Topic
Phenotype
About: Phenotype is a research topic. Over the lifetime, 5835 publications have been published within this topic receiving 283602 citations. The topic is also known as: fenotipica & phenotypical outcome.
Papers published on a yearly basis
1 / 2
Papers
TL;DR: An extensive catalog of genes that act in a migrating cell is provided, unique molecular functions involved in nematode cell migration are identified, and similar functions in humans are suggested.
Abstract: In both metazoan development and metastatic cancer, migrating cells must carry out a detailed, complex program of sensing cues, binding substrates, and moving their cytoskeletons. The linker cell in Caenorhabditis elegans males undergoes a stereotyped migration that guides gonad organogenesis, occurs with precise timing, and requires the nuclear hormone receptor NHR-67. To better understand how this occurs, we performed RNA-seq of individually staged and dissected linker cells, comparing transcriptomes from linker cells of third-stage (L3) larvae, fourth-stage (L4) larvae, and nhr-67-RNAi–treated L4 larvae. We observed expression of 8,000–10,000 genes in the linker cell, 22–25% of which were up- or down-regulated 20-fold during development by NHR-67. Of genes that we tested by RNAi, 22% (45 of 204) were required for normal shape and migration, suggesting that many NHR-67–dependent, linker cell-enriched genes play roles in this migration. One unexpected class of genes up-regulated by NHR-67 was tandem pore potassium channels, which are required for normal linker-cell migration. We also found phenotypes for genes with human orthologs but no previously described migratory function. Our results provide an extensive catalog of genes that act in a migrating cell, identify unique molecular functions involved in nematode cell migration, and suggest similar functions in humans.
7,186 citations
TL;DR: The utility of CIBERSORTx is evaluated in multiple tumor types, including melanoma, where single-cell reference profiles were used to dissect bulk clinical specimens, revealing cell-type-specific phenotypic states linked to distinct driver mutations and response to immune checkpoint blockade.
Abstract: Single-cell RNA-sequencing has emerged as a powerful technique for characterizing cellular heterogeneity, but it is currently impractical on large sample cohorts and cannot be applied to fixed specimens collected as part of routine clinical care. We previously developed an approach for digital cytometry, called CIBERSORT, that enables estimation of cell type abundances from bulk tissue transcriptomes. We now introduce CIBERSORTx, a machine learning method that extends this framework to infer cell-type-specific gene expression profiles without physical cell isolation. By minimizing platform-specific variation, CIBERSORTx also allows the use of single-cell RNA-sequencing data for large-scale tissue dissection. We evaluated the utility of CIBERSORTx in multiple tumor types, including melanoma, where single-cell reference profiles were used to dissect bulk clinical specimens, revealing cell-type-specific phenotypic states linked to distinct driver mutations and response to immune checkpoint blockade. We anticipate that digital cytometry will augment single-cell profiling efforts, enabling cost-effective, high-throughput tissue characterization without the need for antibodies, disaggregation or viable cells. CIBERSORTx, a suite of computational tools, enables inference of cell type abundance and cell-type-specific gene expression profiles from bulk RNA profiles.
3,625 citations
TL;DR: Owing to the importance of these tumour-associated phenotypes in metastasis and cancer-related mortality, targeting the products of such cellular plasticity is an attractive but challenging approach that is likely to lead to improved clinical management of cancer patients.
Abstract: Transitions between epithelial and mesenchymal states have crucial roles in embryonic development. Emerging data suggest a role for these processes in regulating cellular plasticity in normal adult tissues and in tumours, where they can generate multiple, distinct cellular subpopulations contributing to intratumoural heterogeneity. Some of these subpopulations may exhibit more differentiated features, whereas others have characteristics of stem cells. Owing to the importance of these tumour-associated phenotypes in metastasis and cancer-related mortality, targeting the products of such cellular plasticity is an attractive but challenging approach that is likely to lead to improved clinical management of cancer patients.
3,451 citations
TL;DR: This paper found that essential human genes are likely to encode hub proteins and are expressed widely in most tissues, while the vast majority of disease genes are non-essential and show no tendency to encoding hub proteins, and their expression pattern indicates that they are localized in the functional periphery of the network.
Abstract: A network of disorders and disease genes linked by known disorder-gene associations offers a platform to explore in a single graph-theoretic framework all known phenotype and disease gene associations, indicating the common genetic origin of many diseases. Genes associated with similar disorders show both higher likelihood of physical interactions between their products and higher expression profiling similarity for their transcripts, supporting the existence of distinct disease-specific functional modules. We find that essential human genes are likely to encode hub proteins and are expressed widely in most tissues. This suggests that disease genes also would play a central role in the human interactome. In contrast, we find that the vast majority of disease genes are nonessential and show no tendency to encode hub proteins, and their expression pattern indicates that they are localized in the functional periphery of the network. A selection-based model explains the observed difference between essential and disease genes and also suggests that diseases caused by somatic mutations should not be peripheral, a prediction we confirm for cancer genes.
3,151 citations
TL;DR: Mutational and epigenetic profiling of a large acute myeloid leukemia (AML) patient cohort revealed that IDH1/2-mutant AMLs display global DNA hypermethylation and a specificHypermethylation signature, suggesting a shared proleukemogenic effect.
2,780 citations
Related Topics (5)
Performance Metrics
| Year | Papers |
|---|---|
| 2026 | 23 |
| 2025 | 3,743 |
| 2024 | 6,969 |
| 2023 | 11,068 |
| 2022 | 10,115 |
| 2021 | 1,140 |