Anomaly Detection for imbalanced datasets with Deep Generative Models

Many important data analysis applications present with severely imbalanced datasets with respect to the target variable. A typical example is medical image analysis, where positive samples are scarce, while performance is commonly estimated against the correct detection of these positive examples. We approach this challenge by formulating the problem as anomaly detection with generative models. We train a generative model without supervision on the `negative' (common) datapoints and use this model to estimate the likelihood of unseen data. A successful model allows us to detect the `positive' case as low likelihood datapoints. In this position paper, we present the use of state-of-the-art deep generative models (GAN and VAE) for the estimation of a likelihood of the data. Our results show that on the one hand both GANs and VAEs are able to separate the `positive' and `negative' samples in the MNIST case. On the other hand, for the NLST case, neither GANs nor VAEs were able to capture the complexity of the data and discriminate anomalies at the level that this task requires. These results show that even though there are a number of successes presented in the literature for using generative models in similar applications, there remain further challenges for broad successful implementation.Comment: 15 pages, 13 figures, accepted by Benelearn 2018 conferenc

Development and field validation of an RT-LAMP assay for the rapid detection of chikungunya virus in patient and mosquito samples

Objectives: We aimed to develop a reverse transcription loop-mediated isothermal amplification (RT-LAMP) platform for the rapid detection of CHIKV in both patient and mosquito samples from Brazil. Methods: We optimized an RT-LAMP assay, then evaluated the sensitivity and specificity using visual detection. In comparison with the RT-qPCR reference method, we validated the utility of this assay as a molecular diagnostic test in a reference laboratory for arbovirus diagnostics using 100 serum samples collected from suspected CHIKV cases. Results: Our RT-LAMP assay specifically detected CHIKV without cross-reactivity against other arboviruses. The limit of detection of our RT-LAMP was estimated in −1.18 PFU (confidence interval [CI] ranging from -2.08 to 0.45), resulting in a similar analytical sensitivity when directly compared to the gold standard RT-qPCR assay. Then, we demonstrate the ability of our RT-LAMP assay to detect the virus in different human specimens (serum, urine, and saliva), and crude lysate of Aedes aegypti mosquitoes in as little as 20-30 minutes and without a separate RNA isolation step. Lastly, we showed that our RT-LAMP assay could be lyophilized and reactivated by adding water, indicating potential for room-temperature storage. Our RT-LAMP had a clinical sensitivity of 100% (95% CI, 90.97% to 100.00%), clinical specificity of 96.72% (95% CI, 88.65% to 99.60%), and overall accuracy of 98.00% (95% CI, 92.96% to 99.76%). Conclusions: Taken together, these findings indicate that the RT-LAMP assay reported here solves important practical drawbacks to the deployment of molecular diagnostics in the field and can be used to improve testing capacity, particularly in low- and middle-income countries

LAG3 genotype of the donor and clinical outcome after allogeneic transplantation from HLA-identical sibling donors

IntroductionThe association of polymorphisms in molecules involved in the immune response (checkpoint inhibitors) with the clinical outcome after allogeneic transplantation (alloHSCT) has been described. Lymphocyte Activation 3 (LAG3) is a surface protein that plays a regulatory role in immunity as an inhibitory immune checkpoint molecule.MethodsTo determine its role in the alloHSCT setting, we analyzed 797 patients transplanted from HLA-identical sibling donors. The LAG3 rs870849 C>T polymorphism was genotyped in donors.ResultsWe detected a higher incidence of severe acute GVHD in patients transplanted from donors with TT genotype (p: 0.047, HR 1.64; 95% CI 1.01 – 2.67). Overall survival (OS) was worse for patients transplanted from donors with the rs870849 CT/TT genotype (0.020; HR, 1.44; 95% CI 1.06 – 1.96), as well as disease-free survival (DFS) (p: 0.002; HR 1.58, 95%CI: 1.18 – 2.14) and transplant-related mortality (TRM) (p< 0.001; HR: 1.88, 95% CI 1.29 – 2.74). When combining the LAG3 rs870849 and the PDCD1 rs36084323 genotypes of the donor, three genetic groups were well defined, allowing a good stratification of the risk of acute GVHD, TRM, OS and DFS.DiscussionWe conclude that the LAG3 genotype of the donor may be considered in donors’ selection. As this selection may be limited in the HLA-identical sibling donor scenario, further studies exploring the impact of LAG3 genotype of the donor in unrelated transplantation are warranted

Estudio del impacto de UGT2B17 y PD-1 en el trasplante alogénico de progenitores hematopoyéticos a partir de donante emparentado HLA idéntico

Study of the impact of UGT2B17 and PD-1 on allogeneic transplantation of hematopoietic progenitors (allo-TPH) from HLA-identical related donor. everal genetic factors can favor the development of graft-versus-host disease (GVHD), despite HLA donor-recipient compatibility; this dissertarion by publications, explores the role of the disparity in the minor histocompatibility antigen (mHag) UGT2B17, the main enzyme involved in the glucuronidation of testosterone and the polymorphisms (SNPs) of Programmed cell-death 1 ( PD-1), a gene encoding co-inhibitory molecules of immune response receptors, capable of modulating the alloreactive capacity to mHag disparities, PD-1 activation triggers the inhibition of T-lymphocyte activation (immunological tolerance), this could translate into a variable incidence of GVHD, overall survival (OS), progression-free survival (PFS) or relapse. The results suggest that, UGT2B17 disparity has a negative impact on HLA-identical donor allo-TPH especially when the donor is male, given that the incidence of severe acute graft-versus-host disease in pairs with UGT2B17 disparity was significantly elevated, resulting in worse overall survival in the group of patients with the UGT2B17 disparity. Additionally, PD-1 genotype plays an important role in the development of graft-versus-host disease in patients undergoing allo-TPH from HLA-identical related donor, as the study detected an increase of the risk of acute graft-versus-host disease grades II to IV in patients who received grafts from donors homozygous for alleles identified as high risk in the multivariate analysisEstudi de l'impacte d'UGT2B17 i PD-1 en el trasplantament al·logènic de progenitors hematopoètics (alo-TPH) a partir de donant emparentat HLA idèntic. Diversos factors genètics poden afavorir l'aparició de la malaltia de l´empelt contra l´hoste (MECH), malgrat la compatibilitat de l'HLA entre donant-receptor; aquesta tesi per publicacions, explora el paper de la disparitat en el antígen menor d'histocompatibilitat (AMiH) UGT2B17, la principal enzima involucrada en la glucuronització de la testosterona i, els polimorfismes (SNPs) de Programmed cell-death 1 (PD-1), gen que codifica molècules coinhibidores de receptors de la resposta immune, capaços de modular la capacitat aloreactiva davant de les disparitats d'AMiH, l'activació de PD-1 desencadena la inhibició de l'activació dels limfòcits T (tolerància immune), això podria traduir-se en incidència variable d' MECH, supervivència global (SG), supervivència lliure de progressió (SLP) o recidives. Els resultats suggereixen que, la disparitat d'UGT2B17 té un impacte negatiu al alo-TPH de donant HLA idèntic quan el donant és home, donat que la incidència de la malaltia empelt contra l´hoste aguda severa en parelles amb la disparitat de UGT2B17 va ser significativament elevada, traduïnt-se en una pitjor supervivència global en el grup de pacients amb la disparitat UGT2B17. Adicionalment, el genotip de PD-1 juga un paper important en el desenvolupament de la malaltia empelt contra l´hoste en pacients sotmesos a alo-TPH de donant emparentat HLA idèntic, donat que a l'estudi es va detectar un increment del risc malaltia empelt contra l´hoste aguda graus II a IV en pacients que van rebre empelts de donants homozigots per a al·lels idenficats como d´alt risc en l´anàlisi multivarinatPrograma de Doctorat en Biologia Molecular, Biomedicina i Salu

Text Deconvolution Saliency (TDS) : a deep tool box for linguistic analysis

International audienceIn this paper, we propose a new strategy , called Text Deconvolution Saliency (TDS), to visualize linguistic information detected by a CNN for text classification. We extend Deconvolution Networks to text in order to present a new perspective on text analysis to the linguistic community. We empirically demonstrated the efficiency of our Text Decon-volution Saliency on corpora from three different languages: English, French, and Latin. For every tested dataset, our Text Deconvolution Saliency automatically encodes complex linguistic patterns based on co-occurrences and possibly on grammatical and syntax analysis

Widespread contamination of SARS‐CoV-2 on highly touched surfaces in Brazil during the second wave of the COVID ‐19 pandemic

Although SARS-CoV-2 surface contamination has been investigated in health care settings, little is known about the SARS-CoV-2 surface contamination in public urban areas, particularly in tropical countries. Here, we investigated the presence of SARS-CoV-2 on high-touch surfaces in a large city in Brazil, one the most affected countries by the COVID-19 pandemic in the world. A total of 400 surface samples were collected in February 2021 in the City of Recife, Northeastern Brazil. A total of 97 samples (24.2%) tested positive for SARS-CoV-2 by RT-qPCR using the CDC-USA protocol. All the collection sites, except one (18/19, 94.7%) had at least one environmental surface sample contaminated. SARS-CoV-2 positivity was higher in public transport terminals (47/84, 55.9%), followed by health care units (26/84, 30.9%), beach areas (4/21, 19.0%), public parks (14/105, 13.3%), supply center (2/21, 9.5%), and public markets (4/85, 4.7%). Toilets, ATMs, handrails, playground, and outdoor gym were identified as fomites with the highest rates of SARS-CoV-2 detection. Taken together, our data provide a real-world picture of SARS-CoV-2 dispersion in highly populated tropical areas and identified critical control points that need to be targeted to break SARS-CoV-2 transmission chains

Donor CTLA-4 Genotype Modulates the Immune Response to Minor Histocompatibility Antigen Mismatches.

Minor histocompatibility antigen (miHA) mismatches have been related to graft-versus-host disease (GVHD) after allogeneic stem cell transplantation, but this association remains controversial due to the lack of consistency in the results obtained by different groups. The CTLA-4 genotype of the donor has been reported to be relevant in the appearance of acute GVHD. We explored the effect of the donor's CTLA-4 genotype in the incidence of acute GVHD associated with HA-1, HA-8, or H-Y miHA mismatches in a large cohort of 1295 patients receiving an allogeneic transplant from an HLA-identical sibling donor. The incidence of acute GVHD was higher if the donor and recipient were mismatched for HA-1, HA-8, or H-Y, but only when the donor had the CTLA-4 rs231775 AA genotype (hazard ratio [HR], 2.18; 95% confidence interval [CI], 1.27 to 3.75; P = .005; HR, 2.11, 95% CI, 1.06 to 4.18; P = .033; and HR, 1.50; 95% CI, 1.05 to 2.15; P = .025, respectively). In contrast, this increased risk of developing acute GVHD was not found when the donor presented the CTLA-4 rs231775 AG or GG genotypes. We conclude that the immune response to specific miHA mismatches is modulated by the CTLA-4 genotype of the donor

A novel predictive approach for GVHD after allogeneic SCT based on clinical variables and cytokine gene polymorphisms.

Despite considerable advances in our understanding of the pathophysiology of graft-versus-host disease (GVHD), its prediction remains unresolved and depends mainly on clinical data. The aim of this study is to build a predictive model based on clinical variables and cytokine gene polymorphism for predicting acute GVHD (aGVHD) and chronic GVHD (cGVHD) from the analysis of a large cohort of HLA-identical sibling donor allogeneic stem cell transplant (allo-SCT) patients. A total of 25 SNPs in 12 cytokine genes were evaluated in 509 patients. Data were analyzed using a linear regression model and the least absolute shrinkage and selection operator (LASSO). The statistical model was constructed by randomly selecting 85% of cases (training set), and the predictive ability was confirmed based on the remaining 15% of cases (test set). Models including clinical and genetic variables (CG-M) predicted severe aGVHD significantly better than models including only clinical variables (C-M) or only genetic variables (G-M). For grades 3-4 aGVHD, the correct classification rates (CCR1) were: 100% for CG-M, 88% for G-M, and 50% for C-M. On the other hand, CG-M and G-M predicted extensive cGVHD better than C-M (CCR1: 80% vs. 66.7%, respectively). A risk score was calculated based on LASSO multivariate analyses. It was able to correctly stratify patients who developed grades 3-4 aGVHD (