Integrated microRNA and proteome analysis of cancer datasets with MoPC

MicroRNAs (miRNAs) are small molecules that play an essential role in regulating gene expression by post-transcriptional gene silencing. Their study is crucial in revealing the fundamental processes underlying pathologies and, in particular, cancer. To date, most studies on miRNA regulation consider the effect of specific miRNAs on specific target mRNAs, providing wet-lab validation. However, few tools have been developed to explain the miRNAmediated regulation at the protein level. In this paper, the MoPC computational tool is presented, that relies on the partial correlation between mRNAs and proteins conditioned on the miRNA expression to predict miRNA-target interactions in multi-omic datasets. MoPC returns the list of significant miRNA-target interactions and plot the significant correlations on the heatmap in which the miRNAs and targets are ordered by the chromosomal location. The software was applied on three TCGA/CPTAC datasets (breast, glioblastoma, and lung cancer), returning enriched results in three independent targets databases

MiREx: mRNA levels prediction from gene sequence and miRNA target knowledge

Messenger RNA (mRNA) has an essential role in the protein production process. Predicting mRNA expression levels accurately is crucial for understanding gene regulation, and various models (statistical and neural network-based) have been developed for this purpose. A few models predict mRNA expression levels from the DNA sequence, exploiting the DNA sequence and gene features (e.g., number of exons/introns, gene length). Other models include information about long-range interaction molecules (i.e., enhancers/silencers) and transcriptional regulators as predictive features, such as transcription factors (TFs) and small RNAs (e.g., microRNAs - miRNAs). Recently, a convolutional neural network (CNN) model, called Xpresso, has been proposed for mRNA expression level prediction leveraging the promoter sequence and mRNAs’ half-life features (gene features). To push forward the mRNA level prediction, we present miREx, a CNN-based tool that includes information about miRNA targets and expression levels in the model. Indeed, each miRNA can target specific genes, and the model exploits this information to guide the learning process. In detail, not all miRNAs are included, only a selected subset with the highest impact on the model. MiREx has been evaluated on four cancer primary sites from the genomics data commons (GDC) database: lung, kidney, breast, and corpus uteri. Results show that mRNA level prediction benefits from selected miRNA targets and expression information. Future model developments could include other transcriptional regulators or be trained with proteomics data to infer protein levels

Automated segmentation of tissue images for computerized IHC analysis

This paper presents two automated methods for the segmentation ofimmunohistochemical tissue images that overcome the limitations of themanual approach aswell as of the existing computerized techniques. The first independent method, based on unsupervised color clustering, recognizes automatically the target cancerous areas in the specimen and disregards the stroma; the second method, based on colors separation and morphological processing, exploits automated segmentation of the nuclear membranes of the cancerous cells. Extensive experimental results on real tissue images demonstrate the accuracy of our techniques compared to manual segmentations; additional experiments show that our techniques are more effective in immunohistochemical images than popular approaches based on supervised learning or active contours. The proposed procedure can be exploited for any applications that require tissues and cells exploration and to perform reliable and standardized measures of the activity of specific proteins involved in multi-factorial genetic pathologie

Automated DNA Fragments Recognition and Sizing through AFM Image Processing

This paper presents an automated algorithm to determine DNA fragment size from atomic force microscope images and to extract the molecular profiles. The sizing of DNA fragments is a widely used procedure for investigating the physical properties of individual or protein-bound DNA molecules. Several atomic force microscope (AFM) real and computer-generated images were tested for different pixel and fragment sizes and for different background noises. The automated approach minimizes processing time with respect to manual and semi-automated DNA sizing. Moreover, the DNA molecule profile recognition can be used to perform further structural analysis. For computer-generated images, the root mean square error incurred by the automated algorithm in the length estimation is 0.6% for a 7.8 nm image pixel size and 0.34% for a 3.9 nm image pixel size. For AFM real images we obtain a distribution of lengths with a standard deviation of 2.3% of mean and a measured average length very close to the real one, with an error around 0.33%

W2WNet: A two-module probabilistic Convolutional Neural Network with embedded data cleansing functionality

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

A Novel Gaussian Extrapolation Approach for 2D Gel Electrophoresis Saturated Protein Spots

Analysis of images obtained from two-dimensional gel electrophoresis (2D-GE) is a topic of utmost importance in bioinformatics research, since commercial and academic software available currently has proven to be neither completely effective nor fully automatic, often requiring manual revision and refinement of computer generated matches. In this work, we present an effective technique for the detection and the reconstruction of over-saturated protein spots. Firstly, the algorithm reveals overexposed areas, where spots may be truncated, and plateau regions caused by smeared and overlapping spots. Next, it reconstructs the correct distribution of pixel values in these overexposed areas and plateau regions, using a two-dimensional least-squares fitting based on a generalized Gaussian distribution. Pixel correction in saturated and smeared spots allows more accurate quantification, providing more reliable image analysis results. The method is validated for processing highly exposed 2D-GE images, comparing reconstructed spots with the corresponding non-saturated image, demonstrating that the algorithm enables correct spot quantification

A Multi-modal Brain Image Registration Framework for US-guided Neuronavigation Systems - Integrating MR and US for Minimally Invasive Neuroimaging

US-guided neuronavigation exploits the simplicity of use and minimal invasiveness of Ultrasound (US) imaging and the high tissue resolution and signal-to-noise ratio of Magnetic Resonance Imaging (MRI) to guide brain surgeries. More specifically, the intra-operative 3D US images are combined with pre-operative MR images to accurately localise the course of instruments in the operative field with minimal invasiveness. Multi-modal image registration of 3D US and MR images is an essential part of such system. In this paper, we present a complete software framework that enables the registration US and MR brain scans based on a multi resolution deformable transform, tackling elastic deformations (i.e. brain shifts) possibly occurring during the surgical procedure. The framework supports also simpler and faster registration techniques, based on rigid or affine transforms, and enables the interactive visualisation and rendering of the overlaid US and MRI volumes. The registration was experimentally validated on a public dataset of realistic brain phantom images, at different levels of artificially induced deformations

Identifying the oncogenic potential of gene fusions exploiting miRNAs

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