Dataset Information

GraphDDP: a graph-embedding approach to detect differentiation pathways in single-cell-data using prior class knowledge.

ABSTRACT: Cell types can be characterized by expression profiles derived from single-cell RNA-seq. Subpopulations are identified via clustering, yielding intuitive outcomes that can be validated by marker genes. Clustering, however, implies a discretization that cannot capture the continuous nature of differentiation processes. One could give up the detection of subpopulations and directly estimate the differentiation process from cell profiles. A combination of both types of information, however, is preferable. Crucially, clusters can serve as anchor points of differentiation trajectories. Here we present GraphDDP, which integrates both viewpoints in an intuitive visualization. GraphDDP starts from a user-defined cluster assignment and then uses a force-based graph layout approach on two types of carefully constructed edges: one emphasizing cluster membership, the other, based on density gradients, emphasizing differentiation trajectories. We show on intestinal epithelial cells and myeloid progenitor data that GraphDDP allows the identification of differentiation pathways that cannot be easily detected by other approaches.

SUBMITTER: Costa F

PROVIDER: S-EPMC6134144 | biostudies-literature | 2018 Sep

REPOSITORIES: biostudies-literature

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GraphDDP: a graph-embedding approach to detect differentiation pathways in single-cell-data using prior class knowledge.

Costa Fabrizio F Grün Dominic D Backofen Rolf R

Nature communications 20180911 1

Cell types can be characterized by expression profiles derived from single-cell RNA-seq. Subpopulations are identified via clustering, yielding intuitive outcomes that can be validated by marker genes. Clustering, however, implies a discretization that cannot capture the continuous nature of differentiation processes. One could give up the detection of subpopulations and directly estimate the differentiation process from cell profiles. A combination of both types of information, however, is pref ...[more]

PMID: 30206223

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Project description:BackgroundThe pharmaceutical field faces a significant challenge in validating drug target interactions (DTIs) due to the time and cost involved, leading to only a fraction being experimentally verified. To expedite drug discovery, accurate computational methods are essential for predicting potential interactions. Recently, machine learning techniques, particularly graph-based methods, have gained prominence. These methods utilize networks of drugs and targets, employing knowledge graph embedding (KGE) to represent structured information from knowledge graphs in a continuous vector space. This phenomenon highlights the growing inclination to utilize graph topologies as a means to improve the precision of predicting DTIs, hence addressing the pressing requirement for effective computational methodologies in the field of drug discovery.ResultsThe present study presents a novel approach called DTIOG for the prediction of DTIs. The methodology employed in this study involves the utilization of a KGE strategy, together with the incorporation of contextual information obtained from protein sequences. More specifically, the study makes use of Protein Bidirectional Encoder Representations from Transformers (ProtBERT) for this purpose. DTIOG utilizes a two-step process to compute embedding vectors using KGE techniques. Additionally, it employs ProtBERT to determine target-target similarity. Different similarity measures, such as Cosine similarity or Euclidean distance, are utilized in the prediction procedure. In addition to the contextual embedding, the proposed unique approach incorporates local representations obtained from the Simplified Molecular Input Line Entry Specification (SMILES) of drugs and the amino acid sequences of protein targets.ConclusionsThe effectiveness of the proposed approach was assessed through extensive experimentation on datasets pertaining to Enzymes, Ion Channels, and G-protein-coupled Receptors. The remarkable efficacy of DTIOG was showcased through the utilization of diverse similarity measures in order to calculate the similarities between drugs and targets. The combination of these factors, along with the incorporation of various classifiers, enabled the model to outperform existing algorithms in its ability to predict DTIs. The consistent observation of this advantage across all datasets underlines the robustness and accuracy of DTIOG in the domain of DTIs. Additionally, our case study suggests that the DTIOG can serve as a valuable tool for discovering new DTIs.

Project description:Advances in machine learning and deep learning methods, together with the increasing availability of large-scale pharmacological, genomic, and chemical datasets, have created opportunities for identifying potentially useful relationships within biochemical networks. Knowledge embedding models have been found to have value in detecting knowledge-based correlations among entities, but little effort has been made to apply them to networks of biochemical entities. This is because such networks tend to be unbalanced and sparse, and knowledge embedding models do not work well on them. However, to some extent, the shortcomings of knowledge embedding models can be compensated for if they are used in association with graph embedding. In this paper, we combine knowledge embedding and graph embedding to represent biochemical entities and their relations as dense and low-dimensional vectors. We build a cascade learning framework which incorporates semantic features from the knowledge embedding model, and graph features from the graph embedding model, to score the probability of linking. The proposed method performs noticeably better than the models with which it is compared. It predicted links and entities with an accuracy of 93%, and its average hits@10 score has an average of 8.6% absolute improvement compared with original knowledge embedding model, 1.1% to 9.7% absolute improvement compared with other knowledge and graph embedding algorithm. In addition, we designed a meta-path algorithm to detect path relations in the biomedical network. Case studies further verify the value of the proposed model in finding potential relationships between diseases, drugs, genes, treatments, etc. Amongst the findings of the proposed model are the suggestion that VDR (vitamin D receptor) may be linked to prostate cancer. This is backed by evidence from medical databases and published research, supporting the suggestion that our proposed model could be of value to biomedical researchers.

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Dataset Information

GraphDDP: a graph-embedding approach to detect differentiation pathways in single-cell-data using prior class knowledge.

Publications

GraphDDP: a graph-embedding approach to detect differentiation pathways in single-cell-data using prior class knowledge.

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