Methods for interpreting and understanding deep neural networks

Montavon, Gré,goire,Samek, Wojciech,Mü,ller, Klaus-Robert Elsevier 2018 Digital signal processing Vol.73 No.-

<P><B>Abstract</B></P> <P>This paper provides an entry point to the problem of interpreting a deep neural network model and explaining its predictions. It is based on a tutorial given at ICASSP 2017. As a tutorial paper, the set of methods covered here is not exhaustive, but sufficiently representative to discuss a number of questions in interpretability, technical challenges, and possible applications. The second part of the tutorial focuses on the recently proposed layer-wise relevance propagation (LRP) technique, for which we provide theory, recommendations, and tricks, to make most efficient use of it on real data.</P>

Explaining nonlinear classification decisions with deep Taylor decomposition

Montavon, Gré,goire,Lapuschkin, Sebastian,Binder, Alexander,Samek, Wojciech,Mü,ller, Klaus-Robert Elsevier 2017 Pattern recognition Vol.65 No.-

<P><B>Abstract</B></P> <P>Nonlinear methods such as Deep Neural Networks (DNNs) are the gold standard for various challenging machine learning problems such as image recognition. Although these methods perform impressively well, they have a significant disadvantage, the lack of transparency, limiting the interpretability of the solution and thus the scope of application in practice. Especially DNNs act as black boxes due to their multilayer nonlinear structure. In this paper we introduce a novel methodology for interpreting generic multilayer neural networks by decomposing the network classification decision into contributions of its input elements. Although our focus is on image classification, the method is applicable to a broad set of input data, learning tasks and network architectures. Our method called deep Taylor decomposition efficiently utilizes the structure of the network by backpropagating the explanations from the output to the input layer. We evaluate the proposed method empirically on the MNIST and ILSVRC data sets.</P> <P><B>Highlights</B></P> <P> <UL> <LI> A novel method to explain nonlinear classification decisions in terms of input variables is introduced. </LI> <LI> The method is based on Taylor expansions and decomposes the output of a deep neural network in terms of input variables. </LI> <LI> The resulting deep Taylor decomposition can be applied directly to existing neural networks without retraining. </LI> <LI> The method is tested on two large-scale neural networks for image classification: BVLC CaffeNet and GoogleNet. </LI> </UL> </P>

Infrared Study of the Bacterial Autoinducer <i>N</i>-Hexanoyl-Homoserine Lactone (C6-HSL) in the Gas-Phase, Water, and Octanol Solutions

Kim, Jiah,Kim, Seong Keun,Gré,goire, Gilles,Manil, Bruno,Schermann, Jean Pierre American Chemical Society 2011 The Journal of physical chemistry A Vol.115 No.33

<P>The <I>N</I>-hexanoyl-homoserine lactone (C6-HSL) molecule has been investigated by means of infrared multiphoton dissociation (IRMPD) and Fourier-transform infrared spectroscopy (FT-IR) under different conditions in an attempt to mimic biological situations encountered in communication between bacteria for quorum sensing. The protonated molecular ion was studied in the gas-phase that corresponds to a solvent-free situation somewhat analogous to that encountered in the receptor. The simulation of the IRMPD spectrum of the isolated ion was then conducted by means of quantum chemistry calculations in vacuum. In the case of the neutral species, the FT-IR spectra were recorded in D<SUB>2</SUB>O, mimicking the cytosolic and extracellular media as well as in 1-octanol that is often used for simulation of cell membranes. The interpretation was conducted by considering a C6-HSL molecule in its <I>endo</I> or <I>exo</I> conformation hydrogen-bonded to, respectively, six D<SUB>2</SUB>O and four 1-octanol molecules. A satisfying agreement with the experimental FT-IR studies conducted in solution at room temperature was obtained as long as a continuum IEFPCM model was added to the explicit solvent environment.</P><P><B>Graphic Abstract</B> <IMG SRC='http://pubs.acs.org/appl/literatum/publisher/achs/journals/content/jpcafh/2011/jpcafh.2011.115.issue-33/jp205025p/production/images/medium/jp-2011-05025p_0010.gif'></P><P><A href='http://pubs.acs.org/doi/suppl/10.1021/jp205025p'>ACS Electronic Supporting Info</A></P>

FISSION PRODUCT AND ACTINIDE RELEASE FROM THE DEBRIS BED TEST PHEBUS FPT4: SYNTHESIS OF THE POST TEST ANALYSES AND OF THE REVAPORISATION TESTING OF THE PLENUM SAMPLES

A-C. GREGOIRE,D. JACQUEMAIN,G. GR?GOIRE,,P. CARBOL,J-P. GLATZ,D. KNOCHE,D. PAPAIOANNOU,D. SOLATIE,S. VAN WINCKEL,P.D.W. BOTTOMLEY 한국원자력학회 2006 Nuclear Engineering and Technology Vol.38 No.2

Role of radiotherapy fractionation in head and neck cancers (MARCH): an updated meta-analysis

Lacas, Benjamin,Bourhis, Jean,Overgaard, Jens,Zhang, Qiang,Gré,goire, Vincent,Nankivell, Matthew,Zackrisson, Bjö,rn,Szutkowski, Zbigniew,Suwiń,ski, Rafał,Poulsen, Michael,O'Sullivan, Br Elsevier 2017 The Lancet. Oncology Vol.18 No.9

<P><B>Summary</B></P> <P><B>Background</B></P> <P>The Meta-Analysis of Radiotherapy in squamous cell Carcinomas of Head and neck (MARCH) showed that altered fractionation radiotherapy is associated with improved overall and progression-free survival compared with conventional radiotherapy, with hyperfractionated radiotherapy showing the greatest benefit. This update aims to confirm and explain the superiority of hyperfractionated radiotherapy over other altered fractionation radiotherapy regimens and to assess the benefit of altered fractionation within the context of concomitant chemotherapy with the inclusion of new trials.</P> <P><B>Methods</B></P> <P>For this updated meta-analysis, we searched bibliography databases, trials registries, and meeting proceedings for published or unpublished randomised trials done between Jan 1, 2009, and July 15, 2015, comparing primary or postoperative conventional fractionation radiotherapy versus altered fractionation radiotherapy (comparison 1) or conventional fractionation radiotherapy plus concomitant chemotherapy versus altered fractionation radiotherapy alone (comparison 2). Eligible trials had to start randomisation on or after Jan 1, 1970, and completed accrual before Dec 31, 2010; had to have been randomised in a way that precluded prior knowledge of treatment assignment; and had to include patients with non-metastatic squamous cell carcinoma of the oral cavity, oropharynx, hypopharynx, or larynx undergoing first-line curative treatment. Trials including a non-conventional radiotherapy control group, investigating hypofractionated radiotherapy, or including mostly nasopharyngeal carcinomas were excluded. Trials were grouped in three types of altered fractionation: hyperfractionated, moderately accelerated, and very accelerated. Individual patient data were collected and combined with a fixed-effects model based on the intention-to-treat principle. The primary endpoint was overall survival.</P> <P><B>Findings</B></P> <P>Comparison 1 (conventional fractionation radiotherapy <I>vs</I> altered fractionation radiotherapy) included 33 trials and 11 423 patients. Altered fractionation radiotherapy was associated with a significant benefit on overall survival (hazard ratio [HR] 0·94, 95% CI 0·90–0·98; p=0·0033), with an absolute difference at 5 years of 3·1% (95% CI 1·3–4·9) and at 10 years of 1·2% (−0·8 to 3·2). We found a significant interaction (p=0·051) between type of fractionation and treatment effect, the overall survival benefit being restricted to the hyperfractionated group (HR 0·83, 0·74–0·92), with absolute differences at 5 years of 8·1% (3·4 to 12·8) and at 10 years of 3·9% (−0·6 to 8·4). Comparison 2 (conventional fractionation radiotherapy plus concomitant chemotherapy versus altered fractionation radiotherapy alone) included five trials and 986 patients. Overall survival was significantly worse with altered fractionation radiotherapy compared with concomitant chemoradiotherapy (HR 1·22, 1·05–1·42; p=0·0098), with absolute differences at 5 years of −5·8% (−11·9 to 0·3) and at 10 years of −5·1% (−13·0 to 2·8).</P> <P><B>Interpretation</B></P> <P>This update confirms, with more patients and a longer follow-up than the first version of MARCH, that hyperfractionated radiotherapy is, along with concomitant chemoradiotherapy, a standard of care for the treatment of locally advanced head and neck squamous cell cancers. The comparison between hyperfractionated radiotherapy and concomitant chemoradiotherapy remains to be specifically tested.</P> <P><B>Funding</B></P> <P>Institut National du Cancer; and Ligue Nationale Contre le Cancer.</P>

Integrated cladding-pumped multicore few-mode erbium-doped fibre amplifier for space-division-multiplexed communications

Chen, H.,Jin, C.,Huang, B.,Fontaine, N. K.,Ryf, R.,Shang, K.,Gré,goire, N.,Morency, S.,Essiambre, R.-J.,Li, G.,Messaddeq, Y.,LaRochelle, S. Nature Publishing Group 2016 Nature photonics Vol.10 No.8

Space-division multiplexing (SDM), whereby multiple spatial channels in multimode and multicore optical fibres are used to increase the total transmission capacity per fibre, is being investigated to avert a data capacity crunch and reduce the cost per transmitted bit. With the number of channels employed in SDM transmission experiments continuing to rise, there is a requirement for integrated SDM components that are scalable. Here, we demonstrate a cladding-pumped SDM erbium-doped fibre amplifier (EDFA) that consists of six uncoupled multimode erbium-doped cores. Each core supports three spatial modes, which enables the EDFA to amplify a total of 18 spatial channels (six cores × three modes) simultaneously with a single pump diode and a complexity similar to a single-mode EDFA. The amplifier delivers >20 dBm total output power per core and <7 dB noise figure over the C-band. This cladding-pumped EDFA enables combined space-division and wavelength-division multiplexed transmission over multiple multimode fibre spans.

Machine learning analysis of DNA methylation profiles distinguishes primary lung squamous cell carcinomas from head and neck metastases

Jurmeister, Philipp,Bockmayr, Michael,Seegerer, Philipp,Bockmayr, Teresa,Treue, Denise,Montavon, Gré,goire,Vollbrecht, Claudia,Arnold, Alexander,Teichmann, Daniel,Bressem, Keno,Schu¨ller, Ulrich American Association for the Advancement of Scienc 2019 Science translational medicine Vol.11 No.509

<P>Head and neck squamous cell carcinoma (HNSC) patients are at risk of suffering from both pulmonary metastases or a second squamous cell carcinoma of the lung (LUSC). Differentiating pulmonary metastases from primary lung cancers is of high clinical importance, but not possible in most cases with current diagnostics. To address this, we performed DNA methylation profiling of primary tumors and trained three different machine learning methods to distinguish metastatic HNSC from primary LUSC. We developed an artificial neural network that correctly classified 96.4% of the cases in a validation cohort of 279 patients with HNSC and LUSC as well as normal lung controls, outperforming support vector machines (95.7%) and random forests (87.8%). Prediction accuracies of more than 99% were achieved for 92.1% (neural network), 90% (support vector machine), and 43% (random forest) of these cases by applying thresholds to the resulting probability scores and excluding samples with low confidence. As independent clinical validation of the approach, we analyzed a series of 51 patients with a history of HNSC and a second lung tumor, demonstrating the correct classifications based on clinicopathological properties. In summary, our approach may facilitate the reliable diagnostic differentiation of pulmonary metastases of HNSC from primary LUSC to guide therapeutic decisions.</P>

Long-term Neurologic Outcome After Spinal Ependymoma Resection With Multimodal Intraoperative Electrophysiological Recording: Cohort Study and Review of the Literature

Grégoire P. Chatain,Michael W. Kortz,Stephanie Serva,Keshari Shrestha,Patrick Hosokawa,Timothy H. Ung,Michael Finn 대한척추신경외과학회 2022 Neurospine Vol.19 No.1

Objective: To evaluate how multimodal intraoperative neuromonitoring (IONM) changes during spinal ependymoma (SE) resection correlate with long-term neuro-functional outcomes. Methods: A retrospective analysis of patients aged 18 years or older who underwent surgical resection for SE over a 10-year period was conducted. IONM changes were defined as sustained transcranial motor evoked potential (TcMEP) and/or somatosensory evoked potential (SSEP) signal decrease of 50% or greater from baseline. Primary endpoints were postoperative modified McCormick Neurologic Scale (MNS) scores at postoperative day (POD) < 2, 6 weeks, 1 year, and 2 years. Univariate and multivariate analyses were performed. Results: Twenty-nine patients were identified. Average age was 44.2 ± 15.4 years. Sixteen (55.2%) were male and 13 (44.8%) were female. Tumor location was 10 cervical-predominant (34.5%), 13 thoracic-predominant (44.8%), and 6 lumbar/conus-predominant (20.7%). A majority (69.0%) were World Health Organization grade 2 tumors. Twentyfour patients (82.8%) achieved gross total resection. Thirteen patients (44.8%) had a sustained documented IONM signal change and 10 (34.5%) had a TcMEP change with or without derangement in SSEP. At POD < 2, 6 weeks, 1 year, and 2 years, MNS was significantly higher for those when analyzing subgroups with either any sustained IONM or TcMEP ± SSEP signal attenuation > 50% below baseline (all p < 0.05). Conclusion: Sustained IONM derangements > 50% below baseline, particularly for TcMEP, are significantly associated with higher MNS postoperatively out to 2 years. Intraoperative and postoperative management of these patients warrant special consideration to limit neurologic morbidity.

Relationships between the use of Embden Meyerhof pathway (EMP) or Phosphoketolase pathway (PKP) and lactate production capabilities of diverse Lactobacillus reuteri strains

Grégoire Burgé,Claire Saulou-Bérion,Marwen Moussa,Florent Allais,Violaine Athes,Henry-Eric Spinnler 한국미생물학회 2015 The journal of microbiology Vol.53 No.10

The aims of this study is to compare the growth and glucose metabolism of three Lactobacillus reuteri strains (i.e. DSM 20016, DSM 17938, and ATCC 53608) which are lactic acid bacteria of interest used for diverse applications such as probiotics implying the production of biomass, or for the production of valuable chemicals (3-hydroxypropionaldehyde, 3-hydroxypropionic acid, 1,3-propanediol). However, the physiological diversity inside the species, even for basic metabolisms, like its capacity of acidification or glucose metabolism, has not been studied yet. In the present work, the growth and metabolism of three strains representative of the species diversity have been studied in batch mode. The strains were compared through characterization of growth kinetics and evaluation of acidification kinetics, substrate consumption and product formation. The results showed significant differences between the three strains which may be explained, at least in part, by variations in the distribution of carbon source between two glycolytic pathways during the bacterial growth: the phosphoketolase or heterolactic pathway (PKP) and the Embden-Meyerhof pathway (EMP). It was also shown that, in the context of obtaining a large amount of biomass, DSM 20016 and DSM 17938 strains were the most effective in terms of growth kinetics. The DSM 17938 strain, which shows the more significant metabolic shift from EMP to PKP when the pH decreases, is more effective for lactate production.

Impact of Surgical Timing on Neurological Outcomes for Spinal Arachnoid Cyst: A Single Institution Series

Grégoire P. Chatain,Keshari Shrestha,Michael W. Kortz,Stephanie Serva,Patrick Hosokawa,Ryan C. Ward,Akal Sethi,Michael Finn 대한척추신경외과학회 2022 Neurospine Vol.19 No.2

Objective: Spinal arachnoid cysts (SACs) are rare lesions that often present with back pain and myelopathy. There is a paucity of literature evaluating the impact of surgical timing on neurological outcomes for primary SAC management. To compare long-term neurological outcomes in patients who were managed differently and to understand natural progression of SAC. Methods: We conducted a retrospective analysis of adult patients treated for SAC at our institution from 2010 to 2021, stratified into 3 groups (conservative management only, surgical management, or conservative followed by surgical management). Study outcome measures were neurological outcomes as measured by modified McCormick Neurologic Scale (MNS), postoperative complications, and cyst recurrence. Nonparametric analysis was performed to evaluate differences between groups for selected endpoints. Results: Thirty-six patients with SAC were identified. Eighteen patients were managed surgically. The remaining 18 patients were managed conservatively with outpatient serial imaging, 7 of whom (38.9%) ultimately underwent surgical treatment due to neurological decline. Most common presenting symptoms included back pain (50.0%), extremity weakness (36.1%), and numbness/paresthesia (36.1%). Initial/preoperative (p = 0.017) and 1-year postoperative (p = 0.006) MNS were significantly different between the 3 groups, but not at 6 weeks or 6 months postoperatively (p > 0.05). Additionally, at 1 year, there was no difference in MNS between patients managed surgically and those managed conservatively but ultimately underwent surgery (p > 0.99). Conclusion: Delayed surgical intervention in minimally symptomatic patients does not seem to result in worse long-term neurofunctional outcomes. At 1 year, postoperative MNS were significantly higher in both surgical groups, when compared to the conservative group highlighting worsening clinical picture regardless of preoperative observational status.