Transcriptome Analysis of Systems Biology for Schizophrenia

Transcriptome analysis of postmortem brain samples provides more insights to evaluate biological dysfunctions by analysis of differential expression and genetic interactions in schizophrenia. The growing development of new technologies such as next-generation sequencing (NGS) helps to explore detailed and underlying molecular changes from global perspective of view, not only focus in single SNP variants. It is implicated that schizophrenia genetic and protein interactions may give rise to biological dysfunction not only in dopamine dysfunction but also in immune, energy metabolism, mitochondrial dysfunction and hemostasis. Epigenetic investigation of schizophrenia provides important information on how the environmental factors affect the genetic architecture of the disease. DNA methylation plays a pivotal role in etiology for schizophrenia. The schizophrenia differential methylation genes and differential expression genes were analyzed to find the potential protein complexes related to the etiology of schizophrenia from alteration of DNA methylation. The protein complexes and pathways involved in schizophrenia differential methylation network may be responsible for the etiology and potential treatment targets. It is implicated that the interaction between differential expression candidate genes and differential methylation genes may describe the global view of disease mechanisms and it has important roles in the pathogenesis for schizophrenia

Reanalyze unassigned reads in Sanger based metagenomic data using conserved gene adjacency

<p>Abstract</p> <p>Background</p> <p>Investigation of metagenomes provides greater insight into uncultured microbial communities. The improvement in sequencing technology, which yields a large amount of sequence data, has led to major breakthroughs in the field. However, at present, taxonomic binning tools for metagenomes discard 30-40% of Sanger sequencing data due to the stringency of BLAST cut-offs. In an attempt to provide a comprehensive overview of metagenomic data, we re-analyzed the discarded metagenomes by using less stringent cut-offs. Additionally, we introduced a new criterion, namely, the evolutionary conservation of adjacency between neighboring genes. To evaluate the feasibility of our approach, we re-analyzed discarded contigs and singletons from several environments with different levels of complexity. We also compared the consistency between our taxonomic binning and those reported in the original studies.</p> <p>Results</p> <p>Among the discarded data, we found that 23.7 ± 3.9% of singletons and 14.1 ± 1.0% of contigs were assigned to taxa. The recovery rates for singletons were higher than those for contigs. The <it>Pearson </it>correlation coefficient revealed a high degree of similarity (0.94 ± 0.03 at the phylum rank and 0.80 ± 0.11 at the family rank) between the proposed taxonomic binning approach and those reported in original studies. In addition, an evaluation using simulated data demonstrated the reliability of the proposed approach.</p> <p>Conclusions</p> <p>Our findings suggest that taking account of conserved neighboring gene adjacency improves taxonomic assignment when analyzing metagenomes using Sanger sequencing. In other words, utilizing the conserved gene order as a criterion will reduce the amount of data discarded when analyzing metagenomes.</p

A quantitative analysis of monochromaticity in genetic interaction networks

<p>Abstract</p> <p>Background</p> <p>A genetic interaction refers to the deviation of phenotypes from the expected when perturbing two genes simultaneously. Studying genetic interactions help clarify relationships between genes, such as compensation and masking, and identify gene groups of functional modules. Recently, several genome-scale experiments for measuring quantitative (positive and negative) genetic interactions have been conducted. The results revealed that genes in the same module usually interact with each other in a consistent way (pure positive or negative); this phenomenon was designated as monochromaticity. Monochromaticity might be the underlying principle that can be utilized to unveil the modularity of cellular networks. However, no appropriate quantitative measurement for this phenomenon has been proposed.</p> <p>Results</p> <p>In this study, we propose the monochromatic index (MCI), which is able to quantitatively evaluate the monochromaticity of potential functional modules of genes, and the MCI was used to study genetic landscapes in different cellular subsystems. We demonstrated that MCI not only amend the deficiencies of MP-score but also properly incorporate the background effect. The results showed that not only within-complex but also between-complex connections present significant monochromatic tendency. Furthermore, we also found that significantly higher proportion of protein complexes are connected by negative genetic interactions in metabolic network, while transcription and translation system adopts relatively even number of positive and negative genetic interactions to link protein complexes.</p> <p>Conclusion</p> <p>In summary, we demonstrate that MCI improves deficiencies suffered by MP-score, and can be used to evaluate monochromaticity in a quantitative manner. In addition, it also helps to unveil features of genetic landscapes in different cellular subsystems. Moreover, MCI can be easily applied to data produced by different types of genetic interaction methodologies such as Synthetic Genetic Array (SGA), and epistatic miniarray profile (E-MAP).</p

CTX-M and Plasmid-mediated AmpC-Producing Enterobacteriaceae, Singapore

10.3201/eid1006.030726Emerging Infectious Diseases1061172-117

Gab2 Promotes Hematopoietic Stem Cell Maintenance and Self-Renewal Synergistically with STAT5

Grb2-associated binding (Gab) adapter proteins play major roles in coordinating signaling downstream of hematopoietic cytokine receptors. In hematopoietic cells, Gab2 can modulate phosphatidylinositol–3 kinase and mitogen associated protein kinase activities and regulate the long-term multilineage competitive repopulating activity of hematopoietic stem cells (HSCs). Gab2 may also act in a linear pathway upstream or downstream of signal transducer and activator of transcription-5 (STAT5), a major positive regulator of HSC function. Therefore, we aimed to determine whether Gab2 and STAT5 function in hematopoiesis in a redundant or non-redundant manner.), reduced HSC survival, and dramatic loss of self-renewal potential as measured by serial transplantation.These data demonstrate new functions for Gab2 in hematopoiesis in a manner that is non-redundant with STAT5. Furthermore, important synergy between STAT5 and Gab2 was observed in HSC self-renewal, which might be exploited to optimize stem cell-based therapeutics

Self-supervised learning-based general laboratory progress pretrained model for cardiovascular event detection

The inherent nature of patient data poses several challenges. Prevalent cases amass substantial longitudinal data owing to their patient volume and consistent follow-ups, however, longitudinal laboratory data are renowned for their irregularity, temporality, absenteeism, and sparsity; In contrast, recruitment for rare or specific cases is often constrained due to their limited patient size and episodic observations. This study employed self-supervised learning (SSL) to pretrain a generalized laboratory progress (GLP) model that captures the overall progression of six common laboratory markers in prevalent cardiovascular cases, with the intention of transferring this knowledge to aid in the detection of specific cardiovascular event. GLP implemented a two-stage training approach, leveraging the information embedded within interpolated data and amplify the performance of SSL. After GLP pretraining, it is transferred for TVR detection. The proposed two-stage training improved the performance of pure SSL, and the transferability of GLP exhibited distinctiveness. After GLP processing, the classification exhibited a notable enhancement, with averaged accuracy rising from 0.63 to 0.90. All evaluated metrics demonstrated substantial superiority (p < 0.01) compared to prior GLP processing. Our study effectively engages in translational engineering by transferring patient progression of cardiovascular laboratory parameters from one patient group to another, transcending the limitations of data availability. The transferability of disease progression optimized the strategies of examinations and treatments, and improves patient prognosis while using commonly available laboratory parameters. The potential for expanding this approach to encompass other diseases holds great promise.Comment: published in IEEE Journal of Translational Engineering in Health & Medicin

Association between leucocyte telomere length and the risk of atrial fibrillation: An updated systematic review and meta-analysis

Advancing age is the most important risk factor of atrial fibrillation (AF). The shortening of telomere length is a biomarker of biologic aging. There is an increasing body of evidence that leucocyte telomere length (LTL) is associated with the risk of AF development. However, the results in these studies were controversial. The current systematic review and meta-analysis was conducted to examine the role of LTL in predicting the incidence of AF. Observational studies reporting the association between LTL and the risk of AF were retrieved through 25th June, 2022 from PubMed and Embase. A total of twelve studies including 18,293 patients were included in the present analysis. Leucocyte telomere shortening was found to be an independent predictor of AF as a continuous variable in both univariate [OR:2.14; 95%CI(1.48,3.10); P < 0.0001] and multivariate analyses [OR:1.41;95%CI(1.11,1.79); P = 0.005], as well as categorical variable in multivariate analysis [OR:1.53; 95%CI(1.04,2.27); P = 0.03]. Furthermore, leucocyte telomere shortening was significantly associated with recurrent AF [OR:4.32;95%CI(2.42,7.69); P < 0.00001] but not new-onset AF [OR:1.14; 95%CI(0.90,1.45); P = 0.29]. Leucocyte telomere shortening was also associated with an increased risk of persistent AF [OR:14.73;95%CI (3.16,68.67); P = 0.0006] and paroxysmal AF [OR:2.74;95%CI(1.45,5.18); P = 0.002]. Besides, LTL was an independent predictor for progression from paroxysmal AF to persistent AF [OR:3.2;95%CI(1.66,6.18); P = 0.0005]. Differences between males [OR:1.99; 95%CI(1.29,3.06); P = 0.002] and females [OR:0.86; 95%CI (0.29,2.56);P = 0.79] were observed. Leucocyte telomere shortening predicts the risk of AF, especially recurrent AF. The predictive value is more prominent in males than in females. Shortening in LTL can predict the progression from paroxysmal to persistent AF

Electrocardiographic characteristics of bladder cancer patients receiving preoperative chemotherapy combined with immunotherapy.

Objective Patients treated with preoperative chemotherapy and immunotherapy for bladder cancer may be at increased risk of cardiotoxicity and electrophysiological abnormalities. This study aimed to analyze their electrocardiographic (ECG) alterations. Methods Patients with bladder cancer who were hospitalized and receiving tislelizumab plus nab-paclitaxel (TnP) were enrolled prospectively. ECG, cardiac biomarkers, and echocardiography were performed at baseline and the end of TnP. Results A total of 60 patients (76.7% males), including 30 muscle-invasive and 30 non-muscle-invasive bladder cancer, received three or four cycles of TnP, respectively. Hypertension was the commonest comorbidity (41.7%), and 25 patients (41.7%) were prescribed cardiovascular drugs. In comparison with baseline characteristics, cardiac troponin I (cTnI) and N-terminal pro-brain natriuretic peptide (NT-proBNP) were within normal ranges after TnP. However, echocardiographic parameter of left ventricular ejection fraction slightly decreased after TnP (62.81 ± 3.81% to 61.10 ± 4.37%, p = .011). The incidence of abnormal ECG increased from 65.0% at baseline to 76.7%, of which only a higher prevalence of fragmented QRS (fQRS) was observed (33.3% to 50.0%, p = .013; mainly in inferior leads). ECG parameters of QT dispersion (QTd) were prolonged significantly after the regimen (39.50 ± 11.37 to 44.20 ± 15.85 ms, p = .019). Conclusion In bladder cancer patients receiving preoperative chemotherapy combined with immunotherapy, the main ECG abnormality was fQRS and QTd, with relatively normal cardiac biomarkers and echocardiographic parameters. Regular ECG screening should be carried out carefully to detect potential cardiotoxicity in the long-term follow-up