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Boughorbel, S.

Publications and source records attributed to Boughorbel, S..

2 recordsLinked to original sources

On the Depth of Deep Learning Models for Splice Site Identification

The success of deep learning has been shown in various fields including computer vision, speech recognition, natural language processing and bioinformatics. The advance of Deep Learning in Computer Vision has been an important source of inspiration for other research fields. The objective of this work is to adapt known deep learning models borrowed from computer vision such as VGGNet, Resnet and AlexNet for the classification of biological sequences. In particular, we are interested by the task of splice site identification based on raw DNA sequences. We focus on the role of model architecture depth on model training and classification performance.\n\nWe show that deep learning models outperform traditional classification methods (SVM, Random Forests, and Logistic Regression) for large training sets of raw DNA sequences. Three model families are analyzed in this work namely VGGNet, AlexNet and ResNet. Three depth levels are defined for each model family. The models are benchmarked using the following metrics: Area Under ROC curve (AUC), Number of model parameters, number of floating operations. Our extensive experimental evaluation show that shallow architectures have an overall better performance than deep models. We introduced a shallow version of ResNet, named S-ResNet. We show that it gives a good trade-off between model complexity and classification performance.\n\nAuthor summaryDeep Learning has been widely applied to various fields in research and industry. It has been also succesfully applied to genomics and in particular to splice site identification. We are interested in the use of advanced neural networks borrowed from computer vision. We explored well-known models and their usability for the problem of splice site identification from raw sequences. Our extensive experimental analysis shows that shallow models outperform deep models. We introduce a new model called S-ResNet, which gives a good trade-off between computational complexity and classification accuracy.

bioinformatics

IRF4 haploinsufficiency in a family with Whipples disease

The pathogenesis of Whipples disease (WD) remains largely unknown, as WD strikes only a very small minority of the individuals infected with Tropheryma whipplei (Tw). Asymptomatic carriage of Tw is less rare. We studied a large multiplex French kindred, containing four otherwise healthy WD patients (mean age: 76.7 years) and five healthy carriers of Tw (mean age: 55 years). We used a strategy combining genome-wide linkage analysis and whole-exome sequencing to test the hypothesis that WD is inherited in an autosomal dominant (AD) manner, with age-dependent incomplete penetrance. WD was linked to 12 genomic regions covering 27 megabases in the four patients. These regions contained only one very rare non-synonymous variation: the R98W variant of IRF4. The five Tw carriers were heterozygous for R98W. Interferon regulatory factor 4 (IRF4) is a transcription factor with pleiotropic roles in immunity. We showed that R98W was a loss-of-function allele, like only five other exceedingly rare IRF4 alleles of a total of 39 rare and common non-synonymous alleles tested. Furthermore, heterozygosity for R98W led to a distinctive pattern of transcription in leukocytes following stimulation with BCG or Tw. Finally, we found that IRF4 had evolved under purifying selection and that R98W was not dominant-negative, suggesting that the IRF4 deficiency in this kindred was due to haploinsufficiency. Overall, haploinsufficiency at the IRF4 locus selectively underlies WD in this multiplex kindred. This deficiency displays AD inheritance with incomplete penetrance, and chronic carriage probably precedes WD by several decades in Tw-infected heterozygotes.

immunology