Biomarker Identification through Multiomics Data Analysis of Prostate Cancer Prognostication Using a Deep Learning Model and Similarity Network Fusion.
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ABSTRACT:
SUBMITTER: Wang TH
PROVIDER: S-EPMC8196729 | biostudies-literature |
REPOSITORIES: biostudies-literature
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Project description:In this article, the authors aim to maximally utilize multimodality neuroimaging and genetic data for identifying Alzheimer's disease (AD) and its prodromal status, Mild Cognitive Impairment (MCI), from normal aging subjects. Multimodality neuroimaging data such as MRI and PET provide valuable insights into brain abnormalities, while genetic data such as single nucleotide polymorphism (SNP) provide information about a patient's AD risk factors. When these data are used together, the accuracy of AD diagnosis may be improved. However, these data are heterogeneous (e.g., with different data distributions), and have different number of samples (e.g., with far less number of PET samples than the number of MRI or SNPs). Thus, learning an effective model using these data is challenging. To this end, we present a novel three-stage deep feature learning and fusion framework, where deep neural network is trained stage-wise. Each stage of the network learns feature representations for different combinations of modalities, via effective training using the maximum number of available samples. Specifically, in the first stage, we learn latent representations (i.e., high-level features) for each modality independently, so that the heterogeneity among modalities can be partially addressed, and high-level features from different modalities can be combined in the next stage. In the second stage, we learn joint latent features for each pair of modality combination by using the high-level features learned from the first stage. In the third stage, we learn the diagnostic labels by fusing the learned joint latent features from the second stage. To further increase the number of samples during training, we also use data at multiple scanning time points for each training subject in the dataset. We evaluate the proposed framework using Alzheimer's disease neuroimaging initiative (ADNI) dataset for AD diagnosis, and the experimental results show that the proposed framework outperforms other state-of-the-art methods.
| S-EPMC6865441 | biostudies-literature
Project description:The biomarker networks measured by different modalities of data (e.g., structural magnetic resonance imaging (sMRI), diffusion tensor imaging (DTI)) may share the same true underlying biological model. In this work, we propose a node-wise biomarker graphical model to leverage the shared mechanism between multi-modality data to provide a more reliable estimation of the target modality network and account for the heterogeneity in networks due to differences between subjects and networks of external modality. Latent variables are introduced to represent the shared unobserved biological network and the information from the external modality is incorporated to model the distribution of the underlying biological network. We propose an efficient approximation to the posterior expectation of the latent variables that reduces computational cost by at least 50%. The performance of the proposed method is demonstrated by extensive simulation studies and an application to construct gray matter brain atrophy network of Huntington's disease by using sMRI data and DTI data. The identified network connections are more consistent with clinical literature and better improve prediction in follow-up clinical outcomes and separate subjects into clinically meaningful subgroups with different prognosis than alternative methods.
| S-EPMC8329868 | biostudies-literature
Project description:Historically, the database search algorithms have been the de facto standard for inferring peptides from mass spectrometry (MS) data. Database search algorithms deduce peptides by transforming theoretical peptides into theoretical spectra and matching them to the experimental spectra. Heuristic similarity-scoring functions are used to match an experimental spectrum to a theoretical spectrum. However, the heuristic nature of the scoring functions and the simple transformation of the peptides into theoretical spectra, along with noisy mass spectra for the less abundant peptides, can introduce a cascade of inaccuracies. In this paper, we design and implement a Deep Cross-Modal Similarity Network called SpeCollate, which overcomes these inaccuracies by learning the similarity function between experimental spectra and peptides directly from the labeled MS data. SpeCollate transforms spectra and peptides into a shared Euclidean subspace by learning fixed size embeddings for both. Our proposed deep-learning network trains on sextuplets of positive and negative examples coupled with our custom-designed SNAP-loss function. Online hardest negative mining is used to select the appropriate negative examples for optimal training performance. We use 4.8 million sextuplets obtained from the NIST and MassIVE peptide libraries to train the network and demonstrate that for closed search, SpeCollate is able to perform better than Crux and MSFragger in terms of the number of peptide-spectrum matches (PSMs) and unique peptides identified under 1% FDR for real-world data. SpeCollate also identifies a large number of peptides not reported by either Crux or MSFragger. To the best of our knowledge, our proposed SpeCollate is the first deep-learning network that can determine the cross-modal similarity between peptides and mass-spectra for MS-based proteomics. We believe SpeCollate is significant progress towards developing machine-learning solutions for MS-based omics data analysis. SpeCollate is available at https://deepspecs.github.io/.
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Project description:MethodsPatients (363 in total) with stomach adenocarcinoma from The Cancer Genome Atlas (TCGA) cohort were included. An autoencoder was constructed to integrate the RNA sequencing, miRNA sequencing, and methylation data. The features of the bottleneck layer were used to perform the k-means clustering algorithm to obtain different subgroups for evaluating the prognosis-related risk of stomach adenocarcinoma. The model's robustness was verified using a 10-fold cross-validation (CV). Survival was analyzed by the Kaplan-Meier method. Univariate and multivariate Cox regression was used to estimate hazard risk. The model was validated in three independent cohorts with different endpoints.ResultsThe patients were divided into low-risk and high-risk groups according to the k-means clustering algorithm. The high-risk group had a significantly higher risk of poor survival (log-rank P value = 2.80e - 06; adjusted hazard ratio = 2.386, 95% confidence interval: 1.607~3.543), a concordance index (C-index) of 0.714, and a Brier score of 0.184. The model performed well both in the 10-fold CV procedure and three independent cohorts from the Gene Expression Omnibus (GEO) repository.ConclusionsA robust and generalizable model based on the autoencoder was proposed to integrate multiomics data and predict the prognosis of patients with stomach adenocarcinoma. The model demonstrates better performance than two alternative approaches on prognosis prediction. The results might provide the grounds for further exploring the potential biomarkers to predict the prognosis of patients with stomach adenocarcinoma.
| S-EPMC9633210 | biostudies-literature
Project description:Malignant brain tumors pose a substantial burden on morbidity and mortality. As clinical data collection improves, along with the capacity to analyze it, novel predictive clinical tools may improve prognosis prediction. Deep learning (DL) holds promise for integrating clinical data of various modalities. A systematic review of the DL-based prognostication of gliomas was performed using the Embase (Elsevier), PubMed MEDLINE (National library of Medicine), and Scopus (Elsevier) databases, in accordance with PRISMA guidelines. All included studies focused on the prognostication of gliomas, and predicted overall survival (13 studies, 81%), overall survival as well as genotype (2 studies, 12.5%), and response to immunotherapy (1 study, 6.2%). Multimodal analyses were varied, with 6 studies (37.5%) combining MRI with clinical data; 6 studies (37.5%) integrating MRI with histologic, clinical, and biomarker data; 3 studies (18.8%) combining MRI with genomic data; and 1 study (6.2%) combining histologic imaging with clinical data. Studies that compared multimodal models to unimodal-only models demonstrated improved predictive performance. The risk of bias was mixed, most commonly due to inconsistent methodological reporting. Overall, the use of multimodal data in DL assessments of gliomas leads to a more accurate overall survival prediction. However, due to data limitations and a lack of transparency in model and code reporting, the full extent of multimodal DL as a resource for brain tumor patients has not yet been realized.
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Project description:MOTIVATION:Recent technology developments have made it possible to generate various kinds of omics data, which provides opportunities to better solve problems such as disease subtyping or disease mapping using more comprehensive omics data jointly. Among many developed data-integration methods, the similarity network fusion (SNF) method has shown a great potential to identify new disease subtypes through separating similar subjects using multi-omics data. SNF effectively fuses similarity networks with pairwise patient similarity measures from different types of omics data into one fused network using both shared and complementary information across multiple types of omics data. RESULTS:In this article, we proposed an association-signal-annotation boosted similarity network fusion (ab-SNF) method, adding feature-level association signal annotations as weights aiming to up-weight signal features and down-weight noise features when constructing subject similarity networks to boost the performance in disease subtyping. In various simulation studies, the proposed ab-SNF outperforms the original SNF approach without weights. Most importantly, the improvement in the subtyping performance due to association-signal-annotation weights is amplified in the integration process. Applications to somatic mutation data, DNA methylation data and gene expression data of three cancer types from The Cancer Genome Atlas project suggest that the proposed ab-SNF method consistently identifies new subtypes in each cancer that more accurately predict patient survival and are more biologically meaningful. AVAILABILITY AND IMPLEMENTATION:The R package abSNF is freely available for downloading from https://github.com/pfruan/abSNF. SUPPLEMENTARY INFORMATION:Supplementary data are available at Bioinformatics online.
| S-EPMC6761966 | biostudies-literature
Project description:BACKGROUND:Non-small-cell lung cancer (NSCLC) patients often demonstrate varying clinical courses and outcomes, even within the same tumor stage. This study explores deep learning applications in medical imaging allowing for the automated quantification of radiographic characteristics and potentially improving patient stratification. METHODS AND FINDINGS:We performed an integrative analysis on 7 independent datasets across 5 institutions totaling 1,194 NSCLC patients (age median = 68.3 years [range 32.5-93.3], survival median = 1.7 years [range 0.0-11.7]). Using external validation in computed tomography (CT) data, we identified prognostic signatures using a 3D convolutional neural network (CNN) for patients treated with radiotherapy (n = 771, age median = 68.0 years [range 32.5-93.3], survival median = 1.3 years [range 0.0-11.7]). We then employed a transfer learning approach to achieve the same for surgery patients (n = 391, age median = 69.1 years [range 37.2-88.0], survival median = 3.1 years [range 0.0-8.8]). We found that the CNN predictions were significantly associated with 2-year overall survival from the start of respective treatment for radiotherapy (area under the receiver operating characteristic curve [AUC] = 0.70 [95% CI 0.63-0.78], p < 0.001) and surgery (AUC = 0.71 [95% CI 0.60-0.82], p < 0.001) patients. The CNN was also able to significantly stratify patients into low and high mortality risk groups in both the radiotherapy (p < 0.001) and surgery (p = 0.03) datasets. Additionally, the CNN was found to significantly outperform random forest models built on clinical parameters-including age, sex, and tumor node metastasis stage-as well as demonstrate high robustness against test-retest (intraclass correlation coefficient = 0.91) and inter-reader (Spearman's rank-order correlation = 0.88) variations. To gain a better understanding of the characteristics captured by the CNN, we identified regions with the most contribution towards predictions and highlighted the importance of tumor-surrounding tissue in patient stratification. We also present preliminary findings on the biological basis of the captured phenotypes as being linked to cell cycle and transcriptional processes. Limitations include the retrospective nature of this study as well as the opaque black box nature of deep learning networks. CONCLUSIONS:Our results provide evidence that deep learning networks may be used for mortality risk stratification based on standard-of-care CT images from NSCLC patients. This evidence motivates future research into better deciphering the clinical and biological basis of deep learning networks as well as validation in prospective data.
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Project description:The use of deep learning models in computational biology has increased massively in recent years, and it is expected to continue with the current advances in the fields such as Natural Language Processing. These models, although able to draw complex relations between input and target, are also inclined to learn noisy deviations from the pool of data used during their development. In order to assess their performance on unseen data (their capacity to generalize), it is common to split the available data randomly into development (train/validation) and test sets. This procedure, although standard, has been shown to produce dubious assessments of generalization due to the existing similarity between samples in the databases used. In this work, we present SpanSeq, a database partition method for machine learning that can scale to most biological sequences (genes, proteins and genomes) in order to avoid data leakage between sets. We also explore the effect of not restraining similarity between sets by reproducing the development of two state-of-the-art models on bioinformatics, not only confirming the consequences of randomly splitting databases on the model assessment, but expanding those repercussions to the model development. SpanSeq is available at https://github.com/genomicepidemiology/SpanSeq.
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Project description:Fingerprint biometrics are integral to digital authentication and forensic science. However, they are based on the unproven assumption that no two fingerprints, even from different fingers of the same person, are alike. This renders them useless in scenarios where the presented fingerprints are from different fingers than those on record. Contrary to this prevailing assumption, we show above 99.99% confidence that fingerprints from different fingers of the same person share very strong similarities. Using deep twin neural networks to extract fingerprint representation vectors, we find that these similarities hold across all pairs of fingers within the same person, even when controlling for spurious factors like sensor modality. We also find evidence that ridge orientation, especially near the fingerprint center, explains a substantial part of this similarity, whereas minutiae used in traditional methods are almost nonpredictive. Our experiments suggest that, in some situations, this relationship can increase forensic investigation efficiency by almost two orders of magnitude.
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Project description:Understanding how the brain learns throughout a lifetime remains a long-standing challenge. In artificial neural networks (ANNs), incorporating novel information too rapidly results in catastrophic interference, i.e., abrupt loss of previously acquired knowledge. Complementary Learning Systems Theory (CLST) suggests that new memories can be gradually integrated into the neocortex by interleaving new memories with existing knowledge. This approach, however, has been assumed to require interleaving all existing knowledge every time something new is learned, which is implausible because it is time-consuming and requires a large amount of data. We show that deep, nonlinear ANNs can learn new information by interleaving only a subset of old items that share substantial representational similarity with the new information. By using such similarity-weighted interleaved learning (SWIL), ANNs can learn new information rapidly with a similar accuracy level and minimal interference, while using a much smaller number of old items presented per epoch (fast and data-efficient). SWIL is shown to work with various standard classification datasets (Fashion-MNIST, CIFAR10, and CIFAR100), deep neural network architectures, and in sequential learning frameworks. We show that data efficiency and speedup in learning new items are increased roughly proportionally to the number of nonoverlapping classes stored in the network, which implies an enormous possible speedup in human brains, which encode a high number of separate categories. Finally, we propose a theoretical model of how SWIL might be implemented in the brain.
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