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%

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

A novel Gaussian fitting approach for 2D gel electrophoresis saturated protein spots

Analysis of 2D-GE images is a hot topic in bioinformatics research, since currently available commercial and academic software has proven to be not really effective and not completely automatic, often requiring manual revision of spots detection 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, it reveals overexposed areas where spots may be truncated, and plateau regions caused by smeared and overlapped spots. As next, the correct distribution of pixel values in the overexposed areas and plateau regions is recovered by a two-dimensional fitting based on a generalized Gaussian distribution approximating the spots volume. Pixel correction according to the generalized Gaussian curve in saturated and smeared spots allows more accurate quantifications, providing more reliable image analysis results. As validation, we process highly exposed 2D-GE image, containing saturate spots, with respect to the corresponding non-saturated image, confirming that the method can effectively fix the saturated spots and enable correct spots quantification

ClusterFix: A Cluster-Based Debiasing Approach without Protected-Group Supervision

The failures of Deep Networks can sometimes be ascribed to biases in the data or algorithmic choices. Existing debiasing approaches exploit prior knowledge to avoid unintended solutions; we acknowledge that, in real-world settings, it could be unfeasible to gather enough prior information to characterize the bias, or it could even raise ethical considerations. We hence propose a novel debiasing approach, termed ClusterFix, which does not require any external hint about the nature of biases. Such an approach alters the standard empirical risk minimization and introduces a per-example weight, encoding how critical and far from the majority an example is. Notably, the weights consider how difficult it is for the model to infer the correct pseudo-label, which is obtained in a self-supervised manner by dividing examples into multiple clusters. Extensive experiments show that the misclassification error incurred in identifying the correct cluster allows for identifying examples prone to bias-related issues. As a result, our approach outperforms existing methods on standard benchmarks for bias removal and fairness

Achieving the Way for Automated Segmentation of Nuclei in Cancer Tissue Images through Morphology-Based Approach: a Quantitative Evaluation

In this paper we address the problem of nuclear segmentation in cancer tissue images, that is critical for specific protein activity quantification and for cancer diagnosis and therapy. We present a fully automated morphology-based technique able to perform accurate nuclear segmentations in images with heterogeneous staining and multiple tissue layers and we compare it with an alternate semi-automated method based on a well established segmentation approach, namely active contours. We discuss active contours’ limitations in the segmentation of immunohistochemical images and we demonstrate and motivate through extensive experiments the better accuracy of our fully automated approach compared to various active contours implementations

miR-SEA: miRNA Seed Extension based Aligner Pipeline for NGS Expression Level Extraction

The advent of Next Generation Sequencing (NGS) technology has enabled a new major approach for micro RNAs (miRNAs) expression profiling through the so called RNA-Sequencing (RNA-Seq). Different tools have been developed in the last years in order to detect and quantify miRNAs, especially in pathological samples, starting from the big amount of data deriving from RNA sequencing. These tools, usually relying on general purpose alignment algorithms, are however characterized by different sensitivity and accuracy levels and in the most of the cases provide not overlapping predictions. To overcome these limitations we propose a novel pipeline for miRNAs detection and quantification in RNA-Seq sample, miRNA Seed Extension Aligner (miR-SEA), based on an experimental evidence concerning miRNAs structure. The proposed pipeline was tested on three Colorectal Cancer (CRC) RNA-Seq samples and the obtained results compared with those provided by two well-known miRNAs detection tools showing good ability in performing detection and quantification more adherent to miRNAs structure