Publications by Elisa Ficarra

We introduce Neuro-Symbolic Continual Learning, where a model has to solve a sequence of neuro-symbolic tasks, that is, it has to map sub-symbolic inputs to high-level concepts and compute predictions by reasoning consistently with prior knowledge. Our key observation is that neuro-symbolic tasks, although different, often share concepts whose semantics remains stable over time. Traditional approaches fall short: existing continual strategies ignore knowledge altogether, while stock neuro-symbolic architectures suffer from catastrophic forgetting. We show that leveraging prior knowledge by combining neurosymbolic architectures with continual strategies does help avoid catastrophic forgetting, but also that doing so can yield models affected by reasoning shortcuts. These undermine the semantics of the acquired concepts, even when detailed prior knowledge is provided upfront and inference is exact, and in turn continual performance. To overcome these issues, we introduce COOL, a COncept-level cOntinual Learning strategy tailored for neuro-symbolic continual problems that acquires high-quality concepts and remembers them over time. Our experiments on three novel benchmarks highlights how COOL attains sustained high performance on neuro-symbolic continual learning tasks in which other strategies fail.

Background and objective: The functions of an organism and its biological processes result from the expression of genes and proteins. Therefore quantifying and predicting mRNA and protein levels is a crucial aspect of scientific research. Concerning the prediction of mRNA levels, the available approaches use the sequence upstream and downstream of the Transcription Start Site (TSS) as input to neural networks. The State-of-the-art models (e.g., Xpresso and Basenjii) predict mRNA levels exploiting Convolutional (CNN) or Long Short Term Memory (LSTM) Networks. However, CNN prediction depends on convolutional kernel size, and LSTM suffers from capturing long-range dependencies in the sequence. Concerning the prediction of protein levels, as far as we know, there is no model for predicting protein levels by exploiting the gene or protein sequences. Methods: Here, we exploit a new model type (called Perceiver) for mRNA and protein level prediction, exploiting a Transformer-based architecture with an attention module to attend to long-range interactions in the sequences. In addition, the Perceiver model overcomes the quadratic complexity of the standard Transformer architectures. This work's contributions are 1. DNAPerceiver model to predict mRNA levels from the sequence upstream and downstream of the TSS; 2. ProteinPerceiver model to predict protein levels from the protein sequence; 3. Protein&DNAPerceiver model to predict protein levels from TSS and protein sequences. Results: The models are evaluated on cell lines, mice, glioblastoma, and lung cancer tissues. The results show the effectiveness of the Perceiver-type models in predicting mRNA and protein levels. Conclusions: This paper presents a Perceiver architecture for mRNA and protein level prediction. In the future, inserting regulatory and epigenetic information into the model could improve mRNA and protein level predictions. The source code is freely available at https://github.com/MatteoStefanini/DNAPerceiver.

Ideally, Convolutional Neural Networks (CNNs) should be trained with high quality images with minimum noise and correct ground truth labels. Nonetheless, in many real-world scenarios, such high quality is very hard to obtain, and datasets may be affected by any sort of image degradation and mislabelling issues. This negatively impacts the performance of standard CNNs, both during the training and the inference phase. To address this issue we propose Wise2WipedNet (W2WNet), a new two-module Convolutional Neural Network, where a Wise module exploits Bayesian inference to identify and discard spurious images during the training and a Wiped module takes care of the final classification, while broadcasting information on the prediction confidence at inference time. The goodness of our solution is demonstrated on a number of public benchmarks addressing different image classification tasks, as well as on a real-world case study on histological image analysis. Overall, our experiments demonstrate that W2WNet is able to identify image degradation and mislabelling issues both at training and at inference time, with positive impact on the final classification accuracy.

Computer-aided analysis of biological images typically requires extensive training on large-scale annotated datasets, which is not viable in many situations. In this paper, we present Generative Adversarial Network Discriminator Learner (GAN-DL), a novel self-supervised learning paradigm based on the StyleGAN2 architecture, which we employ for self-supervised image representation learning in the case of fluorescent biological images.

Recent developments have resulted in multiple techniques trying to explain how deep neural networks achieve their predictions. The explainability maps provided by such techniques are useful to understand what the network has learned and increase user confidence in critical applications such as the medical field or autonomous driving. Nonetheless, they typically have very low resolutions, severely limiting their capability of identifying finer details or multiple subjects. In this paper we employ an encoder-decoder architecture with skip connection known as U-Net, originally developed for segmenting medical images, as an image classifier and we show that state of the art explainable techniques applied to U-Net can generate pixel level explanation maps for images of any resolution.

It is estimated that oncogenic gene fusions cause about 20% of human cancer morbidity. Identifying potentially oncogenic gene fusions may improve affected patients’ diagnosis and treatment. Previous approaches to this issue included exploiting specific gene-related information, such as gene function and regulation. Here we propose a model that profits from the previous findings and includes the microRNAs in the oncogenic assessment. We present ChimerDriver, a tool to classify gene fusions as oncogenic or not oncogenic. ChimerDriver is based on a specifically designed neural network and trained on genetic and post-transcriptional information to obtain a reliable classification. The designed neural network integrates information related to transcription factors, gene ontologies, microRNAs and other detailed information related to the functions of the genes involved in the fusion and the gene fusion structure. As a result, the performances on the test set reached 0.83 f1-score and 96% recall. The comparison with state-of-the-art tools returned comparable or higher results. Moreover, ChimerDriver performed well in a real-world case where 21 out of 24 validated gene fusion samples were detected by the gene fusion detection tool Starfusion. ChimerDriver integrates transcriptional and post-transcriptional information in an ad-hoc designed neural network to effectively discriminate oncogenic gene fusions from passenger ones. ChimerDriver source code is freely available at https://github.com/martalovino/ChimerDriver.

Background: The function of non-coding RNA sequences is largely determined by their spatial conformation, namely the secondary structure of the molecule, formed by Watson–Crick interactions between nucleotides. Hence, modern RNA alignment algorithms routinely take structural information into account. In order to discover yet unknown RNA families and infer their possible functions, the structural alignment of RNAs is an essential task. This task demands a lot of computational resources, especially for aligning many long sequences, and it therefore requires efficient algorithms that utilize modern hardware when available. A subset of the secondary structures contains overlapping interactions (called pseudoknots), which add additional complexity to the problem and are often ignored in available software. Results: We present the SeqAn-based software LaRA 2 that is significantly faster than comparable software for accurate pairwise and multiple alignments of structured RNA sequences. In contrast to other programs our approach can handle arbitrary pseudoknots. As an improved re-implementation of the LaRA tool for structural alignments, LaRA 2 uses multi-threading and vectorization for parallel execution and a new heuristic for computing a lower boundary of the solution. Our algorithmic improvements yield a program that is up to 130 times faster than the previous version. Conclusions: With LaRA 2 we provide a tool to analyse large sets of RNA secondary structures in relatively short time, based on structural alignment. The produced alignments can be used to derive structural motifs for the search in genomic databases.