# Spaceflight Transcriptomics Analysis: OSD-244 Rodent Research-6

👤 **User**
`@spoke-genelab`: describe the Assay node and its relationships

---

🧠 **Assistant**

Here's a breakdown of the **Assay** node in the `spoke-genelab` knowledge graph, which represents individual experimental assay instances from NASA's Open Science Data Repository (OSDR).

### The Assay Node

**Identity:** The `Assay` node is typed as `OBI:0000070` and represents a unique experimental assay instance from NASA's OSDR.

```mermaid
graph LR
    S[Study] -->|PERFORMED_SpAS| A[Assay<br/>OBI:0000070]
    A -->|INVESTIGATED_ASiA| AN[Anatomy<br/>UBERON]
    A -->|INVESTIGATED_ASiCT| CT[CellType<br/>CL ontology]
    A -->|MEASURED_DIFFERENTIAL_EXPRESSION_ASmMG ★| G[Gene<br/>ENTREZ id]
    A -->|MEASURED_DIFFERENTIAL_ABUNDANCE_ASmO ★| O[Organism<br/>microbial taxonomy]
    A -->|MEASURED_DIFFERENTIAL_METHYLATION_ASmMR ★| MR[MethylationRegion<br/>1 kb genomic region]

    style A fill:#7F77DD,color:#fff
    style S fill:#378ADD,color:#fff
    style AN fill:#1D9E75,color:#fff
    style CT fill:#1D9E75,color:#fff
    style G fill:#BA7517,color:#fff
    style O fill:#993C1D,color:#fff
    style MR fill:#534AB7,color:#fff
```
> ★ = edge carries statistical properties (log₂FC, adj_p_value, group_mean_1/2, group_stdev_1/2)

### Incoming Relationship

| Predicate | From | Description |
|---|---|---|
| `PERFORMED_SpAS` | Study | A `Study` performed this `Assay` — the parent-child link |

### Outgoing Relationships

| Predicate | To | Edge properties? |
|---|---|---|
| `INVESTIGATED_ASiA` | Anatomy | No — links to UBERON anatomical entity |
| `INVESTIGATED_ASiCT` | CellType | No — links to Cell Ontology (CL) cell type |
| `MEASURED_DIFFERENTIAL_EXPRESSION_ASmMG` | Gene | **Yes** — `log2fc`, `adj_p_value`, `group_mean_1/2`, `group_stdev_1/2` |
| `MEASURED_DIFFERENTIAL_ABUNDANCE_ASmO` | Organism | **Yes** — `log2fc`, `lnfc`, `adj_p_value`, `q_value`, group means/stdevs |
| `MEASURED_DIFFERENTIAL_METHYLATION_ASmMR` | MethylationRegion | **Yes** — `methylation_diff`, `q_value`, group means/stdevs |

### Assay Node Properties

- `measurement` — type of data produced (e.g., transcriptomics, methylation, metagenomics)
- `technology` — platform or method (e.g., RNA-Seq, mass spec)
- `factors_1` / `factors_2` — primary and secondary experimental factors (independent variables)
- `factor_space_1` / `factor_space_2` — whether each group was Space Flight or a ground control condition
- `material_1/2`, `material_id_1/2`, `material_name_1/2` — biological material per group with UBERON codes

In short, the `Assay` node is the central analytical hub: it ties experimental context (study, tissue, cell type) to quantitative results (differential gene expression, microbial abundance shifts, and methylation changes), all carrying statistical properties on the edges.

---

👤 **User**
`@spoke-genelab`: Get information about study OSD-244

---

🧠 **Assistant**

Here is a summary of what the graph contains for **OSD-244**:

### Study: OSD-244 — Rodent Research-6

**Project type:** Spaceflight Study

### Assays

The study contains a **single RNA-Seq assay type** across many pairwise comparisons, all profiling **thymus** of rodents using **transcription profiling via RNA Sequencing (RNA-Seq)**.

There are **20 distinct assay nodes** representing pairwise differential expression comparisons. The raw result count (480) reflects the full Cartesian product of factor combinations stored in the graph.

#### Experimental design

The study compares groups across two dimensions:

**Space flight condition** — three groups appear as `factor_space`:
- **Space Flight** (animals on the ISS)
- **Ground Control** (matched Earth controls)
- **Basal Control** (vivarium/unmanipulated controls)

**Time points / other factors** in `factors_1` / `factors_2`:
- `~30 day`, `~60 day` (mission duration groups)
- `1 day` (early post-flight)
- `Upon euthanasia`, `Carcass`, `On Earth`, `On ISS` (sample collection conditions)

The 20 assay nodes represent pairwise comparisons across these conditions. All assays examined **thymus** tissue in both groups.

```mermaid
graph TD
    OSD244["OSD-244<br/>Rodent Research-6<br/>Spaceflight Study"]
    OSD244 --> A1["Assay: SF vs. GC<br/>~30 day"]
    OSD244 --> A2["Assay: SF vs. GC<br/>~60 day"]
    OSD244 --> A3["Assay: SF vs. BC<br/>~30 day"]
    OSD244 --> A4["Assay: SF vs. BC<br/>~60 day"]
    OSD244 --> A5["Assay: GC vs. BC<br/>~30 day"]
    OSD244 --> A6["Assay: GC vs. BC<br/>~60 day"]
    OSD244 --> A7["Cross-time<br/>comparisons..."]

    A1 --> RNA["Thymus<br/>RNA-Seq<br/>Mus musculus"]
    A2 --> RNA
    A3 --> RNA
    A4 --> RNA
    A5 --> RNA
    A6 --> RNA

    style OSD244 fill:#534AB7,color:#fff
    style RNA fill:#1D9E75,color:#fff
```

---

👤 **User**
Find the assays that compare Space Flight vs. Ground Control at the 30 day and 60 day time points. Include all other factors for each assay such as sample collection conditions.

---

🧠 **Assistant**

There are **8 distinct assay nodes** matching Space Flight vs. Ground Control at 30-day and/or 60-day time points.

### ~30 day: Space Flight vs. Ground Control

**Assay `OSD-244-57da8b7ca3c3b4af08d72a00029a2c70`** — Group 1: **Space Flight**, Group 2: **Ground Control**
Secondary factors: `~30 day`, `Ground Control`, `On Earth`, `Upon euthanasia`, `Space Flight`

**Assay `OSD-244-d3af03333f10d1d48e9d3322d23f4638`** — Group 1: **Ground Control**, Group 2: **Space Flight** (inverse direction)
Secondary factors: `~30 day`, `On Earth`, `Space Flight`, `Upon euthanasia`, `Ground Control`

### ~60 day: Space Flight vs. Ground Control

**Assay `OSD-244-0a77ea7b391ab5c3c3546c1af0c3e2c8`** — Group 1: **Space Flight**, Group 2: **Ground Control**
Secondary factors: `~60 day`, `Carcass`, `Ground Control`, `On Earth`, `On ISS`, `Space Flight`

**Assay `OSD-244-471327308d673324961207f3de27d775`** — Group 1: **Ground Control**, Group 2: **Space Flight** (inverse)
Secondary factors: `~60 day`, `Carcass`, `On ISS`, `Space Flight`, `Ground Control`, `On Earth`

### Cross-time-point assays (differ in both flight condition and duration)

**Assay `OSD-244-fcfe5c9b…`** — SF ~30 day vs. GC ~60 day
**Assay `OSD-244-adb98a42…`** — SF ~60 day vs. GC ~30 day
**Assay `OSD-244-6f7245f7…`** — GC ~30 day vs. SF ~60 day
**Assay `OSD-244-86fc4d48…`** — GC ~60 day vs. SF ~30 day

### Summary table

| Assay ID (suffix) | Group 1 | Group 2 | Time factors |
|---|---|---|---|
| `0a77ea7b…` | Space Flight | Ground Control | ~60 day vs. ~60 day |
| `471327308d…` | Ground Control | Space Flight | ~60 day vs. ~60 day |
| `57da8b7c…` | Space Flight | Ground Control | ~30 day vs. ~30 day |
| `d3af0333…` | Ground Control | Space Flight | ~30 day vs. ~30 day |
| `fcfe5c9b…` | Space Flight | Ground Control | ~30 day vs. ~60 day |
| `adb98a42…` | Space Flight | Ground Control | ~60 day vs. ~30 day |
| `6f7245f7…` | Ground Control | Space Flight | ~30 day vs. ~60 day |
| `86fc4d48…` | Ground Control | Space Flight | ~60 day vs. ~30 day |

The 4 "pure" same-duration comparisons (`57da8b7c`, `0a77ea7b`, `d3af0333`, `471327308d`) are the clearest Space Flight vs. Ground Control contrasts at matched time points.

---

👤 **User**
Find the top 10 differentially up- and downregulated genes for Space Flight → Ground Control~30 day

---

🧠 **Assistant**

Results for assay **OSD-244-57da8b7ca3c3b4af08d72a00029a2c70** (Space Flight ~30 day → Ground Control ~30 day, thymus, *Mus musculus*).

### Top 10 upregulated in Space Flight (~30 day)

| Gene | log₂FC | adj p | SF mean | GC mean |
|---|---|---|---|---|
| *Sftpc* | +9.37 | 0.0063 | 6,662 | 11.0 |
| *Cldn18* | +6.77 | 0.0114 | 405 | 4.8 |
| *Sftpb* | +6.77 | 0.0104 | 1,815 | 17.6 |
| *Cxcl15* | +6.35 | 0.0163 | 623 | 8.7 |
| *Sfta2* | +6.17 | 0.097 | 35.9 | 1.3 |
| *Slc34a2* | +5.13 | 0.0071 | 2,087 | 60.6 |
| *Prss27* | +5.01 | 0.0050 | 39.1 | 29.6 |
| *Dbh* | +4.99 | 0.0096 | 31.8 | 278 |
| *Nkx2-5* | +4.65 | 0.063 | 24.8 | 1.8 |
| *Nppb* | +4.51 | 0.055 | 46.0 | 2.9 |

The top upregulated genes are enriched for **surfactant proteins** (*Sftpc*, *Sftpb*, *Sfta2*, *Slc34a2*) and a lung chemokine (*Cxcl15*) — suggesting possible lung tissue contamination in the thymus samples, or genuine spaceflight-induced ectopic expression.

### Top 10 downregulated in Space Flight (~30 day)

| Gene | log₂FC | adj p | SF mean | GC mean |
|---|---|---|---|---|
| *Cnfn* | −15.76 | 0.0080 | 145 | 170 |
| *Cldn34c6* | −6.64 | 0.0348 | 1.09 | 18.1 |
| *Gpr101* | −6.54 | 0.0086 | 1.09 | 17.1 |
| *Vmn2r42* | −6.32 | 0.057 | 1.07 | 14.2 |
| *Vmn2r74* | −6.30 | 0.093 | 1.09 | 14.5 |
| *Vmn1r28* | −6.27 | 0.0328 | 1.07 | 14.8 |
| *Vmn2r94* | −6.25 | 0.0409 | 1.30 | 19.0 |
| *A630073D07Rik* | −6.19 | 0.0168 | 1.47 | 28.4 |
| *Olfr1489* | −6.13 | 0.0279 | 1.17 | 19.3 |
| *Vmn2r66* | −6.01 | 0.0089 | 1.19 | 15.9 |

The downregulated set is dominated by **vomeronasal receptor genes** (*Vmn* family) and olfactory receptors (*Olfr1489*).

---

👤 **User**
Find the top 10 differentially up- and downregulated genes for Space Flight → Ground Control~60 day

---

🧠 **Assistant**

Results for assay **OSD-244-0a77ea7b391ab5c3c3546c1af0c3e2c8** (Space Flight ~60 day → Ground Control ~60 day, thymus, *Mus musculus*). All genes are highly significant — notably cleaner statistics than the 30-day comparison.

### Top 10 upregulated in Space Flight (~60 day)

| Gene | log₂FC | adj p | SF mean | GC mean | Notes |
|---|---|---|---|---|---|
| *Krt4* | +9.43 | 1.2×10⁻⁸ | 3,857 | 2.95 | Keratin, epithelial barrier |
| *Myh8* | +8.66 | 1.9×10⁻⁶ | 12,587 | 8.73 | Embryonic/perinatal myosin heavy chain |
| *Krt13* | +8.25 | 1.7×10⁻⁷ | 2,541 | 4.35 | Keratin, mucosal epithelium |
| *Klk11* | +6.74 | 0.0051 | 33.3 | 1.28 | Kallikrein serine protease |
| *Cfap97d2* | +6.59 | 2.6×10⁻⁴ | 23.0 | 1.05 | Cilia-associated protein |
| *Bpifa1* | +6.32 | 1.0×10⁻⁴ | 28,061 | 353 | Airway innate immunity |
| *Bpifb1* | +6.07 | 0.0030 | 897 | 14.3 | Airway secretory protein |
| *Gm36041* | +5.95 | 0.0018 | 48.8 | 1.75 | Predicted gene |
| *Scgb3a1* | +5.94 | 0.0012 | 1,806 | 30.5 | Secretoglobin, airway |
| *C730027H18Rik* | +5.84 | 0.0033 | 16.9 | 1.05 | Uncharacterized |

The upregulated set at 60 days shifts markedly toward **keratin/epithelial** (*Krt4*, *Krt13*), **muscle** (*Myh8*), and **airway secretory** genes (*Bpifa1*, *Bpifb1*, *Scgb3a1*) — a distinct signature from the surfactant-dominated 30-day picture.

### Top 10 downregulated in Space Flight (~60 day)

| Gene | log₂FC | adj p | SF mean | GC mean | Notes |
|---|---|---|---|---|---|
| *Ibsp* | −7.21 | 3.5×10⁻⁵ | 1.47 | 73.7 | Bone sialoprotein / mineralization |
| *Gm25682* | −6.12 | 0.0059 | 1.32 | 25.5 | Predicted gene |
| *Gm23686* | −5.31 | 0.0012 | 5.35 | 173 | Predicted gene |
| *Gm25189* | −4.98 | 0.034 | 2.92 | 61.4 | Predicted gene |
| *Gm23330* | −4.58 | 0.065 | 1.62 | 15.6 | Predicted gene |
| *LOC115490478* | −4.10 | 0.055 | 2.94 | 34.3 | Uncharacterized locus |
| *Gm8325* | −3.31 | 0.097 | 12.4 | 114 | Predicted gene |
| *Gm23511* | −3.28 | 0.043 | 4.07 | 30.7 | Predicted gene |
| *Dynlt2a3* | −3.27 | 0.032 | 1.39 | 5.31 | Dynein light chain |
| *Kcnh7* | −3.25 | 0.0055 | 2.13 | 12.3 | Voltage-gated K⁺ channel |

The most notable downregulated hit is **Ibsp** (bone sialoprotein) — consistent with known spaceflight-associated bone loss.

**Comparing 30-day vs. 60-day:** Surfactant/lung genes dominate at 30 days, while keratins and airway secretory genes lead at 60 days. *Ibsp* (bone) emerges as the clearest biologically interpretable downregulated hit at 60 days.

---

👤 **User**
Find the common differentially expressed genes for the ~30 day and ~60 duration time points

---

🧠 **Assistant**

There are **322 genes** significantly differentially expressed (adj p ≤ 0.05) at both ~30 and ~60 days in the Space Flight vs. Ground Control comparison. The scatter plot below shows the overall concordance — most genes fall along the diagonal, indicating the two time points agree closely in direction and magnitude.

```mermaid
quadrantChart
    title ~30 day vs ~60 day (Space Flight vs Ground Control)
    x-axis "log2FC ~30 day"
    y-axis "log2FC ~60 day"
    quadrant-1 Up both time points
    quadrant-2 Flip down-up
    quadrant-3 Down both time points
    quadrant-4 Flip up-down
    Sim2: [0.55, 0.85]
    Foxs1: [0.30, 0.56]
    Agt: [0.61, 0.70]
    Clec4f: [0.37, 0.55]
    F10: [0.56, 0.61]
    Alox15: [0.48, 0.61]
    Thbs1: [0.48, 0.37]
    Ifi27l2a: [0.45, 0.22]
    Fn1: [0.37, 0.43]
    Gm39079: [0.07, 0.59]
    Albfm1: [0.08, 0.55]
    Kcnh7: [0.20, 0.13]
    Hmgb1: [0.28, 0.28]
```

### Key biological clusters in the 322 shared genes

**Coagulation & liver-secreted proteins** (consistently ↑ in SF):
*F7*, *F10*, *F5*, *Ahsg*, *Saa3*, *C4b* — coagulation factors appearing ectopically in thymus.

**Lipid & eicosanoid metabolism** (consistently ↑):
*Alox15*, *Alox5*, *Alox5ap*, *Ltc4s*, *Ptges* — sustained inflammatory lipid signalling.

**Extracellular matrix remodelling** (consistently ↑):
*Fn1*, *Thbs1*, *Vim*, *Col6a1/3*, *Loxl2*, *Tgfbi*, *Mmp14*.

**Innate immune / myeloid infiltration** (consistently ↑):
*Itgam*, *Csf1r*, *Csf1*, *Cd14*, *Clec4d/4f*, *C5ar1*, *Lyz1*, *Napsa*.

**Direction-flipping genes** (~30d ↓ → ~60d ↑):
*Gm39079*, *Albfm1*, *Tmem45a2*, *Gm10319*, *Mgam*.

**Consistently downregulated:**
*Kcnh7*, *Itm2a*, *Nebl*, *Hmgb1*, *Lipa*.

### Top shared DEGs (dual time-point comparison)

| Gene | log₂FC 30d | log₂FC 60d | Direction |
|---|---|---|---|
| *Ly6g6c* | +4.34 | +4.58 | ↑ up both |
| *Agt* | +3.85 | +4.44 | ↑ up both |
| *Sim2* | +3.53 | +5.60 | ↑ up both (stronger at 60d) |
| *F10* | +3.50 | +3.81 | ↑ up both |
| *Alox15* | +3.00 | +3.83 | ↑ up both |
| *Foxs1* | +1.92 | +3.56 | ↑ up both (strengthens at 60d) |
| *Clec4f* | +2.30 | +3.47 | ↑ up both |
| *Gm39079* | −4.36 | +3.70 | ⇄ direction flip |
| *Albfm1* | −4.01 | +3.44 | ⇄ direction flip |
| *Kcnh7* | −2.55 | −3.25 | ↓ down both |
| *Nebl* | −1.72 | −1.23 | ↓ down both |

---

👤 **User**
`@spoke-genelab`: Map the mouse genes to the human orthologs

---

🧠 **Assistant**

Of the 322 common DEGs, **~145 unique mouse genes** have at least one annotated human ortholog via the `IS_ORTHOLOG_MGiG` predicate in `spoke-genelab`. The remaining genes are mouse-specific predicted genes (*Gm\** loci), ncRNA loci, and olfactory/vomeronasal receptors without clear human counterparts.

### One-to-many mappings

Several mouse genes map to gene families in humans due to lineage-specific expansions:

| Mouse gene | Human orthologs | Expansion type |
|---|---|---|
| *H2-D1* / *H2-K1* | **HLA-A, -B, -C, -E, -F, -G** | MHC class I family |
| *Saa3* | **SAA1, SAA2, SAA3P** | Serum amyloid A family |
| *Ifi27l2a* | **IFI27, IFI27L1, IFI27L2** | Interferon-induced family |
| *Apol9a/b* | **APOL1, APOL2, APOL3, APOL4** | Apolipoprotein L family |
| Mouse *Pira* | **LILRA1/2/4/5/6, LILRB3/5** | Leukocyte Ig-like receptors |

### Key human orthologs by pathway

| Mouse | Human | log₂FC 30d | log₂FC 60d | Pathway |
|---|---|---|---|---|
| *Agt* | **AGT** | +3.85 | +4.44 | Renin-angiotensin system |
| *F10* | **F10** | +3.50 | +3.81 | Coagulation cascade |
| *F7* | **F7** | +3.37 | +3.40 | Coagulation cascade |
| *F5* | **F5** | +2.86 | +3.01 | Coagulation cascade |
| *Alox15* | **ALOX15** | +3.00 | +3.83 | Eicosanoid / inflammation |
| *Alox5* | **ALOX5** | +2.08 | +1.55 | Eicosanoid / inflammation |
| *Fn1* | **FN1** | +2.31 | +2.66 | ECM remodelling |
| *Thbs1* | **THBS1** | +3.02 | +2.32 | ECM remodelling |
| *Itgam* | **ITGAM** | +1.83 | +2.28 | Myeloid / CD11b |
| *Csf1r* | **CSF1R** | +1.55 | +1.42 | Myeloid differentiation |
| *Spi1* | **SPI1** | +1.11 | +1.41 | Myeloid transcription factor |
| *Apoe* | **APOE** | +1.49 | +1.79 | Lipid transport |
| *Selp* | **SELP** | +1.95 | +2.33 | Vascular adhesion |
| *Hamp* | **HAMP** | +3.17 | +2.85 | Iron homeostasis / hepcidin |
| *H2-D1* | **HLA-A/B/C** | +1.17 | +1.07 | Antigen presentation |
| *Kcnh7* | **KCNH7** | −2.55 | −3.25 | Voltage-gated K⁺ channel |

---

👤 **User**
`@spoke-okn`: Which diseases are associated with these genes?

---

🧠 **Assistant**

Cross-referencing the 145 human ortholog genes against `spoke-okn` via the `ASSOCIATES_DaG` predicate yielded associations across **50+ unique diseases**. Below are the top disease groupings by number of associated genes.

### Disease associations by category

```mermaid
xychart-beta
    title "Number of spaceflight DEG orthologs per disease (top 20)"
    x-axis ["Liver dis.", "Hypertension", "Nervous sys.", "Diabetes", "Epilepsy", "CAD", "IBD", "Depressive", "Arterioscler.", "Schizophrenia", "Asthma", "COPD", "Dermatitis", "Leukemia", "Alzheimer's", "Gout", "Rheum. arth.", "Mult. scler.", "CKD", "Parkinson's"]
    y-axis "Gene count" 0 --> 25
    bar [24, 18, 16, 14, 14, 11, 10, 9, 8, 6, 8, 6, 9, 6, 3, 3, 5, 2, 3, 2]
```

### Key disease-gene connections

**Cardiovascular** (*AGT*, *SELP*, *FN1*, *LIPA*, *LDLR*, *TGFBR2*, *ELN*, *APOE*):
Coronary artery disease, arteriosclerosis, cerebrovascular disease, peripheral artery disease — coherent vascular remodelling signature.

**Immune/Inflammatory** (*SAA1/2*, *PADI4*, *MYRF*, *IL6R*, *NOD1/2*, *TLR5*, *ALOX5*, *PTGES*):
Rheumatoid arthritis, asthma, inflammatory bowel disease, multiple sclerosis.

**Neurological** (*SERPINA3*, *SPI1*, *APOE*, *C4A/B*, *FGFR1*, *PDGFRB*):
Alzheimer's disease, Parkinson's disease, epilepsy, schizophrenia.

**Cancer** — *TGFBR2* alone links to 15+ cancers (colorectal, breast, stomach, ovarian, thyroid, pancreatic, glioblastoma); *FN1* covers several solid tumours; *SPI1*/*ANPEP* link to leukemia.

**Notable single-gene highlights:**
- *APOL1* → African Trypanosomiasis + chronic kidney disease
- *PRG4* → Osteoarthritis
- *PADI4* → Rheumatoid arthritis (citrullination)
- *HAMP* → Iron deficiency anemia + thalassemia
- *SERPING1* → Urticaria (hereditary angioedema)

---

👤 **User**
Identify publications that mention these genes in the context of spaceflight or microgravity, and return: PMID, Title, Year, Brief relevance summary (1 sentence)

---

🧠 **Assistant**

Based on articles retrieved from PubMed, here are the most relevant publications linking the identified DEGs to spaceflight or microgravity contexts.

### Cardiovascular, ECM & Adhesion Molecules

| PMID | Title | Year | Relevance |
|---|---|---|---|
| [25197889](https://doi.org/10.3357/ASEM.3959.2014) | Plasma volume and flight duration effects on post-spaceflight soluble adhesion molecules | 2014 | Directly measures circulating **SELP** (sP-selectin) and sE-selectin in 22 astronauts pre/post-flight, showing SELP rises within 8 days of spaceflight. |
| [32344794](https://doi.org/10.3390/ijms21093031) | The Impact of Spaceflight and Simulated Microgravity on Cell Adhesion | 2020 | Comprehensive review demonstrating that **integrins, selectins (SELP), and fibronectin (FN1)** are dysregulated by microgravity across multiple immune and somatic cell types. |
| [17384275](https://doi.org/10.1196/annals.1378.034) | Microgravity signal ensnarls cell adhesion, cytoskeleton, and matrix proteins of rat osteoblasts | 2006 | Shuttle spaceflight experiment showing increased **FN1** and **VIM** mRNA in rat osteoblasts aboard the Space Shuttle under real microgravity. |
| [34760877](https://doi.org/10.3389/fbioe.2021.716184) | Platelets in Wound Healing: What Happens in Space? | 2021 | Reviews how microgravity reduces platelet **FN1** and vitronectin release, impairing coagulation and wound healing in astronauts. |
| [38158572](https://doi.org/10.3357/AMHP.6290.2024) | Venous Thromboembolism in Exploration Class Human Spaceflight | 2024 | Identifies upregulated coagulation markers and **SELP** as biomarkers of VTE risk in spaceflight, directly implicating the *F5/F7/F10* coagulation cluster. |
| [39702444](https://doi.org/10.1038/s41526-024-00450-z) | Sex-specific cardiovascular adaptations to simulated microgravity in Sprague-Dawley rats | 2024 | Demonstrates microgravity-induced aortic stiffening with altered collagen-to-**ELN (elastin)** ratios, directly relevant to *ELN/COL6* upregulation in OSD-244. |

### Hepcidin / Iron Metabolism

| PMID | Title | Year | Relevance |
|---|---|---|---|
| [28087888](https://doi.org/10.1113/EP086188) | Simulated microgravity decreases circulating iron in rats: role of inflammation-induced hepcidin upregulation | 2017 | Shows hindlimb suspension upregulates **HAMP** (hepcidin) mRNA in rat liver via IL-6/STAT3, directly explaining the *Hamp* upregulation observed in OSD-244 thymus. |
| [25565527](https://doi.org/10.3357/AMHP.4074.2015) | Excessive iron and weightlessness effects on the femurs and livers of rats | 2015 | Demonstrates simulated weightlessness amplifies iron deposition and serum ferritin increases, with **HAMP** as a mediator, in a rodent tail-suspension model. |

### Myeloid / Innate Immune Genes

| PMID | Title | Year | Relevance |
|---|---|---|---|
| [34074492](https://doi.org/10.1016/bs.ircmb.2021.01.004) | Implications of microgravity-induced cell signaling alterations upon cancer cell growth and host immunity | 2021 | Extensively reviews how microgravity alters **ITGAM/CD11b** and innate immune cell function (macrophages, dendritic cells) during spaceflight. |
| [36613598](https://doi.org/10.3390/ijms24010155) | Simulated Microgravity Influences Immunity-Related Biomarkers in Lung Cancer | 2023 | Under simulated microgravity, **NAPSA**, **LYZ**, and immune-related DEGs are upregulated in lung epithelial cells, mirroring the airway gene cluster in OSD-244. |

### TGF-β / ECM Remodelling

| PMID | Title | Year | Relevance |
|---|---|---|---|
| [30521385](https://doi.org/10.1096/fj.201802075R) | Microgravity-induced hepatogenic differentiation of rBMSCs on board the SJ-10 satellite | 2019 | Space-flown MSCs show reduced **VIM** and altered ECM gene expression with TGF-β pathway involvement during microgravity-induced hepatogenesis aboard an actual satellite. |
| [32539174](https://doi.org/10.1096/fj.202000216R) | Irisin prevents microgravity-induced impairment of osteoblast differentiation in vitro during the CRS-14 mission | 2020 | ISS experiment validating microgravity-induced downregulation of collagen I and ECM genes (**FN1**) in osteoblasts aboard the International Space Station. |

### ApoE / Cardiovascular Radiation Risk

| PMID | Title | Year | Relevance |
|---|---|---|---|
| [38054039](https://doi.org/10.3389/fphys.2023.1292033) | Lifetime evaluation of left ventricular structure and function in male ApoE null mice after gamma and space-type radiation | 2023 | Uses **APOE**-null mice to model space radiation-induced cardiovascular disease, showing simGCR radiation disrupts cardiac remodelling genes overlapping with the OSD-244 DEG set. |

### Hematopoietic Aging / Broad Immune DEGs

| PMID | Title | Year | Relevance |
|---|---|---|---|
| [40912236](https://doi.org/10.1016/j.stem.2025.07.013) | Nanobioreactor detection of space-associated hematopoietic stem and progenitor cell aging | 2025 | Multi-mission ISS study (SpX-24–27) showing spaceflight induces inflammatory cytokine dysregulation and clonal mutations in HSPCs — broader context for the myeloid gene cluster (*SPI1*, *CSF1R*, *ITGAM*) found in OSD-244. |

---

### Full analysis pipeline summary

```mermaid
flowchart TD
    A[spoke-genelab\nOSD-244 Rodent Research-6] --> B[20 assay nodes\nThymus RNA-Seq\nSF vs. GC / BC]
    B --> C1[30-day assay\n57da8b7c]
    B --> C2[60-day assay\n0a77ea7b]
    C1 --> D1["Top UP: Sftpc +9.4\nSurfactant cluster"]
    C1 --> D2["Top DOWN: Cnfn −15.8\nVomeronasal receptors"]
    C2 --> D3["Top UP: Krt4 +9.4\nKeratin/ECM shift"]
    C2 --> D4["Top DOWN: Ibsp −7.2\nBone sialoprotein"]
    C1 & C2 --> E[322 common DEGs\nadj p ≤ 0.05 both time points]
    E --> F[IS_ORTHOLOG_MGiG\n145 human orthologs]
    F --> G[spoke-okn\nASSOCIATES_DaG]
    G --> H["50+ diseases\nTop: liver dis. 24 genes\nhypertension 18 genes\nnervous sys. 16 genes"]
    E --> I[PubMed literature\n14 key publications]
    I --> J["PMID 28087888\nHAMP/hepcidin/microgravity\nPMID 25197889\nSELP in astronauts\nPMID 38054039\nAPOE cardiovascular/radiation"]

    style A fill:#534AB7,color:#fff
    style E fill:#1D9E75,color:#fff
    style G fill:#378ADD,color:#fff
    style H fill:#BA7517,color:#fff
    style I fill:#D85A30,color:#fff
```

---

*Created by [mcp-proto-okn](https://github.com/sbl-sdsc/mcp-proto-okn) 0.6.0 on 2026-03-17*

*Model: claude-sonnet-4-6*
