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DataModel/Project/Core/Project-core-definition.yaml

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+Project-core:
+  description: Describes the core details of the project like project ID, summary,
+    overall design, publication related details and any other supplementary links
+    associated with the project
+  properties:
+    properties:
+      project_id:
+        description: Primary key or unique identified for a project
+        type: string
+        pattern: "^DO-[0-9]{4}$"
+        example: "P034"
+      summary:
+        description: Summary of the experiment from which the project has been derived
+        type: string
+        example: "The identification of novel therapeutic strategies to overcome
+            the intrinsic or acquired resistance to trametinib in mutant KRAS lung
+            adenocarcinoma (LUAD) is a major challenge. This study analyzes the effects
+            of trametinib in Id1, a key factor involved in the oncogenic KRAS pathway,
+            and investigates the Id1 role in acquire resistance and synergy with immunotherapy
+            in KRAS-driven LUAD. Restoring the antitumor immune response by blocking
+            programmed-cell death protein 1 (PD-1) and programmed-cell death-ligand
+            1 (PD-L1) pathway represents a major breakthrough in non-small-cell lung
+            cancer (NSCLC) treatment. Nevertheless, a high proportion of LUAD patients
+            with KRAS alterations remain refractory to this therapy. Material and
+            Methods: To explore whether MEK1/2 inhibition reduces Id1 expression,
+            in vitro and in vivo experiments were conducted in KRAS-mutant NSCLC cells
+            and murine models. RNAseq analysis was performed to elucidate the pathways
+            involved in Id1 inhibition. Apoptosis and PD-L1 expression was measured
+            by flow cytometry. Synergy of trametinib combined with anti-PD1 was investigated
+            in KRAS-mutant LUAD mouse models. Results: Using preclinical syngeneic
+            KRAS-mutant lung cancer mouse models, we demonstrate that trametinib synergizes
+            with PD-1 blockade to reduce lung cancer progression and increase mice
+            overall survival. This antitumor activity was linked to the degradation
+            of Id1 via proteasome, and an enhanced INF-Y-mediated PD-L1 tumor cell
+            expression in KRAS-mutant tumor cells. This effect required CD8+ T cells,
+            boosted the intratumoral CD8+/Treg ratio, reducing the intratumoral Treg/CD4+
+            ratio. Conclusions: Our data may support the role of Id1 in the trametinib
+            antitumoral effect, sustaining the mitogen-activated protein kinases (MAPK)
+            signaling pathway involved in the trametinib acquired resistance cells
+            and sensitizing KRAS-mutant lung tumors to PD-1 inhibitors, through PD-L1
+            overexpression."
+      overall_design:
+        description: Overall design of the experiment as given by the author
+        type: string
+        example: "In order to investigate the molecular mechanisms involved in the
+            trametinib-mediated Id1 downregulation, a global transcriptomic profiling
+            using RNA sequencing analysis was performed on murine CMT167 and KLA lung
+            cancer cells treated or not with trametinib"
+      donor_derived_dataset:
+        description: Whether the dataset has been derived from a donor or not
+        type: boolean
+        enum:
+        - True
+        - False
+        - NA
+        ontology_link:
+          type: string
+          description: Link to the ontology file
+          url: https://bioportal.bioontology.org/ontologies/HRAVS?p=classes&conceptid=https%3A%2F%2Fpurl.humanatlas.io%2Fvocab%2Fhravs%23HRAVS_1002101
+      organism:
+        description: The organism from which the samples were derived
+        type: string
+        example: "Homo sapiens"
+        ontology_link:
+          type: string
+          description: Link to the ontology file
+          url: https://bioportal.bioontology.org/ontologies/ORTH?p=classes&conceptid=http%3A%2F%2Fpurl.org%2Fnet%2Forth%23Organism
+      cell_line:
+        description: Identifier of the cell lines from which the samples were derived for this experiment
+        type: string
+        pattern: "^CVCL_[0-9]{4}$"
+        example: "CVCL_0030"
+        ontology_link:
+          type: string
+          description: Link to the ontology file
+          url: https://www.cellosaurus.org/index.html
+      author_cell_type:
+        description: Cell types as curated from the publication/source for this experiment
+        type: string
+        example: "CMT167 cell"
+        ontology_link:
+          type: string
+          description: Link to the ontology file
+          url: https://bioportal.bioontology.org/ontologies/CCF?p=classes&conceptid=http%3A%2F%2Fpurl.org%2Fccf%2FCellType
+      source_link:
+        description: Link to source from where the data was fetched given as a url
+        type: string
+        format: alphanumeric
+        example: https://www.ncbi.nlm.nih.gov/geo/query/acc.cgi?acc=GSE236258
+      supplementary_links:
+        description: External link(s) pointing to code, supplementary data files,
+          or analysis files associated with the project which will not be uploaded
+        type: array
+        format: alphanumeric
+        example: https://github.com/czbiohub/tabula-muris, http://celltag.org/
+  type: object
+  version: 1.0.0