LSCS-Net: A lightweight skin cancer segmentation network with densely connected multi-rate atrous convolution.

The rising occurrence and notable public health consequences of skin cancer, especially of the most challenging form known as melanoma, have created an urgent demand for more advanced approaches to disease management. The integration of modern computer vision methods into clinical procedures offers the potential for enhancing the detection of skin cancer . The UNet model has gained prominence as a valuable tool for this objective, continuously evolving to tackle the difficulties associated with the inherent diversity of dermatological images. These challenges stem from diverse medical origins and are further complicated by variations in lighting, patient characteristics, and hair density. In this work, we present an innovative end-to-end trainable network crafted for the segmentation of skin cancer . This network comprises an encoder-decoder architecture, a novel feature extraction block, and a densely connected multi-rate Atrous convolution block. We evaluated the performance of the proposed lightweight skin cancer segmentation network (LSCS-Net) on three widely used benchmark datasets for skin lesion segmentation: ISIC 2016, ISIC 2017, and ISIC 2018. The generalization capabilities of LSCS-Net are testified by the excellent performance on breast cancer and thyroid nodule segmentation datasets. The empirical findings confirm that LSCS-net attains state-of-the-art results, as demonstrated by a significantly elevated Jaccard index.

Unveiling the future of breast cancer assessment: a critical review on generative adversarial networks in elastography ultrasound.

Elastography Ultrasound provides elasticity information of the tissues, which is crucial for understanding the density and texture, allowing for the diagnosis of different medical conditions such as fibrosis and cancer. In the current medical imaging scenario, elastograms for B-mode Ultrasound are restricted to well-equipped hospitals, making the modality unavailable for pocket ultrasound. To highlight the recent progress in elastogram synthesis, this article performs a critical review of generative adversarial network (GAN) methodology for elastogram generation from B-mode Ultrasound images. Along with a brief overview of cutting-edge medical image synthesis, the article highlights the contribution of the GAN framework in light of its impact and thoroughly analyzes the results to validate whether the existing challenges have been effectively addressed. Specifically, This article highlights that GANs can successfully generate accurate elastograms for deep-seated breast tumors (without having artifacts) and improve diagnostic effectiveness for pocket US. Furthermore, the results of the GAN framework are thoroughly analyzed by considering the quantitative metrics, visual evaluations, and cancer diagnostic accuracy. Finally, essential unaddressed challenges that lie at the intersection of elastography and GANs are presented, and a few future directions are shared for the elastogram synthesis research.

Toward a Universal Measure of Facial Difference Using Two Novel Machine Learning Models.

A sensitive, objective, and universally accepted method of measuring facial deformity does not currently exist. Two distinct machine learning methods are described here that produce numerical scores reflecting the level of deformity of a wide variety of facial conditions. METHODS: The first proposed technique utilizes an object detector based on a cascade function of Haar features. The model was trained using a dataset of 200,000 normal faces, as well as a collection of images devoid of faces. With the model trained to detect normal faces, the face detector confidence score was shown to function as a reliable gauge of facial abnormality. The second technique developed is based on a deep learning architecture of a convolutional autoencoder trained with the same rich dataset of normal faces. Because the convolutional autoencoder regenerates images disposed toward their training dataset (ie, normal faces), we utilized its reconstruction error as an indicator of facial abnormality. Scores generated by both methods were compared with human ratings obtained using a survey of 80 subjects evaluating 60 images depicting a range of facial deformities [rating from 1 (abnormal) to 7 (normal)]. RESULTS: The machine scores were highly correlated to the average human score, with overall Pearson's correlation coefficient exceeding 0.96 (P < 0.00001). Both methods were computationally efficient, reporting results within 3 seconds. CONCLUSIONS: These models show promise for adaptation into a clinically accessible handheld tool. It is anticipated that ongoing development of this technology will facilitate multicenter collaboration and comparison of outcomes between conditions, techniques, operators, and institutions.

Robust Recurrent CNV Detection in the Presence of Inter-Subject Variability.

The study of recurrent copy number variations (CNVs) plays an important role in understanding the onset and evolution of complex diseases such as cancer. Array-based comparative genomic hybridization (aCGH) is a widely used microarray based technology for identifying CNVs. However, due to high noise levels and inter-sample variability, detecting recurrent CNVs from aCGH data remains a challenging topic. This paper proposes a novel method for identification of the recurrent CNVs. In the proposed method, the noisy aCGH data is modeled as the superposition of three matrices: a full-rank matrix of weighted piece-wise generating signals accounting for the clean aCGH data, a Gaussian noise matrix to model the inherent experimentation errors and other sources of error, and a sparse matrix to capture the sparse inter-sample (sample-specific) variations. We demonstrated the ability of our method to separate accurately recurrent CNVs from sample-specific variations and noise in both simulated (artificial) data and real data. The proposed method produced more accurate results than current state-of-the-art methods used in recurrent CNV detection and exhibited robustness to noise and sample-specific variations.

Single-cell RNA sequencing of a European and an African lymphoblastoid cell line.

In biomedical research, lymphoblastoid cell lines (LCLs), often established by in vitro infection of resting B cells with Epstein-Barr virus, are commonly used as surrogates for peripheral blood lymphocytes. Genomic and transcriptomic information on LCLs has been used to study the impact of genetic variation on gene expression in humans. Here we present single-cell RNA sequencing (scRNA-seq) data on GM12878 and GM18502-two LCLs derived from the blood of female donors of European and African ancestry, respectively. Cells from three samples (the two LCLs and a 1:1 mixture of the two) were prepared separately using a 10x Genomics Chromium Controller and deeply sequenced. The final dataset contained 7,045 cells from GM12878, 5,189 from GM18502, and 5,820 from the mixture, offering valuable information on single-cell gene expression in highly homogenous cell populations. This dataset is a suitable reference for population differentiation in gene expression at the single-cell level. Data from the mixture provide additional valuable information facilitating the development of statistical methods for data normalization and batch effect correction.

CrossLink: a novel method for cross-condition classification of cancer subtypes.

BACKGROUND: We considered the prediction of cancer classes (e.g. subtypes) using patient gene expression profiles that contain both systematic and condition-specific biases when compared with the training reference dataset. The conventional normalization-based approaches cannot guarantee that the gene signatures in the reference and prediction datasets always have the same distribution for all different conditions as the class-specific gene signatures change with the condition. Therefore, the trained classifier would work well under one condition but not under another. METHODS: To address the problem of current normalization approaches, we propose a novel algorithm called CrossLink (CL). CL recognizes that there is no universal, condition-independent normalization mapping of signatures. In contrast, it exploits the fact that the signature is unique to its associated class under any condition and thus employs an unsupervised clustering algorithm to discover this unique signature. RESULTS: We assessed the performance of CL for cross-condition predictions of PAM50 subtypes of breast cancer by using a simulated dataset modeled after TCGA BRCA tumor samples with a cross-validation scheme, and datasets with known and unknown PAM50 classification. CL achieved prediction accuracy >73 %, highest among other methods we evaluated. We also applied the algorithm to a set of breast cancer tumors derived from Arabic population to assign a PAM50 classification to each tumor based on their gene expression profiles. CONCLUSIONS: A novel algorithm CrossLink for cross-condition prediction of cancer classes was proposed. In all test datasets, CL showed robust and consistent improvement in prediction performance over other state-of-the-art normalization and classification algorithms.

Estimating conditional probabilities for the detection of unfavorable copy number alterations in a targeted therapy.

Emerging targeted therapies have shown benefits such as less toxicity and higher effectiveness in specific types of cancer treatment; however, the accessibility of these advantages may rely on correct identification of suitable patients, which remains highly immature. We assume that copy number profiles, being accessible genomic data via microarray techniques, can provide useful information regarding drug response and shed light on personalized therapy. Based on the mechanism of action (MOA) of trastuzumab in the HER2 signaling pathway, a Bayesian network model in which copy number alterations (CNAs) serve as latent parents modifying signal transduction is applied. Two model parameters M-score and R -value which stand for the qualitative and quantitative effects of CNAs on drug effectiveness and are functions of conditional probabilities (CPs), are defined. An expectation-maximization (EM) algorithm is developed for estimating CPs, M-scores, and R-values from continuous measures, such as microarray data. We show through simulations that the EM algorithm can outperform classical threshold-based methods in the estimation of CPs and thereby provide improved performance for the detection of unfavorable CNAs. Several candidates of unfavorable CNAs to the trastuzumab therapy in breast cancer are provided in a real data example.

Reducing confounding and suppression effects in TCGA data: an integrated analysis of chemotherapy response in ovarian cancer.

BACKGROUND: Despite initial response in adjuvant chemotherapy, ovarian cancer patients treated with the combination of paclitaxel and carboplatin frequently suffer from recurrence after few cycles of treatment, and the underlying mechanisms causing the chemoresistance remain unclear. Recently, The Cancer Genome Atlas (TCGA) research network concluded an ovarian cancer study and released the dataset to the public. The TCGA dataset possesses large sample size, comprehensive molecular profiles, and clinical outcome information; however, because of the unknown molecular subtypes in ovarian cancer and the great diversity of adjuvant treatments TCGA patients went through, studying chemotherapeutic response using the TCGA data is difficult. Additionally, factors such as sample batches, patient ages, and tumor stages further confound or suppress the identification of relevant genes, and thus the biological functions and disease mechanisms. RESULTS: To address these issues, herein we propose an analysis procedure designed to reduce suppression effect by focusing on a specific chemotherapeutic treatment, and to remove confounding effects such as batch effect, patient's age, and tumor stages. The proposed procedure starts with a batch effect adjustment, followed by a rigorous sample selection process. Then, the gene expression, copy number, and methylation profiles from the TCGA ovarian cancer dataset are analyzed using a semi-supervised clustering method combined with a novel scoring function. As a result, two molecular classifications, one with poor copy number profiles and one with poor methylation profiles, enriched with unfavorable scores are identified. Compared with the samples enriched with favorable scores, these two classifications exhibit poor progression-free survival (PFS) and might be associated with poor chemotherapy response specifically to the combination of paclitaxel and carboplatin. Significant genes and biological processes are detected subsequently using classical statistical approaches and enrichment analysis. CONCLUSIONS: The proposed procedure for the reduction of confounding and suppression effects and the semi-supervised clustering method are essential steps to identify genes associated with the chemotherapeutic response.

Evaluating dynamic effects of copy number alterations on gene expression using a single transcription model.

DNA copy number alterations (CNAs) are known to be related to genetic diseases, including cancer. The unlimited transcription (UT) model, in which transcription occurs permissively with a simple activation probability, has been proposed to investigate long-term effects of CNAs on gene expression values. Queueing theory was applied, and the copy-number-gene-expression relationship has been shown to be generally nonlinear in the UT model. However, the dynamic effects of CNAs on transcription and the underlying disorders related to diseases remain greatly unknown. Since most genes in a single cell are permissively transcribed in short periods of time interspersed by long periods of limited transcription, an alternative model for transcription in the restrictive state is needed for unraveling the effects of CNAs on gene expression levels with time. To address these issues, herein a single transcription (ST) model is proposed, in which bound TFs are assumed to be unloaded immediately after stimulating a transcription. Using the Laplace-Stieltjes transform and numerical analysis, the relationship between DNA copy number and gene expression level is evaluated. Dynamic modeling reveals that CNAs would potentially alter, or even reverse, the burst-like gene expression modifications while shifting from the ST model to the UT model. Moreover, functional disorders in transcriptional oscillation due to CNAs are shown via simulation. This paper demonstrates how mathematical theories could be helpful to interpret statistical findings from real data and achieve a better understanding of cancer biology.

Inferring connectivity of genetic regulatory networks using information-theoretic criteria.

Recently, the concept of mutual information has been proposed for inferring the structure of genetic regulatory networks from gene expression profiling. After analyzing the limitations of mutual information in inferring the gene-to-gene interactions, this paper introduces the concept of conditional mutual information and based on it proposes two novel algorithms to infer the connectivity structure of genetic regulatory networks. One of the proposed algorithms exhibits a better accuracy while the other algorithm excels in simplicity and flexibility. By exploiting the mutual information and conditional mutual information, a practical metric is also proposed to assess the likeliness of direct connectivity between genes. This novel metric resolves a common limitation associated with the current inference algorithms, namely the situations where the gene connectivity is established in terms of the dichotomy of being either connected or disconnected. Based on the data sets generated by synthetic networks, the performance of the proposed algorithms is compared favorably relative to existing state-of-the-art schemes. The proposed algorithms are also applied on realistic biological measurements, such as the cutaneous melanoma data set, and biological meaningful results are inferred.