Original Signer Research Articles

Fractional Fourier Transform and Transferred CNN Based on Tensor for Hyperspectral Anomaly Detection

Most of the algorithms for hyperspectral anomaly detection (AD) are based on the original spectral signatures which may suffer noise contamination. In recent years, some AD algorithms based on deep learning (DL) and tensor have achieved satisfactory results. In this letter, an algorithm using fractional Fourier transform (FrFT) and transferred convolutional neural network based on tensor (FrFTTCNNT) is proposed for hyperspectral AD. First, the test block of each test point in hyperspectral imagery (HSI) is transformed into 1-D vector and a higher dimensional data set with more spatial information is obtained. Furthermore, the higher dimensional data set is dimensionally reduced by principal component analysis (PCA) to remove the redundancy of spectral bands. Then, the lower dimensional data set after PCA is transformed by FrFT and the nonstationary noise in the fractional Fourier domain (FrFD) can be better suppressed which may increase the discrimination between background and targets. Finally, in the FrFD, transferred CNN based on tensor (TCNNT) is employed for the final results. Experiments conducted on three hyperspectral data sets show the superiority of the proposed FrFTTCNNT.

A Quantum Multi-Agent Blind Signature Scheme with Unordered Signatures

With the development of information society, network security problems are becoming more and more serious, and digital signature as an authentication method is widely used in many fields such as information security and e-commerce, mainly to solve security problems such as forgery, repudiation, impersonation and tampering [1]. The latest quantum technology can overcome a series of difficult problems of classical digital signatures in a very short time. In this paper, we propose a quantum multiproxy blind signature scheme, in which the original signer is unable to sign the document himself, and delegates multiple proxy signers to sign and verify the document, and the signature order of the proxy signers is not restricted. The scheme adopts techniques such as Unitary transformation and Hadamard gate, and uses quantum key distribution protocol to ensure its security, which improves the efficiency of signature, ensures the security of signature, and has certain anti-attack capability.

Learning a superficial correlated representation using a local mapping strategy for bearing performance degradation assessment

As a prime technique for proactive maintenance, bearing performance degradation assessment (PDA), which aims to build a health index (HI) to assess the performance degradation process, has drawn more and more attention in recent years. To construct an HI of high quality, we propose a novel and robust fuzzy c-means (FCM) model, based on locally linear embedding (LLE), that aims to learn a superficial correlated representation using a local mapping strategy. First, a great mass of commonly used features from the time-domain, the frequency-domain, and the time–frequency domain are extracted from the original vibration signature. Features are then implemented to obtain the initial dimensions by maximum likelihood estimation (MLE). Subsequently, local mapping produced by LLE with the initial dimensions extracts the underlying manifold structure from all the remaining features, and a superficial correlated representation is obtained, generated from the space expanded by the features. Finally, an HI based on the subjection of the FCM model is used to assess the bearing degradation process. To validate the superiority of the proposed method, it is compared with three advanced PDA models through experiments on three public datasets. A comparison of the proposed method with those of the other studies confirms the potential of MLE-LLE as an effective feature-fusion tool for the PDA of bearings.

Exploring relationships between shock-induced microstructures and H2O and Cl in apatite grains from eucrite meteorites

The abundance and isotopic composition of volatile elements in meteorites is critical for understanding planetary evolution, given their importance in a variety of geochemical processes. There has been significant interest in the mineral apatite, which occurs as a minor phase in most meteorites and is known to contain appreciable amounts of volatiles (up to wt. % F, Cl, and OH). Impact-driven shock metamorphism, pervasive within many meteorites, can potentially modify the original signatures of volatiles through processes such as devolatilization and diffusion. In this study, we investigate the microstructures of apatite grains from six eucrites across a broad range of shock stages (S1–S5) using electron backscatter diffraction (EBSD) to explore shock-induced crystallographic features in apatite. New Cl and H abundance and isotopic composition data were collected on moderate to highly shocked samples (S3-S5) by Nano Secondary Ion Mass Spectrometry (NanoSIMS). Previously reported volatile data for S1 and S2 eucrites were integrated with EBSD findings in this study. Our findings indicate that apatite microstructures become increasingly more complex at higher shock stages. At low shock stages (S1–S2) samples display brecciation and fracturing of apatite. Samples in S3 and S4 display increasing crystal plastic deformation indicated by increasing spread in pole figures. At the higher shock stages (S4/S5) there is potential recrystallisation demonstrated by an increased density of subgrain boundaries. The Cl content and δ37Cl values of highly-shocked apatite grains range from ∼940 to 1410 ppm and −3.38 to +7.70‰, respectively, within the range observed in less-shocked eucrites. In contrast, H2O abundances are more variable (from 186 to ∼4010 ppm), however, the measured water content still falls within the range previously reported for low-shock eucrites. The measured δD values range from −157 to +163‰, also within the range of values from known low-shock basaltic eucrites. Weighted averages for both isotopic systems (δD −122 ± 20‰, δ37Cl + 1.76 ± 0.66‰) are consistent with the range displayed in other inner Solar System bodies. NanoSIMS isotope images of apatite grains display heterogeneity in their Cl abundance at the nanoscale which increases in complexity with shock stage. This increasing complexity, however, does not correlate with deformation microstructures observed in EBSD or with the Cl isotopic composition at either an inter-grain or intra-grain scale. These findings are similar to analyses of variably shocked lunar apatite and, therefore, apatite appears to be a robust recorder of Cl and H (at least at spatial resolution and precision currently achievable by NanoSIMS) on airless bodies, despite intensive shock.

A scalable post-quantum hash-based group signature

We present a construction for hash-based one-time group signature schemes, and develop a traceable post-quantum multi-time group signature upon it. A group signature scheme allows group members to anonymously sign a message on behalf of the entire group. The signatures are unforgeable, and the scheme enables authorized openers to trace the signature back to the original signer when needed. Our construction utilizes three nested layers to build the group signature scheme. The first layer performs the key-management task; it deploys a transversal design to assign keys to the group members and the openers, establishing anonymity and providing the construction with traceability. The second layer utilizes sets of hash values, hash pools, to build the group public verification key and to connect group members together. The final layer uses a post-quantum hash-based signature scheme, that adds unforgeability to our construction. We extend our scheme to multi-time signatures using Merkle trees and show that this process maintains the scalability property of Merkle-based signatures, while it supports the group members signing any number of messages.

Off-line signature verification using elementary combinations of directional codes from boundary pixels

Verifying the genuineness of official documents, such as bank checks, certificates, contract forms, bonds, etc., remains a challenging task when it comes to accuracy and robustness. Here, the genuineness is related to the degree of match of the signature contained in the documents relating to the original signatures of the authorized person. Signatures of authorized persons are considered known in advance. In this paper, a novel feature set is introduced based on quasi-straightness of boundary pixel runs for signature verification. We extract the quasi-straight line segments using elementary combinations of the directional codes from the signature boundary pixels and subsequently we obtain the feature set from various quasi-straight line classes. The quasi-straight line segments provide a blending of straightness and small curvatures resulting in a robust feature set for the verification of signatures. We have used Support Vector Machine (SVM) for classification and have shown results on standard signature datasets like CEDAR (Center of Excellence for Document Analysis and Recognition) and GPDS-100 (Grupo de Procesado Digital de la Senal). The results establish how the proposed method outperforms the existing state of the art.

Redactable Signature with Compactness from Set-Commitment

Redactable signature allows anyone to remove parts of a signed message without invalidating the signature. The need to prove the validity of digital documents issued by governments is increasing. When governments disclose documents, they must remove private information concerning individuals. Redactable signature is useful for such a situation. However, in most redactable signature schemes, to remove parts of the signed message, we need pieces of information for each part we want to remove. If a signed message consists of l elements, the number of elements in an original signature is at least linear in l. As far as we know, in some redactable signature schemes, the number of elements in an original signature is constant, regardless of the number of elements in a message to be signed. However, these constructions have drawbacks in that the use of the random oracle model or generic group model. In this paper, we construct an efficient redactable signature to overcome these drawbacks. Our redactable signature is obtained by combining set-commitment proposed in the recent work by Fuchsbauer et al. (JoC 2019) and digital signatures.

FP05.02 An Early Detection and Prognostic Blood Biomarkers Signature for Malignant Pleural Mesothelioma Based on Targeted Proteomics

We have investigated an academically developed targeted proteomics signature for the early detection and for prognostication of malignant pleural mesothelioma (MPM) from the blood. We have studied a multicenter cohort of more than 400 MPM patients and asbestos exposed donors. Serum samples were processed on 96-well plates for enrichment of N-linked glycoproteins before analysis by liquid-chromatography mass spectrometry (LC-MS) based targeted proteomics for a multiplexed peptide biomarkers signature. We have verified the use of a multiplexed MPM proteomics signature identified in our previous work in cell lines and blood (the original signature was composed of seven peptides, the current signature is a reduced version of six peptides). The multiplexing approach offered by LC-MS proteomics in serum allowed to increase the discriminatory capacity of the signature over the single biomarkers. The proteomics signature presented an AUC of 0.738 and for early stage MPM (stage I/II) AUC was 0.765. This performance was comparable to what we observed using well established and commercially optimized MPM blood biomarkers, underlying the potential of our academic developed strategy once optimized for routine clinical use. The signature presented a negative-likelihood ratio of 0.11 for early stage MPM, highlighting the sensitivity of the approach and its potential utility for MPM early detection strategies, once integrated with complementary MPM biomarkers with high specificity. In addition, the proteomics signature was able to significantly separate high and low risk groups of MPM patients based on their survival (HR of 1.659), supporting in this way treatment decisions based on patients prognosis. The targeted proteomics signature in blood represents an additional diagnostic approach for MPM early detection and treatment decisions.

Tracing groundwater circulation in a valuable mineral water basin with geochemical and isotopic tools: the case of FERRARELLE, Riardo basin, Southern Italy.

The Riardo basin hosts groundwater exploited for the production of high quality, naturally sparkling, bottled water (e.g., Ferrarelle water), and circulating in a system constituted by highly fractured Mesozoic carbonates, overlain by more impervious volcanic rocks of the Roccamonfina complex. The two formations are locally in hydraulic connection and dislocated by deep-rooted faults. The study aimed at elucidating groundwater origin and circulation, using isotopic tracers (δ18O, δ2H, δ11B and 87Sr/86Sr) coupled to groundwater dating (Tritium, CFCs and SF6). Besides recharge by local precipitation over the Riardo hydrogeological basin, stable isotope ratios in water indicated an extra-basin recharge, likely from the elevated surrounding carbonate reliefs (e.g., Maggiore and Matese Mts.). The mineralization process, promoted by the deep CO2 flux, controls the B and Sr contents. However, their isotopic ratios did not allow discriminating between circulation in the volcanic and in the carbonate aquifers, as in the latter the isotopic composition differed from the original marine signature. Groundwater model ages ranged from ~ 30 years for the volcanic endmember to > 70 years for the deep, mineralized end-member, with longer circuits recharged at higher elevations. Overall, the results of this study were particularly relevant for mineral water exploitation. A recharge from outside the hydrogeological basin could be evidenced, especially for the more mineralized and valuable groundwater, and an active recent recharge was detected for the whole Riardo system. Both findings will contribute to the refinement of the hydrogeological model and water budget, and to a sustainable development of the resource.Supplementary informationThe online version contains supplementary material available at 10.1007/s10653-021-00845-x.

Comment on Security and Improvement of Partial Blind Signature Scheme and Revocable Certificateless Signature Scheme

Partial blind signature scheme (BLD-SS) can protect the specific content of the signed message by adding factor to blind the signed message and can also prevent the misuse of the signature by adding common information negotiated in advance. Revocable certificateless signature scheme (RCSS) can prevent the user’s privacy from leaking by adding time key in the signature process and signature verification process. BLD-SS and RCSS both have wide applications in electronic-voting, electronic-cash system and other fields. In this paper, it presents a security analysis on a partial blind signature scheme and a revocable signature scheme proposed recently. It points out that the BLD-SS does not satisfy the unforgeability. A malicious user can forge a partial blind signature on any message and any common information without known from PKG (Private Key Generation). It also shows that the RCSS does not satisfy the unforgeability. A malicious enemy can forge a signature on any message and on any user. The PKG also cannot update the time key immediately when a user’s key is leaked or his identity is expired. In order to overcome these problems, it proposes some simple improvement methods which are almost the same efficiency with the original signature scheme.

Upper Aptian-lower albian seawater composition and OAEs: Geochemistry of Agua Salada and Lampazos Formations, Sonora, Mexico

Upper Aptian-lower Albian seawater composition changes and redox conditions in limestones of the Agua Salada and Lampazos formations in Mexico were investigated by data of major oxides, trace elements, rare-earth elements, and stable isotopes. Most limestones of the Agua Salada Formation (Group 1) show REE + Y patterns consistent with precipitation from seawater whereas limestones from the upper part of the Agua Salada and Lampazos formations (Group 2) have non-seawater-like REE + Y patterns. The relationship among REE and major and trace elements indicates that contamination by detrital input is the main source of REEs, followed by Fe-oxyhydroxides. The variations in Ce anomalies were influenced by paleo-redox conditions. The carbon isotope values, low Mn/Sr ratio and absence of correlation between δ13C vs δ18O values suggest that δ13C retained its original marine signatures during diagenesis. The δ13C curve has several significant negative isotopic excursions in upper Aptian-lower Albian strata. The variations in δ13C values and their negative excursions, fossil evidence, positions of δ13C segments, and correlation of this curve with global reference curves permits documentation of OAE 1 b and the associated sub-events such as Jacob, Kilian, Paquier and Leenhardt sub-events.

Variations of the East Asian monsoon over the past 800 kyr constrained by the boron isotope composition of paleo-rainwater inferred from loess-paleosol deposits in NE China

Based on a study of the boron (B) isotope geochemistry of the loess-paleosol sequence of the Niuyangzigou section (NYZG) in Northeast (NE) China, the boron isotopic composition of paleo-rainwater (δ11Bpr) is used for the first time as a potential proxy for tracing changes in the East Asian summer monsoon (EASM) since the mid-Pleistocene. The acid-soluble phase of loess in NE China, which is characteristically a sandy loess, has lower boron concentrations (0.26 to 0.89 μg/g) and more positive δ11B values, from −12.1‰ to +9.4‰, compared to the loess of the Chinese Loess Plateau (CLP). According to the mass balance of boron accumulation from three distinct sources, a mathematical inversion calculation is used to quantify the proportion of boron from each source and to capture the original δ11Bpr signature. The resulting δ11Bpr values range from +6.8 ± 0.95‰ in loess layers to +17.3 ± 3.32‰ in paleosol layers, and the boron accumulated in loess-paleosol layers is shown to be mainly from atmospheric precipitation and silicate weathering. Synchronous variations of reconstructed δ11Bpr and other loess-based proxies, both in NE China and in the CLP, are observed over a large spatial range and on several temporal scales. The linkage of δ11Bpr to the intensity of the EASM is attributed to the kinetic boron isotope fractionation associated with vapor-precipitate phase separation along the transport path of moisture-bearing air masses. A Rayleigh fractionation model is proposed to interpret δ11Bpr in terms of the proportion of water vapor loss after multi-step fractionation processes, which is independent of temperature. The monsoon record based on δ11Bpr shows a significant shift at ∼430 ka, implying an abrupt weakening of the EASM after the Mid-Brunhes Event (MBE), which provides evidence for regional disparities in monsoon evolution in response to the MBE. The ice volume in Northern Hemisphere is a possible factor controlling changes in the EASM in NE China over the past 800 kyr.

Cost-Effective Authenticated Data Redaction With Privacy Protection in IoT

In a typical e-healthcare system, it is common for users' physiological data collected by Internet-of-Things (IoT) devices to be processed and shared in a third-party environment. To improve service quality, healthcare data sharing in third-party environments needs to ensure the integrity, source authentication, and privacy of the data. Redactable signature schemes (RSSs) are designed to address this concern over the past decades. More concretely, an RSS allows a signature holder to delete privacy-sensitive parts of the signed data and derive a valid signature for the retained data without any help from the original signer. This also provides a flexible data sharing mechanism in a bandwidth-saving manner. However, almost all of the existing RSSs are built on top of public-key infrastructure (PKI) systems, which involve heavyweight public-key management problems and are not suitable for resource-limited IoT applications. Besides, we argue that the only known PKI independent RSS for IoT has some security flaws and requires a large storage space. In this work, we eliminate some of the costs associated with PKI and certificates (such as key managements and certificate verifications) in traditional RSS and propose the first identity-based RSS satisfying the requirements of protecting the integrity and source authentication with selective disclosure control for healthcare data sharing in IoT. We prove the security of the scheme in the random oracle model under the k-SDH assumption. Theoretical comparison and experimental analysis show that our construction has a practical performance. As an extension, we also discuss how to extend our design to achieve fine-grained redaction control, which provides a feasible strategy for a signer to prevent additional redaction or arbitrary redaction from dishonest signature holders.

A combined model based on stacked autoencoders and fractional Fourier entropy for hyperspectral anomaly detection

ABSTRACT Nowadays, some models based on deep learning (DL) show good performance for hyperspectral anomaly detection (AD). However, most of these models only use original spectral signatures and the ability of signal enhancement and noise suppression may not be satisfactory. The above problems may be solved by transforming to the intermediate domain between the original reflectance spectrum and its Fourier transform based on fractional Fourier entropy (FrFE). In this paper, a combined model based on stacked autoencoders (SAE) and FrFE (CSF) is proposed for hyperspectral AD. First, the optimal fractional Fourier domain (FrFD) of the difference between original hyperspectral imagery (HSI) and its SAE reconstruction is obtained based on FrFE and the sparsity of test points in the optimal FrFD is calculated. Then, the optimal FrFD of the low-dimension dataset acquired through SAE is obtained and spatial sparsity divergence index (SDI) of test points in the optimal FrFD is calculated. Finally, the sparsity and spatial SDI are combined for the final detection result. Experiments performed on four hyperspectral datasets demonstrate the effectiveness of the proposed CSF algorithm.

Fail-Stop Group Signature Scheme

In this study, a fail-stop group signature scheme (FSGSS) that combines the features of group and fail-stop signatures to enhance the security level of the original group signature is proposed. Assuming that FSGSS encounters an attack by a hacker armed with a supercomputer, this scheme can prove that the digital signature is forged. Based on the aforementioned objectives, this study proposes three lemmas and proves that they are indeed feasible. First, how does a recipient of a digitally signed document verify the authenticity of the signature? Second, when a digitally signed document is under dispute, how can the group’s manager determine the identity of the original group member who signed the document, if necessary, for an investigation? Third, how can one prove that the signature is indeed forged following an external attack from a supercomputer? Following an attack, the signature could be proved to be forged without exposing the key. In addition, the ultimate goal of the group fail-stop signature scheme is to stop using the same key immediately after the discovery of a forgery attack; this would prevent the attack from being repeated.

Effects of contamination on whole-rock isochrons in ancient rocks: A numerical modelling approach

Radiometric decay systems have played a crucial role in developing our understanding of the evolution of the early Earth. There are two main types of protocols for isotope measurements in geological materials: (i) bulk dissolution of rocks, or whole-grains and (ii) spatially resolved techniques (laser-ablation or ion-beam). These two approaches have sometimes led to results that are not easily reconciled for early Earth crustal rocks (≥3.6 Ga). While initial radiogenic isotope signatures (e.g. initial 176Hf/177Hf or initial 143Nd/144Nd) obtained from whole-rock protocols are significantly above chondritic values, indicative of extensive chemical differentiation of the mantle before 3.6 Ga, data from spatially resolved analysis of individual mineral growth domains point toward much less dramatic differentiation. This is indicated by the majority of data falling close to models of Earth's mantle that had not experienced major silicate melt removal into the crust. These data show chondritic or sub-chondritic signatures. Interpretations of whole rock isochrons are built on assumptions about the history and relationship of a number of different samples to each other. At the heart of these assumptions, the effects of secondary process–such as metasomatism–on isotopic compositions and consequently on the age and initial ratio of isochrons, are often considered negligible. In order to evaluate the possible effects of metasomatism and metamorphism on co-genetic igneous suites we modelled the impact of contamination by an external component on both the isochron slope (the apparent age) and the isochron intercept (the initial radiogenic isotope signature). A significant outcome is that the age significance of some of the modified isochron arrays remains to a large extent within uncertainty of the original crystallisation age of the igneous suite. In other words, the original age signature is preserved, but with lower precision. The intercept of the isochron, from which the initial isotope ratio is calculated, however is often significantly modified, which has consequences for the interpretation of these signatures. Our results provide an explanation for the discrepancy between whole-rock and spatially-resolved results observed in early Earth material. Lastly, our results, applied to studies of ancient crustal rocks, are interpreted as indicative of no significantly depleted mantle domains before 3.6 Ga, and no Hf–Nd isotope decoupling at that time.

Sub-band invariants of handwritten texts fuzzy fragments

Socio-economic processes informatization is largely implemented by using various documents electronic storage, including scanned handwritten texts or their fragments images, in particular, in the form of officials’ original signatures. Among the very diverse tasks of handwritten documents scans electronic repositories computer analysis, the direction of automatic search for images fragments, that contain outlines of key words of interest, is quite relevant. The search for such fragments is significantly hampered by the variability of the letterforms, even by the same author. Therefore, it is advisable to use a fragment from the analyzed text as an initial sample. Thus, we are talking about the fragments precedent identification. In this case, a complicating factor is the impossibility of using many identical objects in training, and only one is available. Therefore, the problem of forming an artificial sample, which elements preserve some common characteristic property, arises. In this work, the authors substantiated the application adequacy of the original sub-band approach, which is based on the concept of the data segment Euclidean norm sub-band part and the mathematical apparatus of sub-band matrices obtained on this basis. Decision procedures for the handwritten text fragments sub-band identification were developed, including training on a single precedent.

Pairing-Free Identity-Based Proxy Signature Scheme With Message Recovery

In many real-world situations, signature schemes with message recovery plays a very important role to minimize the bandwidth for efficient communications. A proxy signature scheme is a kind of digital signature scheme that allows an original signer to designate his/her signing capacity to a proxy signer. The proxy signer generates a signature on a message on behalf of the original signer. Such signatures are very useful in various applications where the delegation rights is quite common, especially in distributed systems and grid computing. This paper presents a pairing-free proxy signature with message recovery scheme that integrates the advantages of proxy signatures and message recovery in identity based setting. This scheme improves the computational and communicational efficiency due to pairing-free and message recovery features. The proposed scheme is proven secure in the random oracle model under the hardness assumption of the ECDLP. The comparison results shows that the proposed scheme is superior to the related works from the aspect of security and performance.

Using Residual Networks and Cosine Distance-Based K-NN Algorithm to Recognize On-Line Signatures

As a result of the urgent need to immediately identify individuals through the Internet, especially given the Coronavirus (COVID-19) pandemic at present, the recognition of online handwritten signatures has quickly evolved to become an urgent and necessary matter. However, signature identification remains challenging in the pattern recognition field due to intra-class variability and inter-class similarity. Intra-class variability is a characteristic of human behavioural activities, particularly in handwriting where no two handwritten signatures of any person can exactly coincide. The inter-class similarity is also a characteristic of human movement-based activities such as handwritten signatures particularly when the number of writers is large. In this research, an optimized transfer-learning-based architecture is proposed as a highly accurate identification technique for online-signatures using ResNet18 as a feature extraction deep-learning module. The X-Y time-series signals of the signatures were initially converted into images and used in retraining the ResNet18 model to achieve relatively high accuracy. The retrained ResNet18 model was then used to extract features that possess high discriminative distances among different classes of handwritten signatures. The model’s deep layers were searched to determine the best layer that provided the most discriminative features when using a 1-nearest neighbour learning algorithm based on the cosine distance. By using an ensemble of five models trained on rotated versions of the original signatures and using only three training samples from each writer, the classification accuracy achieved 100% when applied on the genuine signatures of public datasets such as SVC 2004 TASK1 and TASK2, and a new proprietary dataset composed of 120 genuine users. When the abovementioned technique was tested on the aggregated version of the aforementioned datasets, the resultant accuracy was still above 99%. Moreover, the robustness of the technique was proven by testing the generated models trained with one dataset with the other two datasets resulting in accuracy above 99% for all combinations.

Longitudinal CITE-Seq profiling of chronic lymphocytic leukemia during ibrutinib treatment: evolution of leukemic and immune cells at relapse

BackgroundIbrutinib, an irreversible Bruton Tyrosine Kinase (BTK) inhibitor, has revolutionized Chronic Lymphocytic Leukemia (CLL) treatment, but resistances to ibrutinib have emerged, whether related or not to BTK mutations. Patterns of CLL evolution under ibrutinib therapy are well characterized for the leukemic cells but not for their microenvironment.MethodsHere, we addressed this question at the single cell level of both transcriptome and immune-phenotype. The PBMCs from a CLL patient were monitored during ibrutinib treatment using Cellular Indexing of Transcriptomes and Epitopes by sequencing (CITE-Seq) technology.ResultsThis unveiled that the short clinical relapse of this patient driven by BTK mutation is associated with intraclonal heterogeneity in B leukemic cells and up-regulation of common signaling pathways induced by ibrutinib in both B leukemic cells and immune cells. This approach also pinpointed a subset of leukemic cells present before treatment and highly enriched during progression under ibrutinib. These latter exhibit an original gene signature including up-regulated BCR, MYC-activated, and other targetable pathways. Meanwhile, although ibrutinib differentially affected the exhaustion of T lymphocytes, this treatment enhanced the T cell cytotoxicity even during disease progression.ConclusionsThese results could open new alternative of therapeutic strategies for ibrutinib-refractory CLL patients, based on immunotherapy or targeting B leukemic cells themselves.