Late diagnosis and high costs are key factors that negatively impact the care of cancer patients worldwide. Although the availability of biological markers for the diagnosis of cancer type is increasing, costs and reliability of tests currently present a barrier to the adoption of their routine use. There is a pressing need for accurate methods that enable early diagnosis and cover a broad range of cancers. The use of machine learning and RNA-seq expression analysis has shown promise in the classification of cancer type. However, research is inconclusive about which type of machine learning models are optimal. The suitability of five algorithms were assessed for the classification of 17 different cancer types. Each algorithm was fine-tuned and trained on the full array of 18,015 genes per sample, for 4,221 samples (75 % of the dataset). They were then tested with 1,408 samples (25 % of the dataset) for which cancer types were withheld to determine the accuracy of prediction. The results show that ensemble algorithms achieve 100% accuracy in the classification of 14 out of 17 types of cancer. The clustering and classification models, while faster than the ensembles, performed poorly due to the high level of noise in the dataset. When the features were reduced to a list of 20 genes, the ensemble algorithms maintained an accuracy above 95% as opposed to the clustering and classification models.
Long non-coding RNAs (lncRNAs) are a class of non-coding RNAs which play a significant role in several biological processes. RNA-seq based transcriptome sequencing has been extensively used for identification of lncRNAs. However, accurate identification of lncRNAs in RNA-seq datasets is crucial for exploring their characteristic functions in the genome as most coding potential computation (CPC) tools fail to accurately identify them in transcriptomic data. Well-known CPC tools such as CPC2, lncScore, CPAT are primarily designed for prediction of lncRNAs based on the GENCODE, NONCODE and CANTAT…
In recent years, the advances in single-cell RNA-seq techniques have enabled us to perform large-scale transcriptomic profiling at single-cell resolution in a high-throughput manner. Unsupervised learning such as data clustering has become the central component to identify and characterize novel cell types and gene expression patterns. In this study, we review the existing single-cell RNA-seq data clustering methods with critical insights into the related advantages and limitations. In addition, we also review the upstream single-cell RNA-seq data processing techniques such as quality control,…
We propose a probabilistic model for interpreting gene expression levels that are observed through single-cell RNA sequencing. In the model, each cell has a low-dimensional latent representation. Additional latent variables account for technical effects that may erroneously set some observations of gene expression levels to zero. Conditional distributions are specified by neural networks, giving the proposed model enough flexibility to fit the data well. We use variational inference and stochastic optimization to approximate the posterior distribution. The inference procedure scales to over on…
Long non-coding RNA, microRNA, and messenger RNA enable key regulations of various biological processes through a variety of diverse interaction mechanisms. Identifying the interactions and cross-talk between these heterogeneous RNA classes is essential in order to uncover the functional role of individual RNA transcripts, especially for unannotated and newly-discovered RNA sequences with no known interactions. Recently, sequence-based deep learning and network embedding methods are becoming promising approaches that can either predict RNA-RNA interactions from a sequence or infer missing inte…
Ecole Polytechnique Fédérale de Lausanne（洛桑联邦理工学院）；Swiss Data Science Center（瑞士数据科学中心）；ETH Zürich（苏黎世联邦理工学院）
Classification algorithms using RNA-Sequencing (RNA-Seq) data as input are used in a variety of biological applications. By nature, RNA-Seq data is subject to uncontrolled fluctuations both within and especially across datasets, which presents a major difficulty for a trained classifier to generalize to an external dataset. Replacing raw gene counts with the rank of gene counts inside an observation has proven effective to mitigate this problem. However, the rank of a feature is by definition relative to all other features, including highly variable features that introduce noise in the ranking…
Single-cell RNA-seq foundation models achieve strong performance on downstream tasks but remain black boxes, limiting their utility for biological discovery. Recent work has shown that sparse dictionary learning can extract concepts from deep learning models, with promising applications in biomedical imaging and protein models. However, interpreting biological concepts remains challenging, as biological sequences are not inherently human-interpretable. We introduce a novel concept-based interpretability framework for single-cell RNA-seq models with a focus on concept interpretation and evaluat…
A Hierarchical Sheaf Spectral Embedding Framework for Single-Cell RNA-seq Analysis
Department of Mathematics, Michigan State University（密歇根州立大学数学系）；Department of Biochemistry and Molecular Biology, Michigan State University（密歇根州立大学生物化学与分子生物学系）；Department of Electrical and Computer Engineering, Michigan State University（密歇根州立大学电气与计算机工程系）
German Research Center for Artificial Intelligence (DFKI)（德国人工智能研究中心）；National University of Sciences and Technology（国家科技大学）
Functional or non-coding RNAs are attracting more attention as they are now potentially considered valuable resources in the development of new drugs intended to cure several human diseases. The identification of drugs targeting the regulatory circuits of functional RNAs depends on knowing its family, a task which is known as RNA sequence classification. State-of-the-art small noncoding RNA classification methodologies take secondary structural features as input. However, in such classification, feature extraction approaches only take global characteristics into account and completely oversigh…
University of Minnesota Twin Cities（明尼苏达大学双城分校）；Guangzhou Institutes of Biomedicine and Health, Chinese Academy of Sciences（中国科学院广州生物医药与健康研究院）；University of Kansas Medical Center（堪萨斯大学医学中心）
High-throughput mRNA sequencing (RNA-Seq) is widely used for transcript quantification of gene isoforms. Since RNA-Seq data alone is often not sufficient to accurately identify the read origins from the isoforms for quantification, we propose to explore protein domain-domain interactions as prior knowledge for integrative analysis with RNA-seq data. We introduce a Network-based method for RNA-Seq-based Transcript Quantification (Net-RSTQ) to integrate protein domain-domain interaction network with short read alignments for transcript abundance estimation. Based on our observation that the abun…
CovID-19 genetics analysis is critical to determine virus type,virus variant and evaluate vaccines. In this paper, SARS-Cov-2 RNA sequence analysis relative to region or territory is investigated. A uniform framework of sequence SVM model with various genetics length from short to long and mixed-bases is developed by projecting SARS-Cov-2 RNA sequence to different dimensional space, then scoring it according to the output probability of pre-trained SVM models to explore the territory or origin information of SARS-Cov-2. Different sample size ratio of training set and test set is also discussed…
