This paper presents two automated methods for the segmentation of immunohistochemical tissue images that overcome the limitations of the manual approach as well 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 pathologies.

Texture analysis is a major task in many areas of computer vision and pattern recognition, including biological imaging. Indeed, visual textures can be exploited to distinguish specific tissues or cells in a biological sample, to highlight chemical reactions between molecules, as well as to detect subcellular patterns that can be evidence of certain pathologies. This makes automated texture analysis fundamental in many applications of biomedicine, such as the accurate detection and grading of multiple types of cancer, the differential diagnosis of autoimmune diseases, or the study of physiological processes. Due to their specific characteristics and challenges, the design of texture analysis systems for biological images has attracted ever-growing attention in the last few years. In this paper, we perform a critical review of this important topic. First, we provide a general definition of texture analysis and discuss its role in the context of bioimaging, with examples of applications from the recent literature. Then, we review the main approaches to automated texture analysis, with special attention to the methods of feature extraction and encoding that can be successfully applied to microscopy images of cells or tissues. Our aim is to provide an overview of the state of the art, as well as a glimpse into the latest and future trends of research in this area.

Continuous glucose monitoring systems (CGMSs) allow measuring the blood glycaemic value of a diabetic patient at a high sampling rate, producing a considerable amount of data. These data can be effectively used by machine learning techniques to infer future values of the glycaemic concentration, allowing the early prevention of dangerous hyperglycaemic or hypoglycaemic states and better optimization of the diabetic treatment. Most of the approaches in the literature learn a prediction model from the past samples of the same patient, which needs extensive calibrations and limits the usability of the system. In this paper, we investigate the prediction models trained on glucose signals of a large and heterogeneous cohort of patients and then applied to infer future glucose-level values on a completely new patient. To achieve this purpose, we designed and compared two different types of solutions that were proved successful in many time-series prediction problems based respectively, on non-linear autoregressive (NAR) neural network and on long short-term memory (LSTM) networks. These solutions were experimentally compared with three literature approaches, respectively, based on feed-forward neural networks (FNNs), autoregressive (AR) models, and recurrent neural networks (RNN). While the NAR obtained good prediction accuracy only for short-term predictions (i.e., with prediction horizon within 30 min), the LSTM obtained extremely good performance both for short-and long-term glucose-level inference (60 min and more), overcoming all the other methods in terms of correlation between the measured and the predicted glucose signal and in terms of clinical outcome.INDEX TERMS Continuous glucose monitoring, diabetes, non-linear autoregressive neural network, long short-term memory (LSTM) network, time-series analysis, machine learning.

Although immunohistochemistry (IHC) is a popular imaging technique, the quantitative analysis of IHC images via computer-aided methods is an emerging field that is gaining more and more importance thanks to the new developments in digital high-throughput scanners. In this paper, we discuss the main steps of IHC and review the techniques for computer-aided chromogenic IHC analysis, including methods to determine the location of interest of the antigens and quantify their activations. Moreover, we discuss the issues arising from the standardization of the immunostaining process, that are generally overlooked by the current literature, and finally provide requirements for reliable computer-aided IHC quantification.

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Classifying HEp-2 fluorescence patterns in Indirect Immunofluorescence (IIF) HEp-2 cell imaging is important for the differential diagnosis of autoimmune diseases. The current technique, based on human visual inspection, is time-consuming, subjective and dependent on the operator's experience. Automating this process may be a solution to these limitations, making IIF faster and more reliable. This work proposes a classification approach based on Subclass Discriminant Analysis (SDA), a dimensionality reduction technique that provides an effective representation of the cells in the feature space, suitably coping with the high within-class variance typical of HEp-2 cell patterns. In order to generate an adequate characterization of the fluorescence patterns, we investigate the individual and combined contributions of several image attributes, showing that the integration of morphological, global and local textural features is the most suited for this purpose. The proposed approach provides an accuracy of the staining pattern classification of about 90%.

Motivation High-throughput next-generation sequencing can generate huge sequence files, whose analysis requires alignment algorithms that are typically very demanding in terms of memory and computational resources. This is a significant issue, especially for machines with limited hardware capabilities. As the redundancy of the sequences typically increases with coverage, collapsing such files into compact sets of non-redundant reads has the 2-fold advantage of reducing file size and speeding-up the alignment, avoiding to map the same sequence multiple times. Method BioSeqZip generates compact and sorted lists of alignment-ready non-redundant sequences, keeping track of their occurrences in the raw files as well as of their quality score information. By exploiting a memory-constrained external sorting algorithm, it can be executed on either single- or multi-sample datasets even on computers with medium computational capabilities. On request, it can even re-expand the compacted files to their original state. Results Our extensive experiments on RNA-Seq data show that BioSeqZip considerably brings down the computational costs of a standard sequence analysis pipeline, with particular benefits for the alignment procedures that typically have the highest requirements in terms of memory and execution time. In our tests, BioSeqZip was able to compact 2.7 billion of reads into 963 million of unique tags reducing the size of sequence files up to 70% and speeding-up the alignment by 50% at least. Availability and implementation BioSeqZip is available at https://github.com/bioinformatics-polito/BioSeqZip. Supplementary information Supplementary data are available at Bioinformatics online.

The automatization of the analysis of Indirect Immunofluorescence (IIF) images is of paramount importance for the diagnosis of autoimmune diseases. This paper proposes a solution to one of the most challenging steps of this process, the segmentation of HEp-2 cells, through an adaptive marker-controlled watershed approach. Our algorithm automatically conforms the marker selection pipeline to the peculiar characteristics of the input image, hence it is able to cope with different fluorescent intensities and staining patterns without any a priori knowledge. Furthermore, it shows a reduced sensitivity to over-segmentation errors and uneven illumination, that are typical issues of IIF imaging.