as recovery time, delirium, and postoperative nausea and vomiting were comparable in both groups. CONCLUSION: Total intravenous anesthesia with remimazolam was associated with less intraoperative hypotension than propofol in older patients, with a comparable recovery profile.

Genomic insight into the salt tolerance and proteolytic activity of Bacillus subtilis.

We assessed the salt tolerance and proteolytic activity of 40 genome-published Bacillus subtilis strains isolated from fermented Korean foods to illuminate the genomic background behind the functionality of B. subtilis in high-salt fermentation. On the basis of the salt tolerance and phenotypic proteolytic activity of the 40 strains, we selected five strains exhibiting different phenotypic characteristics. Comparative genomic analyses of these five strains provided genomic insight into the salt tolerance and proteolytic activity of B. subtilis. Two-component system (TCS) genes annotated as ybdGJK and laterally acquired authentic ATP-binding cassette (ABC) transporter system genes of tandem repeat structure might contribute to increase salt tolerance. The additional possession of gene homologs for CAAX protease family proteins and components of Clp (caseinolytic protease) complex, ATP-dependent Clp proteolytic subunit ClpP and AAA+ (ATPases associated with diverse cellular Activities) family ATPases, might determine the proteolytic activity of B. subtilis. This study established the scientific foundation for the viability and functionality of B. subtilis in high-salt fermentation.

A Study on Survival Analysis Methods Using Neural Network to Prevent Cancers.

Background: Cancer is one of the main global health threats. Early personalized prediction of cancer incidence is crucial for the population at risk. This study introduces a novel cancer prediction model based on modern recurrent survival deep learning algorithms. Methods: The study includes 160,407 participants from the blood-based cohort of the Korea Cancer Prevention Research-II Biobank, which has been ongoing since 2004. Data linkages were designed to ensure anonymity, and data collection was carried out through nationwide medical examinations. Predictive performance on ten cancer sites, evaluated using the concordance index (c-index), was compared among nDeep and its multitask variation, Cox proportional hazard (PH) regression, DeepSurv, and DeepHit. Results: Our models consistently achieved a c-index of over 0.8 for all ten cancers, with a peak of 0.8922 for lung cancer. They outperformed Cox PH regression and other survival deep neural networks. Conclusion: This study presents a survival deep learning model that demonstrates the highest predictive performance on censored health dataset, to the best of our knowledge. In the future, we plan to investigate the causal relationship between explanatory variables and cancer to reduce cancer incidence and mortality.

Clinical Outcomes of Upfront Primary Tumor Resection in Synchronous Unresectable Metastatic Colorectal Cancer.

The role of upfront primary tumor resection (PTR) in patients with unresectable metastatic colorectal cancer without severe symptoms remains controversial. We retrospectively analyzed the role of PTR in overall survival (OS) in this population. Among the 205 patients who enrolled, the PTR group (n = 42) showed better performance (p = 0.061), had higher frequencies of right-sided origin (p = 0.058), the T4 stage (p = 0.003), the M1a stage (p = 0.012), and <2 organ metastases (p = 0.002), and received fewer targeted agents (p = 0.011) than the chemotherapy group (n = 163). The PTR group showed a trend for longer OS (20.5 versus 16.0 months, p = 0.064) but was not related to OS in Cox regression multivariate analysis (p = 0.220). The male sex (p = 0.061), a good performance status (p = 0.078), the T3 stage (p = 0.060), the M1a stage (p = 0.042), <2 organ metastases (p = 0.035), an RAS wild tumor (p = 0.054), and the administration of targeted agents (p = 0.037), especially bevacizumab (p = 0.067), seemed to be related to PTR benefits. Upfront PTR could be considered beneficial in some subgroups, but these findings require larger studies to verify.

Transcriptomic analysis of Staphylococcus equorum KM1031 from the high-salt fermented seafood jeotgal under chloramphenicol, erythromycin and lincomycin stresses.

Staphylococcus equorum strain KM1031 is resistant to chloramphenicol, erythromycin and lincomycin. To shed light on the genetic factors underlying these antibiotic resistances, we determined the global gene expression profile of S. equorum KM1031 using RNA sequencing. During chloramphenicol, erythromycin and lincomycin treatment, 8.3% (183/2,336), 16.0% (354/2,336), and 2.9% (63/2,336) of S. equorum KM1031 genes exhibited significant differences in expression, respectively. These three antibiotics upregulated genes related to efflux and downregulated genes related to transporters. Antibiotic treatment also upregulated osmoprotectant-related genes involved in salt tolerance. To identify specific genes functionally related to antibiotic resistance, we compared the genome of strain KM1031 with those of three S. equorum strains that are sensitive to these three antibiotics. We identified three genes of particular interest: an antibiotic biosynthesis monooxygenase gene (abm, AWC34_RS01805) related to chloramphenicol resistance, an antibiotic ABC transporter ATP-binding protein gene (msr, AWC34_RS11115) related to erythromycin resistance, and a lincosamide nucleotydyltransferase gene (lnuA, AWC34_RS13300) related to lincomycin resistance. These genes were upregulated in response to the corresponding antibiotic; in particular, msr was upregulated more than fourfold by erythromycin treatment. Finally, the results of RNA sequencing were validated by quantitative real-time PCR. This transcriptomic analysis provides genetic evidence regarding antibiotic stress responses of S. equorum strain KM1031.

Network Dynamics Caused by Genomic Alteration Determine the Therapeutic Response to FGFR Inhibitors for Lung Cancer.

Recently, FGFR inhibitors have been highlighted as promising targeted drugs due to the high prevalence of FGFR1 amplification in cancer patients. Although various potential biomarkers for FGFR inhibitors have been suggested, their functional effects have been shown to be limited due to the complexity of the cancer signaling network and the heterogenous genomic conditions of patients. To overcome such limitations, we have reconstructed a lung cancer network model by integrating a cell line genomic database and analyzing the model in order to understand the underlying mechanism of heterogeneous drug responses. Here, we identify novel genomic context-specific candidates that can increase the efficacy of FGFR inhibitors. Furthermore, we suggest optimal targets that can induce more effective therapeutic responses than that of FGFR inhibitors in each of the FGFR-resistant lung cancer cells through computational simulations at a system level. Our findings provide new insights into the regulatory mechanism of differential responses to FGFR inhibitors for optimal therapeutic strategies in lung cancer.

Surface energetics of graphene oxide and reduced graphene oxide determined by inverse gas chromatographic technique at infinite dilution at room temperature.

Graphene is of great interest for many far-reaching applications that involve interparticle interactions in adsorbents, coatings, and composites. A deep understanding of the surface components has been crucial but achieving the most accurate and reliable values of these, unaffected by experimental conditions or the analytical techniques used, remains a major challenge. To this end, we have proposed in this paper a novel approach for the first time, to the best of our knowledge, to determine London dispersive and specific (polar) components including the Lewis acid-base character of the surface free energy of graphene materials (graphene oxide (GO), reduced graphene oxide (rGO), and graphite) using inverse gas chromatography (IGC) technique at an infinite dilution. We have estimated the London dispersive surface energy values of graphite, GO, and rGO as van der Waals interaction to be 156-179, 89-106, and 110-119 mJ m-2, respectively, in the temperature range of 320-360 K. These are attributable to the surface properties impacted by the oxygen moieties, defects, and micropores on the carbon frameworks. Further, the acceptor (KA) and donor (KD) parameters of GO were found to be 0.71 and 0.96, respectively, while those of rGO were 0.54 and 1.05. Notably, the GO is more of the Lewis acid character that could be amphoteric, while the Lewis base characteristics of both GO and rGO are not significantly changed. These results provide foundational knowledge to understand the physicochemical properties of graphene surfaces, which should be helpful to designing interface engineering in various applications.

Effect of intramuscular midazolam premedication on patient satisfaction in women undergoing general anaesthesia: a randomised control trial.

OBJECTIVE: To determine the effect of premedication with intramuscular midazolam on patient satisfaction in women undergoing general anaesthesia. TRIAL DESIGN, SETTING AND PARTICIPANTS: Double-blind, parallel randomised control trial at a tertiary care medical centre in South Korea. Initially, 140 women aged 20-65 years who underwent general anaesthesia and had an American Society of Anesthesiology physical status classification of I or II were randomly assigned to the intervention group or the control group, and 134 patients (intervention n=65; control n=69) completed the study. INTERVENTION: Intramuscular administration of midazolam (0.05 mg/kg) or placebo (normal saline 0.01 mL/kg) on arrival at the preoperative holding area. MAIN OUTCOMES: The primary outcome was the patient's overall satisfaction with the anaesthesia experience as determined by questionnaire responses on the day after surgery. Satisfaction was defined as a response of 3 or 4 on a five-point scale (0-4). The secondary outcomes included blood pressure, heart rate, oxygen desaturation, recovery duration and postoperative pain. RESULTS: Patients who received midazolam were more satisfied than those who received placebo (percentage difference: 21.0%, OR 3.56, 95% CI 1.46 to 8.70). A subgroup analysis revealed that this difference was greater in patients with anxiety, defined as those whose Amsterdam Preoperative Anxiety and Information Scale anxiety score was ≥11, than that for the whole sample population (percentage difference: 24.0%, OR 4.33, 95% CI 1.25 to 14.96). Both groups had similar heart rates, blood pressure and oxygen desaturation. CONCLUSION: Intramuscular administration of midazolam in women before general anaesthesia in the preoperative holding area improved self-reported satisfaction with the anaesthesia experience, with an acceptable safety profile. TRIAL REGISTRATION NUMBER: KCT0006002.

Network Analysis Identifies Regulators of Basal-Like Breast Cancer Reprogramming and Endocrine Therapy Vulnerability.

Basal-like breast cancer is the most aggressive breast cancer subtype with the worst prognosis. Despite its high recurrence rate, chemotherapy is the only treatment for basal-like breast cancer, which lacks expression of hormone receptors. In contrast, luminal A tumors express ERα and can undergo endocrine therapy for treatment. Previous studies have tried to develop effective treatments for basal-like patients using various therapeutics but failed due to the complex and dynamic nature of the disease. In this study, we performed a transcriptomic analysis of patients with breast cancer to construct a simplified but essential molecular regulatory network model. Network control analysis identified potential targets and elucidated the underlying mechanisms of reprogramming basal-like cancer cells into luminal A cells. Inhibition of BCL11A and HDAC1/2 effectively drove basal-like cells to transition to luminal A cells and increased ERα expression, leading to increased tamoxifen sensitivity. High expression of BCL11A and HDAC1/2 correlated with poor prognosis in patients with breast cancer. These findings identify mechanisms regulating breast cancer phenotypes and suggest the potential to reprogram basal-like breast cancer cells to enhance their targetability. SIGNIFICANCE: A network model enables investigation of mechanisms regulating the basal-to-luminal transition in breast cancer, identifying BCL11A and HDAC1/2 as optimal targets that can induce basal-like breast cancer reprogramming and endocrine therapy sensitivity.

Targeting eIF4F translation complex sensitizes B-ALL cells to tyrosine kinase inhibition.

The mechanistic target of rapamycin (mTOR) is a kinase whose activation is associated with poor prognosis in pre-B cell acute lymphoblastic leukemia (B-ALL). These and other findings have prompted diverse strategies for targeting mTOR signaling in B-ALL and other B-cell malignancies. In cellular models of Philadelphia Chromosome-positive (Ph+) B-ALL, mTOR kinase inhibitors (TOR-KIs) that inhibit both mTOR-complex-1 (mTORC1) and mTOR-complex-2 (mTORC2) enhance the cytotoxicity of tyrosine kinase inhibitors (TKIs) such as dasatinib. However, TOR-KIs have not shown substantial efficacy at tolerated doses in blood cancer clinical trials. Selective inhibition of mTORC1 or downstream effectors provides alternative strategies that may improve selectivity towards leukemia cells. Of particular interest is the eukaryotic initiation factor 4F (eIF4F) complex that mediates cap-dependent translation. Here we use novel chemical and genetic approaches to show that selective targeting of either mTORC1 kinase activity or components of the eIF4F complex sensitizes murine BCR-ABL-dependent pre-B leukemia cells to dasatinib. SBI-756, a small molecule inhibitor of eIF4F assembly, sensitizes human Ph+ and Ph-like B-ALL cells to dasatinib cytotoxicity without affecting survival of T lymphocytes or natural killer cells. These findings support the further evaluation of eIF4F-targeted molecules in combination therapies with TKIs in B-ALL and other blood cancers.

Physical activity status in relation to quality of life and dietary habits in breast cancer survivors: subset analyses of KROG 14-09 nationwide questionnaire study.

PURPOSE: We investigated the relationship of physical activity with dietary habits and quality of life (QoL) in breast cancer survivors in accordance with the recommendations of the American Cancer Society. METHODS: Data of 928 breast cancer survivors were obtained from the KROG 14-09 study to measure QoL in early phase after adjuvant radiotherapy. According to the extent of physical activity, survivors were divided into four groups: inactivity (0-149 min/week, N = 144), regular activity (150-450 min/week, N = 309), moderate activity (451-900 min/week, N = 229), and marked activity (901-1800 min/week, N = 164) excluding hyperactivity (> 1800 min/week, N = 82) as it is a difficult condition to recommend to survivors. Global physical activity questionnaire, 5-dimensional questionnaire by EuroQoL (EQ-5D-3L), QoL Questionnaire-breast cancer (QLQ-BR23) from EORTC, and dietary habits were surveyed. A linear-to-linear association test for EQ-5D-3L and Kruskal-Wallis analysis for QLQ-BR23 and dietary habit were conducted. RESULTS: Overall, 15.5% respondents (144/928) were classified as physically inactive. The trends of frequent intake of fruits (p = 0.001) and vegetable (p = 0.005) and reluctance toward fatty food (p < 0.001) were observed in physically active groups. Mobility (p = 0.021) and anxiety (p = 0.030) of EQ-5D-3L, and systemic therapy side effect (p = 0.027) and future perspective (p = 0.008) of QLQ-BR23 were better in physically active groups besides body image (p = 0.003) for the survivors with breast-conserving surgery. However, moderate and marked activities did not further improve QoL than regular activity. CONCLUSION: Physicians and care-givers have to pay attention to inactive survivors to boost their physical activity, thereby facilitating a better QoL and dietary habit.

Utility of PD-L1 immunocytochemistry using body-fluid cell blocks in patients with non-small-cell lung cancer.

BACKGROUND: The expression of programmed cell death ligand-1 (PD-L1) is a biomarker in patients with non-small-cell lung carcinoma (NSCLC). Patients with advanced-stage NSCLC receive a variety of molecular genetic tests, possibly resulting in insufficient tissue for immunoassay of PD-L1. Thus, to determine whether effusion fluid specimens are a reliable alternative to tissue specimens for PD-L1 testing, we compared the results of PD-L1 immunostaining using body-fluid cell blocks and tumor tissues. METHODS: PD-L1 immunostaining was performed in 62 paired samples of cytology cell blocks (ie, immunocytochemistry) and tumor tissues (ie, immunohistochemistry) from 36 patients using the E1L3N, SP142, and SP263 anti PD-L1 antibody clones. Of the 62 cytology specimens, 50 were from malignant effusion fluid. PD-L1 expression was scored as the percentage of tumor cells with clear membranous staining. RESULTS: A strong positive correlation was observed between the immunostains on cytology cell blocks and tumor tissue (Pearson's correlation coefficient, R = .804, P < .001). When the score was categorized as <1%, ≥1% and <10%, ≥10% and <50%, and ≥50%, the overall concordance rate was 74.2% (46/62, Cohen's k = 0.568). After dichotomizing the cases using cutoff values of 1%, 10%, and 50%, the concordance rates were 84% to 100% for both adenocarcinoma and squamous cell carcinoma. The concordance rate was higher in patients with NSCLC with an EGFR mutation and using the SP263 rather than the E1L3N clone. CONCLUSION: The results of PD-L1 immunostaining of cell blocks, particularly from effusion fluid, reflect the PD-L1 expression status of NSCLC tissue.

Analytical methods for determination of carbonyl compounds and nicotine in electronic No-Smoking aid refill solutions.

The present investigation aimed to develop analytical methods to determine carbonyl compounds and nicotine and to assess the carbonyl compounds and nicotine concentrations in commercial refill solutions for electronic no-smoking aids (ENSAs). The analytical methods for carbonyl compounds and nicotine in refill solutions for ENSAs were developed and analyzed from 30 popular branded products by gas chromatography and liquid chromatography. They were then validated in terms of linearity of the calibration curve, limit of detection (LOD), limit of quantification (LOQ), accuracy (%), and precision (%). Further, the existence of carbonyl compounds and nicotine in the refill solutions for ENSAs was also evaluated. None of the samples contained nicotine, but carbonyl compounds were sensed in a concentration range from 0.9 to 11.65 µg/mL. Manufacturers of ENSA refill solutions have advertised no-smoking aids as less harmful than tobacco cigarettes and as free from harmful substances. However, carbonyl compounds were detected in all 30 samples. The investigation of ENSA refill solutions needs to be broadened to gain a better accepting of the existence of harmful materials in ENSA refill solutions and prevent unsuspected ill-health effects.

Questionnaire study of the dietary habits of breast cancer survivors and their relationship to quality of life (KROG 14-09).

We evaluated the dietary habits of breast cancer survivors and investigated the relationship with quality of life (QoL), with 1,156 survivors recruited from 17 institutions. We used the Questionnaire Survey of Dietary Habits of Korean Adults (Q-DH-KOR) comprising 25 questions. The following indices were derived as follows: (1) quality of healthy dietary habits (Q-HD)-eight questions on number of meals, regularity, quantity, duration, skipping breakfast, dinner with companion(s), overeating and late-night snacks; (2) habits of nutritional balance (H-NB)-questions on consuming five food categories (grains, fruits, proteins, vegetables and dairy products); and (3) habits of unhealthy foods (H-UF)-questions on consuming three food categories (fatty, instant and fast foods). The times and regularity of meals, frequency of skipping breakfast, dinner with companion(s) and overeating were better in groups with high symptomatic and functional QoL. Symptomatic QoL positively affected Q-HD and H-NB (p < 0.001 and p = 0.024 respectively) and negatively affected H-UF (p = 0.02). Breast cancer survivors more frequently ate from the fruit, protein and vegetable categories than did the control group, with lower H-UF and higher Q-HD values (p < 0.001 and p < 0.001 respectively). Our findings supported the relationship between QoL and dietary habit and showed healthier dietary habits of breast cancer survivors than controls.

Re-exploration of U's Triangle Brassica Species Based on Chloroplast Genomes and 45S nrDNA Sequences.

The concept of U's triangle, which revealed the importance of polyploidization in plant genome evolution, described natural allopolyploidization events in Brassica using three diploids [B. rapa (A genome), B. nigra (B), and B. oleracea (C)] and derived allotetraploids [B. juncea (AB genome), B. napus (AC), and B. carinata (BC)]. However, comprehensive understanding of Brassica genome evolution has not been fully achieved. Here, we performed low-coverage (2-6×) whole-genome sequencing of 28 accessions of Brassica as well as of Raphanus sativus [R genome] to explore the evolution of six Brassica species based on chloroplast genome and ribosomal DNA variations. Our phylogenomic analyses led to two main conclusions. (1) Intra-species-level chloroplast genome variations are low in the three allotetraploids (2~7 SNPs), but rich and variable in each diploid species (7~193 SNPs). (2) Three allotetraploids maintain two 45SnrDNA types derived from both ancestral species with maternal dominance. Furthermore, this study sheds light on the maternal origin of the AC chloroplast genome. Overall, this study clarifies the genetic relationships of U's triangle species based on a comprehensive genomics approach and provides important genomic resources for correlative and evolutionary studies.

Lentibacillus alimentarius sp. nov., isolated from Myeolchi-jeotgal, a traditional Korean high-salt fermented anchovy.

A Gram-positive, motile, endospore-forming, rod-shaped bacterium, designated strain M2024T, was isolated from Myeolchi-jeotgal, a traditional Korean high-salt fermented anchovy and was characterised using a polyphasic taxonomic approach. Comparative 16S rRNA gene sequence analysis showed that strain M2024T belongs to the genus Lentibacillus in the family Bacillaceae of the Firmicutes. The 16S rRNA gene sequence analysis showed that strain M2024T is closely related to Lentibacillus populi WD4L-1T (95.5%), Lentibacillus garicola SL-MJ1T (95.2%) and Virgibacillus siamensis MS3-4T (95.1%). The chemotaxonomic properties of strain M2024T are consistent with those of members of the genus Lentibacillus: the quinone system has MK-7 as the predominant menaquinone and anteiso-C15:0 and anteiso-C17:0 are the predominant cellular fatty acids. The major polar lipids were identified as diphosphatidylglycerol, phosphatidylglycerol and phosphatidylethanolamine. The G+C content of the genomic DNA was determined to be 36.2 mol%. Differential phenotypic properties compared with closely related type strains support the conclusion that strain M2024T can be separated from previously described members of the genus Lentibacillus. The strain thus represents a novel species in this genus, for which the name Lentibacillus alimentarius sp. nov. is proposed. The type strain is M2024T (= KEMB 9001-124T = JCM 16521T).

Percolation transition of cooperative mutational effects in colorectal tumorigenesis.

Cancer is caused by the accumulation of multiple genetic mutations, but their cooperative effects are poorly understood. Using a genome-wide analysis of all the somatic mutations in colorectal cancer patients in a large-scale molecular interaction network, here we find that a giant cluster of mutation-propagating modules in the network undergoes a percolation transition, a sudden critical transition from scattered small modules to a large connected cluster, during colorectal tumorigenesis. Such a large cluster ultimately results in a giant percolated cluster, which is accompanied by phenotypic changes corresponding to cancer hallmarks. Moreover, we find that the most commonly observed sequence of driver mutations in colorectal cancer has been optimized to maximize the giant percolated cluster. Our network-level percolation study shows that the cooperative effect rather than any single dominance of multiple somatic mutations is crucial in colorectal tumorigenesis.

Genomic insights into the virulence and salt tolerance of Staphylococcus equorum.

To shed light on the genetic background behind the virulence and salt tolerance of Staphylococcus equorum, we performed comparative genome analysis of six S. equorum strains. Data on four previously published genome sequences were obtained from the NCBI database, while those on strain KM1031 displaying resistance to multiple antibiotics and strain C2014 causing haemolysis were determined in this study. Examination of the pan-genome of five of the six S. equorum strains showed that the conserved core genome retained the genes for general physiological processes and survival of the species. In this comparative genomic analysis, the factors that distinguish the strains from each other, including acquired genomic factors in mobile elements, were identified. Additionally, the high salt tolerance of strains enabling growth at a NaCl concentration of 25% (w/v) was attributed to the genes encoding potassium voltage-gated channels. Among the six strains, KS1039 does not possess any of the functional virulence determinants expressed in the other strains.