scholarly journals Combining Bayesian Approaches and Evolutionary Techniques for the Inference of Breast Cancer Networks

2017 ◽  
Author(s):  
Stefano Beretta ◽  
Mauro Castelli ◽  
Ivo Gonçalves ◽  
Ivan Merelli ◽  
Daniele Ramazzotti

AbstractGene and protein networks are very important to model complex large-scale systems in molecular biology. Inferring or reverseengineering such networks can be defined as the process of identifying gene/protein interactions from experimental data through computational analysis. However, this task is typically complicated by the enormously large scale of the unknowns in a rather small sample size. Furthermore, when the goal is to study causal relationships within the network, tools capable of overcoming the limitations of correlation networks are required. In this work, we make use of Bayesian Graphical Models to attach this problem and, specifically, we perform a comparative study of different state-of-the-art heuristics, analyzing their performance in inferring the structure of the Bayesian Network from breast cancer data.


Complexity ◽  
2021 ◽  
Vol 2021 ◽  
pp. 1-17
Author(s):  
Qiang Tian ◽  
Rui Wang ◽  
Shijie Li ◽  
Wenjun Wang ◽  
Ou Wu ◽  
...  

Understanding and solving the psychological health problems of college students have become a focus of social attention. Complex networks have become important tools to study the factors affecting psychological health, and the Gaussian graphical model is often used to estimate psychological networks. However, previous studies leave some gaps to overcome, including the following aspects. (1) When studying networks of subpopulations, the estimation neglects the intrinsic relationships among subpopulations, leading to a large difference between the estimated network and the real network. (2) Because of the high cost, previous psychological surveys often have a small sample size, and the psychological description is insufficient. Here, the intrinsic connections among multiple tasks are used, and multitask machine learning is applied to develop a multitask Gaussian graphical model. The psychological networks of the population and subpopulations are estimated based on psychological questionnaire data. This study is the first to apply a psychological network to such a large-scale college student psychological analysis, and we obtain some interesting results. The model presented here is a dynamic model based on complex networks which predicts individual behavior and provides insight into the intrinsic links among various symptoms.



2008 ◽  
Vol 31 (4) ◽  
pp. 19
Author(s):  
I Pasic ◽  
A Shlien ◽  
A Novokmet ◽  
C Zhang ◽  
U Tabori ◽  
...  

Introduction: OS, a common Li-Fraumeni syndrome (LFS)-associated neoplasm, is a common bone malignancy of children and adolescents. Sporadic OS is also characterized by young age of onset and high genomic instability, suggesting a genetic contribution to disease. This study examined the contribution of novel DNA structural variation elements, CNVs, to OS susceptibility. Given our finding of excessive constitutional DNA CNV in LFS patients, which often coincide with cancer-related genes, we hypothesized that constitutional CNV may also provide clues about the aetiology of LFS-related sporadic neoplasms like OS. Methods: CNV in blood DNA of 26 patients with sporadic OS was compared to that of 263 normal control samples from the International HapMap project, as well as 62 local controls. Analysis was performed on DNA hybridized to Affymetrix genome-wide human SNP array 6.0 by Partek Genomic Suite. Results: There was no detectable difference in average number of CNVs, CNV length, and total structural variation (product of average CNV number and length) between individuals with OS and controls. While this data is preliminary (small sample size), it argues against the presence of constitutional genomic instability in individuals with sporadic OS. Conclusion: We found that the majority of tumours from patients with sporadic OS show CN loss at chr3q13.31, raising the possibility that chr3q13.31 may represent a “driver” region in OS aetiology. In at least one OS tumour, which displays CN loss at chr3q13.31, we demonstrate decreased expression of a known tumour suppressor gene located at chr3q13.31. We are investigating the role ofchr3q13.31 in development of OS.



2021 ◽  
Vol 9 (2) ◽  
pp. 42
Author(s):  
Angeliki Andrikopoulou ◽  
Oraianthi Fiste ◽  
Kleoniki Apostolidou ◽  
Efthymia Skafida ◽  
Christos Markellos ◽  
...  

Background: Aromatase inhibitors (AIs) are associated with musculoskeletal pain in one third (20–47%) of breast cancer patients. Recently, CDK4/6 inhibitors have emerged as a new therapeutic approach in hormone receptor (HR)-positive breast cancer. While hematological and gastrointestinal toxicities are frequently reported during treatment with CDK4/6 inhibitors, musculoskeletal symptoms are less commonly encountered. Methods: Herein, we present a retrospective study of 47 breast cancer patients who received CDK4/6 inhibitors along with endocrine therapy in our department between 01/01/2018 and 01/09/2020. Results: Median age at diagnosis was 58 years (29–81). Median duration of treatment was 8.76 months (SD: 7.68; 0.47–30.13 months). Median PFS was 24.33 months (95% CI; 1.71–46.96). Overall, toxicity was reported in 61.7% of the cases (29/47). Arthralgia was reported in 6.4% (3/47) of the patients. Hematological toxicity was reported in 51.1% (24/47) of the patients. Neutropenia was the main hematological toxicity observed (86.8%; 22/47) along with anemia (4.3%; 2/47), thrombocytopenia (2.1%; 1/47), and leukopenia (4.2%; 1/24). Conclusions: Though our data reflect a small sample size, we report a reduced arthralgia rate (6.4%) during treatment with CDK4/6 inhibitors compared with that reported in studies of AIs (20–47%).



2021 ◽  
Vol 39 (15_suppl) ◽  
pp. e18687-e18687
Author(s):  
Maya Leiva ◽  
Angela Pennisi ◽  
Kathleen Kiernan Harnden ◽  
Patricia Conrad Rizzo ◽  
Lauren Ann Mauro

e18687 Background: The long-acting injectable G-CSF, pegfilgrastim and its biosimilars have historically been given to patients 24 hours following the administration of myelosuppressive chemotherapy for either primary or secondary prophylaxis of febrile neutropenia (FN). Previous literature has indicated that pegfilgrastim administration prior to 24 hours post chemotherapy, may result in a deepened and prolonged neutropenia due to the increase in circulating granulocytes exposed to chemotherapy. With the onset of the COVID-19 pandemic and to reduce potential SAR-CoV-2 exposure to cancer patients on therapy, we implemented same day administration of injectable pegfilgrastim-cbqv among select breast cancer patients receiving myelosuppressive chemotherapy regimens from March 2020 – February 2021. Methods: Utilizing retrospective EHR chart reviews, 55 patients among 4 medical oncologists in our breast cancer group were identified as meeting the criteria of same day pegfilgrastim-cbqv administration. Inclusion was based on completion of at least 2 consecutive cycles of same day pegfilgrastim-cbqv 6 mg subcutaneous injection for primary or secondary prophylaxis. The selected patient charts were reviewed for the incidence and severity of FN. Among the patients who had documented FN, further subgroup analyses were done regarding baseline characteristics, timing of neutropenia, regimens, regimen sequence, and reported ADRs associated with pegfilgrastim-cbqv. Results: 9 (16.4%) of the 55 patients experienced FN (Grades 3-4) and 6 (10.9%) patients were hospitalized. There were no Grade 5 events and none had therapy discontinued due to FN. 8 (88.9%) of the patients experienced FN between cycles 1 and 2. Of note, there were no cases of COVID-19 among the 9 patients who had an episode of FN. 52 (94.5%) of the 55 patients received treatment with curative intent and 3 (5.5%) had metastatic disease on a subsequent line of therapy. The median age was 49.1 years (range 29-71) and patients were 56.4% Caucasian, 18.1% Black or African American, 12.7% Asian, and 12.7% Hispanic/Latina. Conclusions: Based on the retrospective data analysis, same day pegfilgrastim-cbqv appears to be a safe and effective option in the primary and secondary prophylaxis of FN with myelosuppressive standard of care chemotherapy used in breast cancer treatment. Though our review was limited by a relatively small sample size and confined to younger (49.1 median age) breast cancer patients, this opens the door to further re-evaluation of same day pegfilgrastim-cbqv administration in other patient populations. In a post pandemic treatment world, this slight change in practice has the potential to reduce patient financial toxicity associated with multiple medical visits, provide an alternative to on-body injector formulations, and ensure treatment adherence.



2021 ◽  
Author(s):  
Taku Monjo ◽  
Masaru Koido ◽  
Satoi Nagasawa ◽  
Yutaka Suzuki ◽  
Yoichiro Kamatani

Spatial transcriptomics is an emerging technology requiring costly reagents and considerable skills, limiting the identification of transcriptional markers related to histology. Here, we show that predicted spatial gene-expressions in unmeasured regions and tissues can enhance biologists' histological interpretations. We developed the Deep learning model for Spatial gene Clusters and Expression, DeepSpaCE and confirmed its performance using the spatial-transcriptome profiles and immunohistochemistry images of consecutive human breast cancer tissue sections. For example, the predicted expression patterns of SPARC, an invasion marker, highlighted a small tumor-invasion region that is difficult to identify using raw data of spatial transcriptome alone because of a lack of measurements. We further developed semi-supervised DeepSpaCE using unlabeled histology images and increased the imputation accuracy of consecutive sections, enhancing applicability for a small sample size. Our method enables users to derive hidden histological characters via spatial transcriptome and gene annotations, leading to accelerated biological discoveries without additional experiments.



Doctor Ru ◽  
2021 ◽  
Vol 20 (9) ◽  
pp. 43-47
Author(s):  
E.Yu. Mozheyko ◽  
◽  
O.V. Petryaeva ◽  
◽  
◽  
...  

Objective of the Review: To collect information, analyse and evaluate previous studies in the use of biofeedback in neurological patients. Key Points. Despite the wide practical application and a lot of available publications, the level of evidence of this method is low because of a small sample size and the challenges with biofeedback mechanism description. A review of various types of biocontrol, its mechanisms and developments shows that drug-free therapy using only patient’s resources (organic, psychological, emotional and volitional) can activate the mechanisms of neuroplasticity, which are poorly studied. Still, it does not prevent from using biocontrol for the therapy of patients and/or prevention of various diseases in healthy population. Conclusion. Biofeedback therapy has proven to be a safe, relatively efficient and easy-to-use method. However, organisation of a large-scale double blind randomized trial is one of the predominant directions in the future. Keywords: biofeedback, biocontrol, neurofeedback, biofeedback therapy.



2021 ◽  
Author(s):  
Xin Chen ◽  
Qingrun Zhang ◽  
Thierry Chekouo

Abstract Background: DNA methylations in critical regions are highly involved in cancer pathogenesis and drug response. However, to identify causal methylations out of a large number of potential polymorphic DNA methylation sites is challenging. This high-dimensional data brings two obstacles: first, many established statistical models are not scalable to so many features; second, multiple-test and overfitting become serious. To this end, a method to quickly filter candidate sites to narrow down targets for downstream analyses is urgently needed. Methods: BACkPAy is a pre-screening Bayesian approach to detect biological meaningful clusters of potential differential methylation levels with small sample size. BACkPAy prioritizes potentially important biomarkers by the Bayesian false discovery rate (FDR) approach. It filters non-informative sites (i.e. non-differential) with flat methylation pattern levels accross experimental conditions. In this work, we applied BACkPAy to a genome-wide methylation dataset with 3 tissue types and each type contains 3 gastric cancer samples. We also applied LIMMA (Linear Models for Microarray and RNA-Seq Data) to compare its results with what we achieved by BACkPAy. Then, Cox proportional hazards regression models were utilized to visualize prognostics significant markers with The Cancer Genome Atlas (TCGA) data for survival analysis. Results: Using BACkPAy, we identified 8 biological meaningful clusters/groups of differential probes from the DNA methylation dataset. Using TCGA data, we also identified five prognostic genes (i.e. predictive to the progression of gastric cancer) that contain some differential methylation probes, whereas no significant results was identified using the Benjamin-Hochberg FDR in LIMMA. Conclusions: We showed the importance of using BACkPAy for the analysis of DNA methylation data with extremely small sample size in gastric cancer. We revealed that RDH13, CLDN11, TMTC1, UCHL1 and FOXP2 can serve as predictive biomarkers for gastric cancer treatment and the promoter methylation level of these five genes in serum could have prognostic and diagnostic functions in gastric cancer patients.



2021 ◽  
Vol 39 (15_suppl) ◽  
pp. 10598-10598
Author(s):  
Reshma L. Mahtani ◽  
Alexander Niyazov ◽  
Katie Lewis ◽  
Lucy Massey ◽  
Alex Rider ◽  
...  

10598 Background: African Americans (AA) have the highest breast cancer (BC) mortality rate. Access to treatment is a known contributing factor. In the past 4 years, several targeted therapies for HER2- BC have become available which require testing for specific biomarkers. This study assessed the impact of race on biomarker testing rates in HER2- ABC pts receiving treatment in the US. Methods: Oncologists were recruited to abstract data from medical charts for the next 8-10 pts receiving treatment with HER2- ABC during Sept 2019-Apr 2020. Pts records were stratified by race and categorized into 3 mutually exclusive cohorts [White/Caucasian (White), AA, Other]. The other race cohort was excluded from this analysis due to small sample size. Differences in pt demographics/clinical characteristics were analyzed via Fisher’s exact tests. Testing rates for actionable biomarkers (i.e. BRCA1/2, PIK3CA, PD-L1) were compared between White and AA pts utilizing logistic regressions controlling for age, known family history of a BRCA-related cancer, hormone receptor (HR) status and practice setting (academic vs. community). Further analyses by age will be presented. Results: This analysis included 378 pts records, provided by 40 oncologists. Mean age was 64 years; 77% had HR+/HER2- ABC; 20% had advanced triple negative breast cancer (TNBC), 3% had ABC with an unknown HR status. Compared to White pts, AA pts were significantly more likely to have advanced TNBC (27% vs. 18%, p<0.05). Compared to White pts, AA pts had significantly lower BRCA1/2 mutation (mut) testing rates (Table). Numerically lower rates of PIK3CAmut and PD-L1 testing were observed among AA pts (Table). BRCA1/2mut positivity rate (germline [g] and/or somatic [s]) was higher among AA vs. White pts (30% vs. 22%). Positivity rate for PIK3CAmut was lower for AA vs. White pts (8% vs. 11%). Conclusions: A higher than expected BRCA1/2mut positivity rate was observed than previously reported in the literature. This is likely because this analysis included s BRCA1/2mut and represented a high risk pt population. Across all biomarkers assessed, AA pts had lower testing rates than White pts. This suggests racial disparities in testing rates of actionable biomarkers. Consistent with guidelines, and with the increased availability of targeted therapies, focused efforts should be developed to increase biomarker testing in AA pts. Funding: Pfizer Biomarker Testing Rates by Race.[Table: see text]



2019 ◽  
Vol 33 ◽  
pp. 205873841985587
Author(s):  
Luca Scapoli ◽  
Francesco Carinci ◽  
Annalisa Palmieri ◽  
Francesca Cura ◽  
Alessandro Baj ◽  
...  

Non-syndromic cleft lip with or without cleft palate (nsCL/P) is a frequent orofacial malformation. The comparison of concordance rate observed in monozygotic and dizygotic twins supports high level of heritability and a strong genetic component. However, phenotype concordance for orofacial cleft in monozygotic twins is about 50%. The aim of the present investigation was to detect postzygotic events that may account for discordance in monozygotic twins. High-density SNP microarrays hybridization was used to genotype two pairs of monozygotic twins discordant for nsCL/P. Discordant SNP genotypes and copy number variants were analyzed to identify genetic differences responsible of phenotype discrepancy. A number of differences were observed, none involving known nsCL/P candidate genes or genomic regions. Considering the limitation of the study, related to the small sample size and to the large-scale investigation method, the results suggest that the detection of discordant events in other monozygotic twin pairs would be remarkable and warrant further investigations.



2017 ◽  
Vol 19 (1) ◽  
Author(s):  
Giorgio E. M. Melloni ◽  
Luca Mazzarella ◽  
Loris Bernard ◽  
Margherita Bodini ◽  
Anna Russo ◽  
...  


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