Tag: statistics

Methods Mol Biol. 2023;2690:335-354. doi: 10.1007/978-1-0716-3327-4_27.

ABSTRACT

Proteins are rapidly and dynamically post-transcriptionally modified as cells respond to changes in their environment. For example, protein phosphorylation is mediated by kinases while dephosphorylation is mediated by phosphatases. Quantifying and predicting interactions between kinases, phosphatases, and target proteins over time will aid the study of signaling cascades under a variety of environmental conditions. Here, we describe methods to statistically analyze label-free phosphoproteomic data and infer posttranscriptional regulatory networks over time. We provide an R-based method that can be used to normalize and analyze label-free phosphoproteomic data using variance stabilizing normalization and a linear mixed model across multiple time points and conditions. We also provide a method to infer regulator-target interactions over time using a discretization scheme followed by dynamic Bayesian modeling computations to validate our conclusions. Overall, this pipeline is designed to perform functional analyses and predictions of phosphoproteomic signaling cascades.

PMID:37450158 | DOI:10.1007/978-1-0716-3327-4_27

Methods Mol Biol. 2023;2690:299-310. doi: 10.1007/978-1-0716-3327-4_25.

ABSTRACT

Affinity purification coupled to mass spectrometry (AP-MS) is a powerful method to analyze protein-protein interactions (PPIs). The AP-MS approach provides an unbiased analysis of the entire protein complex and is useful to identify indirect interactors. However, reliable protein identification from the complex AP-MS experiments requires appropriate control of false identifications and rigorous statistical analysis. Another challenge that can arise from AP-MS analysis is to distinguish bona fide interacting proteins from the non-specifically bound endogenous proteins or the “background contaminants” that co-purified by the bait experiments. In this chapter, we will first describe the protocol for performing in-solution trypsinization for the samples from the AP experiment followed by LC-MS/MS analysis. We will then detail the MaxQuant workflow for protein identification and quantification for the PPI data derived from the AP-MS experiment. Finally, we describe the CRAPome interface to process the data by filtering against contaminant lists, score the interactions and visualize the protein interaction networks.

PMID:37450156 | DOI:10.1007/978-1-0716-3327-4_25

Methods Mol Biol. 2023;2690:179-192. doi: 10.1007/978-1-0716-3327-4_17.

ABSTRACT

Proteins are the building blocks of life, and a vast array of cellular processes is handled by protein-protein interactions (PPIs). The protein complexes formed via PPIs lead to tangled networks that, with their continuous remodeling, build up systematic functional units. Over the years, PPIs have become an area of interest for many researchers, leading to the development of multiple in vitro and in vivo methods to reveal these interactions. The yeast-two-hybrid (Y2H) system is a potent genetic way to map PPIs in both a micro- and high-throughput manner. Y2H is a technique that involves using modified yeast cells to identify protein-protein interactions. For Y2H, the yeast cells are engineered only to grow when there is a significant interaction between a specific protein with its interacting partner. PPIs are identified in the Y2H system by stimulating reporter genes in response to a restored transcription factor. However, Y2H results may be constrained by stringency requirements, as the limited number of colony screenings through this technique could result in the possible elimination of numerous genuine interactions. Therefore, DEEPN (dynamic enrichment for evaluation of protein networks) can be used, offering the potential to study the multiple static and transient protein interactions in a single Y2H experiment. DEEPN utilizes next-generation DNA sequencing (NGS) data in a high-throughput manner and subsequently applies computational analysis and statistical modeling to identify interacting partners. This protocol describes customized reagents and protocols through which DEEPN analysis can be utilized efficiently and cost-effectively.

PMID:37450148 | DOI:10.1007/978-1-0716-3327-4_17

Carbon Balance Manag. 2023 Jul 14;18(1):13. doi: 10.1186/s13021-023-00232-2.

ABSTRACT

BACKGROUND: Understanding temporal trends and varying responses of water use efficiency (WUE) to environmental changes of diverse ecosystems is key to predicting vegetation growth. WUE dynamics of major ecosystem types (e.g., forest, grassland and cropland) have been studied using various WUE definitions/metrics, but a comparative study on WUE dynamics and their driving forces among different ecosystem types using multiple WUE metrics is lacking. We used eddy covariance measurements for 42 FLUXNET2015 sites (396 site years) from 1997 to 2014, as well as three commonly used WUE metrics (i.e., ecosystem, inherent, and underlying WUE) to investigate the commonalities and differences in WUE trends and driving factors among deciduous broadleaf forests (DBFs), evergreen needleleaf forests (ENFs), grasslands, and croplands.

RESULTS: Our results showed that the temporal trends of WUE were not statistically significant at 73.8% of the forest, grassland and cropland sites, and none of the three WUE metrics exhibited better performance than the others in quantifying WUE. Meanwhile, the trends observed for the three WUE metrics were not significantly different among forest, grassland and cropland ecosystems. In addition, WUE was mainly driven by atmospheric carbon dioxide concentration at sites with significant WUE trends, and by vapor pressure deficit (VPD) at sites without significant trends (except cropland).

CONCLUSIONS: Our findings revealed the commonalities and differences in the application of three WUE metrics in disparate ecosystems, and further highlighted the important effect of VPD on WUE change.

PMID:37450075 | DOI:10.1186/s13021-023-00232-2

Langenbecks Arch Surg. 2023 Jul 14;408(1):277. doi: 10.1007/s00423-023-03006-z.

ABSTRACT

PURPOSE: Sexual dysfunction after inguinal hernia complication is considered rare. However, its consequences impact on quality of life inevitably. Laparoscopic and open inguinal hernia repair may be comparable in terms of recurrent rate, overall complications, and chronic pain. Therefore, its complication is still questionable between these approaches. In this study, we compared sexual dysfunction and related complications between laparoscopic and open inguinal hernia repair.

METHODS: Systematic review and meta-analysis of randomized controlled trials (RCTs) studies were performed to compare laparoscopic and open inguinal hernia repair. Risk ratio (RR) and 95% confidence intervals (95% CI) were used as pooled effect size measures.

RESULT: Thirty RCTs (12,022 patients) were included. Overall, 6014 (50.02%) underwent laparoscopic hernia repair, and 6008 (49.98%) underwent open hernia repair. Laparoscopic approach provided non-significance benefit on pain during sexual activity (RR 0.57; 95% CI 0.18, 1.76), Vas deferens injury (RR 0.46; 95% CI 0.13, 1.63), orchitis (RR 0.84; CI 0.61,1.17), scrotal hematoma (RR 0.99; CI 0.62,1.60), and testicular atrophy (RR 0.46; CI 0.17,1.20). Meanwhile, the open inguinal hernia approach seems to perform better for cord seroma complications and testicular pain.

CONCLUSION: There is no advantage of laparoscopic inguinal hernia repair over an open approach concerning sexual dysfunction. On the contrary, there is an increasing risk of cord seroma after laparoscopic inguinal hernia repair with statistical significance.

PMID:37450061 | DOI:10.1007/s00423-023-03006-z

Int Immunopharmacol. 2023 Jul 11;122:110596. doi: 10.1016/j.intimp.2023.110596. Online ahead of print.

ABSTRACT

Corona Virus Disease 2019 (COVID-19) is an acute respiratory infection and a global public health event. The level of aβ₂GPI is significantly up-regulated in COVID-19 patients. The impact of inactivated vaccination against COVID-19 on aβ₂GPI and in vitro fertilization and embryo transfer (IVF-ET) remains unknown amidst the universal administration of COVID-19 vaccines. We conducted a retrospective study to assess the impact of COVID-19 inactivated vaccination on aβ₂GPI levels and its effect on superovulation and pregnancy outcomes. We found aβ₂GPI level is significantly up-regulated after vaccination. There was no statistical difference in mature egg rate, 2PN fertilization rate, day 3 high-quality embryo rate, blastocyst formation rate, embryo implantation rate and miscarriage rate between the vaccine group and control group. Our findings showed vaccination with COVID-19 inactivated vaccine can elevate the level of aβ₂GPI in peripheral blood but have no effect on the outcomes of controlled ovarian hyperstimulation and pregnancy in IVF-ET.

PMID:37441812 | DOI:10.1016/j.intimp.2023.110596

Death Stud. 2023 Jul 13:1-10. doi: 10.1080/07481187.2023.2231388. Online ahead of print.

ABSTRACT

The purpose of this study was to (1) explore associations between preparedness for caregiving and preparedness for death among family caregivers of patients with advanced cancer and (2) explore modifiable preparedness factors, such as communication and support. Data was derived from a baseline questionnaire collected in specialized home care. The questionnaire included socio-demographics, the Preparedness for Caregiving Scale, and single items addressing preparedness for death, received support and communication about incurable illness. Data was analyzed using descriptive statistics and Spearman correlations. Altogether 39 family caregivers participated. A significant association was found between preparedness for caregiving and preparedness for death. Received support and communication about the illness was associated with higher levels of preparedness for caregiving and death. This study contributes to evidence on the association between preparedness for caregiving and death, but also that communication and support employed by healthcare professionals could improve family caregiver preparedness and wellbeing.

PMID:37441803 | DOI:10.1080/07481187.2023.2231388

Obstet Gynecol. 2023 Jul 13. doi: 10.1097/AOG.0000000000005310. Online ahead of print.

ABSTRACT

OBJECTIVE: To assess the association between coronavirus disease 2019 (COVID-19) vaccination and female assisted reproduction outcomes through a systematic review and meta-analysis.

DATA SOURCES: We searched Medline (OVID), EMBASE, Web of Science, Cochrane Library, and ClinicalTrials.gov on January 11, 2023, for original articles on assisted reproduction outcomes after COVID-19 vaccination. The primary outcome was rates of clinical pregnancy; secondary outcomes included number of oocytes retrieved, number of mature oocytes retrieved, fertilization rate, implantation rate, ongoing pregnancy rate, and live-birth rate.

METHODS OF STUDY SELECTION: Two reviewers independently screened citations for relevance, extracted pertinent data, and rated study quality. Only peer-reviewed published studies were included.

TABULATION, INTEGRATION, AND RESULTS: Our query retrieved 216 citations, of which 25 were studies with original, relevant data. Nineteen studies reported embryo transfer outcomes, with a total of 4,899 vaccinated and 13,491 unvaccinated patients. Eighteen studies reported data on ovarian stimulation outcomes, with a total of 1,878 vaccinated and 3,174 unvaccinated patients. There were no statistically significant results among our pooled data for any of the primary or secondary outcomes: clinical pregnancy rate (odds ratio [OR] 0.94, 95% CI 0.88-1.01, P=.10), number of oocytes retrieved (mean difference -0.26, 95% CI -0.68 to 0.15, P=.21), number of mature oocytes retrieved (mean difference 0.31, 95% CI -0.14 to 0.75, P=.18), fertilization rate (OR 0.99, 95% CI 0.87-1.11, P=.83), implantation rate (OR 0.92, 95% CI 0.84-1.00, P=.06), ongoing pregnancy rate (OR 0.95, 95% CI 0.86-1.06, P=.40), or live-birth rate (OR 0.95, 95% CI 0.78-1.17, P=.63). A subanalysis based on country of origin and vaccine type was also performed for the primary and secondary outcomes and did not change the study results.

CONCLUSION: Vaccination against COVID-19 is not associated with different fertility outcomes in patients undergoing assisted reproductive technologies.

SYSTEMATIC REVIEW REGISTRATION: PROSPERO, CRD42023400023.

PMID:37441788 | DOI:10.1097/AOG.0000000000005310

J Chem Theory Comput. 2023 Jul 13. doi: 10.1021/acs.jctc.3c00285. Online ahead of print.

ABSTRACT

Many simulation methods concerning solvated molecules are based on the assumption that the solvated species and the solvent can be characterized by some representative structures of the solute and some embedding potential corresponding to this structure. While the averaging of the solvent configurations to obtain an embedding potential has been studied in great detail, this hinges on a single solute structure representation. This assumption is re-examined and generalized for conformationally flexible solutes and tested on 4 nonrigid systems. In this generalized approach, the solute is characterized by a set of representative structures and the corresponding embedding potentials. The representative structures are identified by means of subdividing the statistical ensemble, which in this work is generated by a constant-temperature molecular dynamics simulation. The embedding potential defined in the Frozen-Density Embedding Theory is used to characterize the average effect of the solvent in each subensemble. The numerical examples concern the vertical excitation energies of protonated retinal Schiff bases in protein environments. It is comprehensively shown that subensemble averaging leads to huge computational savings compared with explicit averaging of the excitation energies in the whole ensemble while introducing only minor errors in the case of the systems examined.

PMID:37441785 | DOI:10.1021/acs.jctc.3c00285