Conditional random pattern model for copy number aberration detection

<p>Abstract</p> <p>Background</p> <p>DNA copy number aberration (CNA) is very important in the pathogenesis of tumors and other diseases. For example, CNAs may result in suppression of anti-oncogenes and activation of oncogenes, which would cause certain types of cancers. High density single nucleotide polymorphism (SNP) array data is widely used for the CNA detection. However, it is nontrivial to detect the CNA automatically because the signals obtained from high density SNP arrays often have low signal-to-noise ratio (SNR), which might be caused by whole genome amplification, mixtures of normal and tumor cells, experimental noise or other technical limitations. With the reduction in SNR, many false CNA regions are often detected and the true CNA regions are missed. Thus, more sophisticated statistical models are needed to make the CNAs detection, using the low SNR signals, more robust and reliable.</p> <p>Results</p> <p>This paper presents a conditional random pattern (CRP) model for CNA detection where much contextual cues are explored to suppress the noise and improve CNA detection accuracy. Both simulated and the real data are used to evaluate the proposed model, and the validation results show that the CRP model is more robust and reliable in the presence of noise for CNA detection using high density SNP array data, compared to a number of widely used software packages.</p> <p>Conclusions</p> <p>The proposed conditional random pattern (CRP) model could effectively detect the CNA regions in the presence of noise.</p

Nanoscale integrin cluster dynamics controls cellular mechanosensing via FAKY397 phosphorylation

Transduction of extracellular matrix mechanics affects cell migration, proliferation, and differentiation. While this mechanotransduction is known to depend on the regulation of focal adhesion kinase phosphorylation on Y397 (FAKpY397), the mechanism remains elusive. To address this, we developed a mathematical model to test the hypothesis that FAKpY397-based mechanosensing arises from the dynamics of nanoscale integrin clustering, stiffness-dependent disassembly of integrin clusters, and FAKY397 phosphorylation within integrin clusters. Modeling results predicted that integrin clustering dynamics governs how cells convert substrate stiffness to FAKpY397, and hence governs how different cell types transduce mechanical signals. Existing experiments on MDCK cells and HT1080 cells, as well as our new experiments on 3T3 fibroblasts, confirmed our predictions and supported our model. Our results suggest a new pathway by which integrin clusters enable cells to calibrate responses to their mechanical microenvironment

Security and usability of a personalized user authentication paradigm : insights from a longitudinal study with three healthcare organizations

Funding information: This research has been partially supported by the EU Horizon 2020 Grant 826278 "Securing Medical Data in Smart Patient-Centric Healthcare Systems" (Serums) , and the Research and Innovation Foundation (Project DiversePass: COMPLEMENTARY/0916/0182).This paper proposes a user-adaptable and personalized authentication paradigm for healthcare organizations, which anticipates to seamlessly reflect patients’ episodic and autobiographical memories to graphical and textual passwords aiming to improve the security strength of user-selected passwords and provide a positive user experience. We report on a longitudinal study that spanned over three years in which three public European healthcare organizations participated in order to design and evaluate the aforementioned paradigm. Three studies were conducted (n=169) with different stakeholders: i) a verification study aiming to identify existing authentication practices of the three healthcare organizations with diverse stakeholders (n=9); ii) a patient-centric feasibility study during which users interacted with the proposed authentication system (n=68); and iii) a human guessing attack study focusing on vulnerabilities among people sharing common experiences within location-aware images used for graphical passwords (n=92). Results revealed that the suggested paradigm scored high with regards to users’ likeability, perceived security, usability and trust, but more importantly it assists the creation of more secure passwords. On the downside, the suggested paradigm introduces password guessing vulnerabilities by individuals sharing common experiences with the end-users. Findings are expected to scaffold the design of more patient-centric knowledge-based authentication mechanisms within nowadays dynamic computation realms.PostprintPeer reviewe

Altered cortical thickness-based structural covariance networks in type 2 diabetes mellitus

Cognitive impairment is a common complication of type 2 diabetes mellitus (T2DM), and early cognitive dysfunction may be associated with abnormal changes in the cerebral cortex. This retrospective study aimed to investigate the cortical thickness-based structural topological network changes in T2DM patients without mild cognitive impairment (MCI). Fifty-six T2DM patients and 59 healthy controls underwent neuropsychological assessments and sagittal 3-dimensional T1-weighted structural magnetic resonance imaging. Then, we combined cortical thickness-based assessments with graph theoretical analysis to explore the abnormalities in structural covariance networks in T2DM patients. Correlation analyses were performed to investigate the relationship between the altered topological parameters and cognitive/clinical variables. T2DM patients exhibited significantly lower clustering coefficient (C) and local efficiency (Elocal) values and showed nodal property disorders in the occipital cortical, inferior temporal, and inferior frontal regions, the precuneus, and the precentral and insular gyri. Moreover, the structural topological network changes in multiple nodes were correlated with the findings of neuropsychological tests in T2DM patients. Thus, while T2DM patients without MCI showed a relatively normal global network, the local topological organization of the structural network was disordered. Moreover, the impaired ventral visual pathway may be involved in the neural mechanism of visual cognitive impairment in T2DM patients. This study enriched the characteristics of gray matter structure changes in early cognitive dysfunction in T2DM patients

The impact of parental overprotection on the emotions and behaviors of pediatric hematologic cancer patients: a multicenter cross-sectional study

BackgroundParental overprotection may have an impact on children’s emotional and behavioral problems (EBPs). As pediatric hematologic cancer patients have compromised immune systems, parents of such children often worry excessively, interfering with their daily lives. Therefore, avoiding overprotection is crucial for the overall physical and mental health of pediatric hematologic cancer patients.AimsThe aim of this study was to examine the current status of EBPs in pediatric hematologic cancer patients and analyze their associated risk factors.DesignThis work was a multicenter cross-sectional observational and correlational study. We collected data anonymously through parental questionnaires from three pediatric hematologic oncology hospitals in China. The Strengths and Difficulties Questionnaire, the Parental Overprotection Measure (POM) scale, and a general information survey designed by the research team were employed to assess children’s EBPs, the degree of parental overprotection, as well as basic demographic and disease-related information. Chi-square tests and generalized linear mixed-effects regression analysis were used to analyze the factors influencing EBPs among the pediatric hematologic cancer patients.Setting and participantsUsing a convenience sampling method, a total of 202 participants’ parents were selected. All participants were invited to complete the questionnaire through one-on-one guidance.ResultsEmotional symptoms accounted for the highest proportion of abnormal EBPs in children (27.72%), followed by peer problems (26.24%), prosocial behavior (25.74%), behavioral problems (14.36%), and total difficulties (13.86%). A minority of children had abnormal hyperactivity scores (4.95%). The results of a generalized linear mixed regression analysis showed that age, duration of illness, and parental overprotection were significant factors influencing abnormal EBPs in children (p &lt; 0.05). A POM score threshold of 37 exhibited good sensitivity (74%) and specificity (90%) in predicting abnormal EBPs in children.ConclusionPediatric hematologic cancer patients under excessive parental protection are more prone to experiencing EBPs. Healthcare professionals should guide parents to reduce this excessive protection, thus mitigating the occurrence of EBPs in children

Template bank for compact binary mergers in the fourth observing run of Advanced LIGO, Advanced Virgo, and KAGRA

Template banks containing gravitational wave (GW) waveforms are essential for matched-filtering GW search pipelines. We describe the generation method, the design, and validation of the template bank used by the GstLAL-based inspiral pipeline to analyze data from the fourth observing run of LIGO scientific, Virgo, and KAGRA collaboration. This paper presents a template bank containing $1.8 \times 10^6$ templates that include merging neutron star - neutron star, neutron star - black hole, and black hole - black hole systems up to a total mass of $400$ $M_\odot$. Motivated by observations, component masses below $3$ $M_\odot$ have dimensionless spins ranging between $\pm 0.05$, while component masses between $3$ to $200$ $M_\odot$ have dimensionless spins ranging between $\pm 0.99$, where we assume spin-aligned systems. The low-frequency cutoff is $15$ Hz. The templates are placed in the parameter space according to the metric via a binary tree approach which took $\mathcal{O}\left(10\right)$ minutes when jobs were parallelized. The template bank generated with this method has a $98\%$ match or higher for $90\%$ of the injections, thus being as effective as the template placement method used for the previous observation runs. The volumes of the templates are computed prior to template placement and the nearby templates have similar volumes in the coordinate space, henceforth, enabling a more efficient and less biased implementation of population models. SVD sorting of the O4 template bank has been renewed to use post-Newtonian phase terms, which improved the computational efficiency of SVD by nearly $4 \sim 5$ times as compared to conventional SVD sorting schemes. Template banks and searches focusing on the sub-solar mass parameter space and intermediate-mass black hole parameter space are conducted separately

When to Point Your Telescopes: Gravitational Wave Trigger Classification for Real-Time Multi-Messenger Followup Observations

We develop a robust and self-consistent framework to extract and classify gravitational wave candidates from noisy data, for the purpose of assisting in real-time multi-messenger follow-ups during LIGO-Virgo-KAGRA's fourth observing run~(O4). Our formalism implements several improvements to the low latency calculation of the probability of astrophysical origin~(\PASTRO{}), so as to correctly account for various factors such as the sensitivity change between observing runs, and the deviation of the recovered template waveform from the true gravitational wave signal that can strongly bias said calculation. We demonstrate the high accuracy with which our new formalism recovers and classifies gravitational wave triggers, by analyzing replay data from previous observing runs injected with simulated sources of different categories. We show that these improvements enable the correct identification of the majority of simulated sources, many of which would have otherwise been misclassified. We carry out the aforementioned analysis by implementing our formalism through the \GSTLAL{} search pipeline even though it can be used in conjunction with potentially any matched filtering pipeline. Armed with robust and self-consistent \PASTRO{} values, the \GSTLAL{} pipeline can be expected to provide accurate source classification information for assisting in multi-messenger follow-up observations to gravitational wave alerts sent out during O4.Comment: v2 upload was accidental. revert back to v

Performance of the low-latency GstLAL inspiral search towards LIGO, Virgo, and KAGRA's fourth observing run

GstLAL is a stream-based matched-filtering search pipeline aiming at the prompt discovery of gravitational waves from compact binary coalescences such as the mergers of black holes and neutron stars. Over the past three observation runs by the LIGO, Virgo, and KAGRA (LVK) collaboration, the GstLAL search pipeline has participated in several tens of gravitational wave discoveries. The fourth observing run (O4) is set to begin in May 2023 and is expected to see the discovery of many new and interesting gravitational wave signals which will inform our understanding of astrophysics and cosmology. We describe the current configuration of the GstLAL low-latency search and show its readiness for the upcoming observation run by presenting its performance on a mock data challenge. The mock data challenge includes 40 days of LIGO Hanford, LIGO Livingston, and Virgo strain data along with an injection campaign in order to fully characterize the performance of the search. We find an improved performance in terms of detection rate and significance estimation as compared to that observed in the O3 online analysis. The improvements are attributed to several incremental advances in the likelihood ratio ranking statistic computation and the method of background estimation.Comment: 19 pages, 21 figure

Association analyses of East Asian individuals and trans-ancestry analyses with European individuals reveal new loci associated with cholesterol and triglyceride levels

Large-scale meta-analyses of genome-wide association studies (GWAS) have identified >175 loci associated with fasting cholesterol levels, including total cholesterol (TC), high-density lipoprotein cholesterol (HDL-C), low-density lipoprotein cholesterol (LDL-C), and triglycerides (TG). With differences in linkage disequilibrium (LD) structure and allele frequencies between ancestry groups, studies in additional large samples may detect new associations. We conducted staged GWAS meta-analyses in up to 69,414 East Asian individuals from 24 studies with participants from Japan, the Philippines, Korea, China, Singapore, and Taiwan. These meta-analyses identified (P < 5 × 10-8) three novel loci associated with HDL-C near CD163-APOBEC1 (P = 7.4 × 10-9), NCOA2 (P = 1.6 × 10-8), and NID2-PTGDR (P = 4.2 × 10-8), and one novel locus associated with TG near WDR11-FGFR2 (P = 2.7 × 10-10). Conditional analyses identified a second signal near CD163-APOBEC1. We then combined results from the East Asian meta-analysis with association results from up to 187,365 European individuals from the Global Lipids Genetics Consortium in a trans-ancestry meta-analysis. This analysis identified (log10Bayes Factor ≥6.1) eight additional novel lipid loci. Among the twelve total loci identified, the index variants at eight loci have demonstrated at least nominal significance with other metabolic traits in prior studies, and two loci exhibited coincident eQTLs (P < 1 × 10-5) in subcutaneous adipose tissue for BPTF and PDGFC. Taken together, these analyses identified multiple novel lipid loci, providing new potential therapeutic targets