We propose the first unified adversarial attack benchmark for Genomic Foundation Models (GFMs), named GERM. Unlike existing GFM benchmarks, GERM offers the first comprehensive evaluation framework to systematically assess the vulnerability of GFMs to adversarial attacks. Methodologically, we evaluate the adversarial robustness of five state-of-the-art GFMs using four widely adopted attack algorithms and three defense strategies. Importantly, our benchmark provides an accessible and comprehensive framework to analyze GFM vulnerabilities with respect to model architecture, quantization schemes, and training datasets. Empirically, transformer-based models exhibit greater robustness to adversarial perturbations compared to HyenaDNA, highlighting the impact of architectural design on vulnerability. Moreover, adversarial attacks frequently target biologically significant genomic regions, suggesting that these models effectively capture meaningful sequence features.
In recent years, we have seen many advancements in wood species identification. Methods like DNA analysis, Near Infrared (NIR) spectroscopy, and Direct Analysis in Real Time (DART) mass spectrometry complement the long-established wood anatomical assessment of cell and tissue morphology. However, most of these methods have some limitations such as high costs, the need for skilled experts for data interpretation, and the lack of good datasets for professional reference. Therefore, most of these methods, and certainly the wood anatomical assessment, may benefit from tools based on Artificial Intelligence. In this paper, we apply two transfer learning techniques with Convolutional Neural Networks (CNNs) to a multi-view Congolese wood species dataset including sections from different orientations and viewed at different microscopic magnifications. We explore two feature extraction methods in detail, namely Global Average Pooling (GAP) and Random Encoding of Aggregated Deep Activation Maps (RADAM), for efficient and accurate wood species identification. Our results indicate superior accuracy on diverse datasets and anatomical sections, surpassing the results of other methods. Our proposal represents a significant advancement in wood species identification, offering a robust tool to support the conservation of forest ecosystems and promote sustainable forestry practices.
Pre-trained large language models demonstrate potential in extracting information from DNA sequences, yet adapting to a variety of tasks and data modalities remains a challenge. To address this, we propose DNAGPT, a generalized DNA pre-training model trained on over 200 billion base pairs from all mammals. By enhancing the classic GPT model with a binary classification task (DNA sequence order), a numerical regression task (guanine-cytosine content prediction), and a comprehensive token language, DNAGPT can handle versatile DNA analysis tasks while processing both sequence and numerical data. Our evaluation of genomic signal and region recognition, mRNA abundance regression, and artificial genomes generation tasks demonstrates DNAGPT's superior performance compared to existing models designed for specific downstream tasks, benefiting from pre-training using the newly designed model structure.
Decoding the linguistic intricacies of the genome is a crucial problem in biology, and pre-trained foundational models such as DNABERT and Nucleotide Transformer have made significant strides in this area. Existing works have largely hinged on k-mer, fixed-length permutations of A, T, C, and G, as the token of the genome language due to its simplicity. However, we argue that the computation and sample inefficiencies introduced by k-mer tokenization are primary obstacles in developing large genome foundational models. We provide conceptual and empirical insights into genome tokenization, building on which we propose to replace k-mer tokenization with Byte Pair Encoding (BPE), a statistics-based data compression algorithm that constructs tokens by iteratively merging the most frequent co-occurring genome segment in the corpus. We demonstrate that BPE not only overcomes the limitations of k-mer tokenization but also benefits from the computational efficiency of non-overlapping tokenization. Based on these insights, we introduce DNABERT-2, a refined genome foundation model that adapts an efficient tokenizer and employs multiple strategies to overcome input length constraints, reduce time and memory expenditure, and enhance model capability. Furthermore, we identify the absence of a comprehensive and standardized benchmark for genome understanding as another significant impediment to fair comparative analysis. In response, we propose the Genome Understanding Evaluation (GUE), a comprehensive multi-species genome classification dataset that amalgamates $36$ distinct datasets across $9$ tasks, with input lengths ranging from $70$ to $10000$. Through comprehensive experiments on the GUE benchmark, we demonstrate that DNABERT-2 achieves comparable performance to the state-of-the-art model with $21 \times$ fewer parameters and approximately $92 \times$ less GPU time in pre-training.
In forensic sciences, blood is a shred of essential evidence for reconstructing crime scenes. Blood identification and classification may help to confirm a suspect, although several chemical processes are used to recreate the crime scene. However, these approaches can have an impact on DNA analysis. A potential application of bloodstain identification and classification using Hyperspectral Imaging (HSI) can be used as substance classification in forensic science for crime scene analysis. Therefore, this work proposes the use of a fast and compact Hybrid CNN to process HSI data for bloodstain identification and classification. For experimental and validation purposes, we perform experiments on a publicly available Hyperspectral-based Bloodstain dataset. This dataset has different types of substances i.e., blood and blood-like compounds, for instance, ketchup, artificial blood, beetroot juice, poster paint, tomato concentrate, acrylic paint, and uncertain blood. We compare the results with state-of-the-art 3D CNN model and examine the results in detail and present a discussion of each tested architecture with limited availability of the training samples (e.g., only 5 % (792 samples) of the data samples are used to train the model, and validated on 5 % (792 samples) data samples and finally blindly tested on 90 % (14260 samples) of the data samples).
Accurate temperature regulation is critical for amperometric DNA analysis to achieve high fidelity, reliability, and throughput. In this work, a 9x6 cell array of mixed-signal CMOS distributed temperature regulators for on-CMOS multi-modal amperometric DNA analysis is presented. Three DNA analysis methods are supported, including constant potential amperometry (CPA), cyclic voltammetry (CV), and impedance spectroscopy (IS). In-cell heating and temperature sensing elements are implemented in standard CMOS technology without post-processing. Using proportional-integral-derivative (PID) control, the local temperature can be regulated to within +/-0.5C of any desired value between 20C and 90C. The two computationally intensive operations in the PID algorithm, multiplication, and subtraction, are performed by an in-cell dual-slope multiplying ADC in the mixed-signal domain, resulting in a small area and low power consumption. Over 95% of the circuit blocks are synergistically shared among the four operating modes, including CPA, CV, IS, and the proposed temperature regulation mode. A 3mmx3mm CMOS prototype fabricated in a 0.13um CMOS technology has been fully experimentally characterized. Each channel occupies an area of 0.06mm2 and consumes 42uW from a 1.2V supply. The proposed distributed temperature regulation design and the mixed-signal PID implementation can be applied to a wide range of sensory and other applications.
String edit distances have been used for decades in applications ranging from spelling correction and web search suggestions to DNA analysis. Most string edit distances are variations of the Levenshtein distance and consider only single-character edits. In forensic applications polymorphic genetic markers such as short tandem repeats (STRs) are used. At these repetitive motifs the DNA copying errors consist of more than just single base differences. More often the phenomenon of ``stutter'' is observed, where the number of repeated units differs (by whole units) from the template. To adapt the Levenshtein distance to be suitable for forensic applications where DNA sequence similarity is of interest, a generalized string edit distance is defined that accommodates the addition or deletion of whole motifs in addition to single-nucleotide edits. A dynamic programming implementation is developed for computing this distance between sequences. The novelty of this algorithm is in handling the complex interactions that arise between multiple- and single-character edits. Forensic examples illustrate the purpose and use of the Restricted Forensic Levenshtein (RFL) distance measure, but applications extend to sequence alignment and string similarity in other biological areas, as well as dynamic programming algorithms more broadly.
DNA sequencing is revolutionising the field of medicine. DNA sequencers, the machines which perform DNA sequencing, have evolved from the size of a fridge to that of a mobile phone over the last two decades. The cost of sequencing a human genome also has reduced from billions of dollars to hundreds of dollars. Despite these improvements, DNA sequencers output hundreds or thousands of gigabytes of data that must be analysed on computers to discover meaningful information with biological implications. Unfortunately, the analysis techniques have not kept the pace with rapidly improving sequencing technologies. Consequently, even today, the process of DNA analysis is performed on high-performance computers, just as it was a couple of decades ago. Such high-performance computers are not portable. Consequently, the full utility of an ultra-portable sequencer for sequencing in-the-field or at the point-of-care is limited by the lack of portable lightweight analytic techniques. This thesis proposes computer architecture-aware optimisation of DNA analysis software. DNA analysis software is inevitably convoluted due to the complexity associated with biological data. Modern computer architectures are also complex. Performing architecture-aware optimisations requires the synergistic use of knowledge from both domains, (i.e, DNA sequence analysis and computer architecture). This thesis aims to draw the two domains together. In this thesis, gold-standard DNA sequence analysis workflows are systematically examined for algorithmic components that cause performance bottlenecks. Identified bottlenecks are resolved through architecture-aware optimisations at different levels, i.e., memory, cache, register and processor. The optimised software tools are used in complete end-to-end analysis workflows and their efficacy is demonstrated by running on prototypical embedded systems.
Background: The huge quantity of data produced in Biomedical research needs sophisticated algorithmic methodologies for its storage, analysis, and processing. High Performance Computing (HPC) appears as a magic bullet in this challenge. However, several hard to solve parallelization and load balancing problems arise in this context. Here we discuss the HPC-oriented implementation of a general purpose learning algorithm, originally conceived for DNA analysis and recently extended to treat uncertainty on data (U BRAIN). The U-BRAIN algorithm is a learning algorithm that finds a Boolean formula in disjunctive normal form (DNF), of approximately minimum complexity, that is consistent with a set of data (instances) which may have missing bits. The conjunctive terms of the formula are computed in an iterative way by identifying, from the given data, a family of sets of conditions that must be satisfied by all the positive instances and violated by all the negative ones; such conditions allow the computation of a set of coefficients (relevances) for each attribute (literal), that form a probability distribution, allowing the selection of the term literals. The great versatility that characterizes it, makes U-BRAIN applicable in many of the fields in which there are data to be analyzed. However the memory and the execution time required by the running are of O(n3) and of O(n5) order, respectively, and so, the algorithm is unaffordable for huge data sets.
We generated genome-wide data from 69 Europeans who lived between 8,000-3,000 years ago by enriching ancient DNA libraries for a target set of almost four hundred thousand polymorphisms. Enrichment of these positions decreases the sequencing required for genome-wide ancient DNA analysis by a median of around 250-fold, allowing us to study an order of magnitude more individuals than previous studies and to obtain new insights about the past. We show that the populations of western and far eastern Europe followed opposite trajectories between 8,000-5,000 years ago. At the beginning of the Neolithic period in Europe, ~8,000-7,000 years ago, closely related groups of early farmers appeared in Germany, Hungary, and Spain, different from indigenous hunter-gatherers, whereas Russia was inhabited by a distinctive population of hunter-gatherers with high affinity to a ~24,000 year old Siberian6 . By ~6,000-5,000 years ago, a resurgence of hunter-gatherer ancestry had occurred throughout much of Europe, but in Russia, the Yamnaya steppe herders of this time were descended not only from the preceding eastern European hunter-gatherers, but from a population of Near Eastern ancestry. Western and Eastern Europe came into contact ~4,500 years ago, as the Late Neolithic Corded Ware people from Germany traced ~3/4 of their ancestry to the Yamnaya, documenting a massive migration into the heartland of Europe from its eastern periphery. This steppe ancestry persisted in all sampled central Europeans until at least ~3,000 years ago, and is ubiquitous in present-day Europeans. These results provide support for the theory of a steppe origin of at least some of the Indo-European languages of Europe.
We propose a strikingly novel, simple, and effective approach to model online user behavior: we extract and analyze digital DNA sequences from user online actions and we use Twitter as a benchmark to test our proposal. We obtain an incisive and compact DNA-inspired characterization of user actions. Then, we apply standard DNA analysis techniques to discriminate between genuine and spambot accounts on Twitter. An experimental campaign supports our proposal, showing its effectiveness and viability. To the best of our knowledge, we are the first ones to identify and adapt DNA-inspired techniques to online user behavioral modeling. While Twitter spambot detection is a specific use case on a specific social media, our proposed methodology is platform and technology agnostic, hence paving the way for diverse behavioral characterization tasks.
Spambot detection in online social networks is a long-lasting challenge involving the study and design of detection techniques capable of efficiently identifying ever-evolving spammers. Recently, a new wave of social spambots has emerged, with advanced human-like characteristics that allow them to go undetected even by current state-of-the-art algorithms. In this paper, we show that efficient spambots detection can be achieved via an in-depth analysis of their collective behaviors exploiting the digital DNA technique for modeling the behaviors of social network users. Inspired by its biological counterpart, in the digital DNA representation the behavioral lifetime of a digital account is encoded in a sequence of characters. Then, we define a similarity measure for such digital DNA sequences. We build upon digital DNA and the similarity between groups of users to characterize both genuine accounts and spambots. Leveraging such characterization, we design the Social Fingerprinting technique, which is able to discriminate among spambots and genuine accounts in both a supervised and an unsupervised fashion. We finally evaluate the effectiveness of Social Fingerprinting and we compare it with three state-of-the-art detection algorithms. Among the peculiarities of our approach is the possibility to apply off-the-shelf DNA analysis techniques to study online users behaviors and to efficiently rely on a limited number of lightweight account characteristics.