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132 changes: 90 additions & 42 deletions README.md
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![Alt text](_other/images/UNRAVEL_logo.png)

## UNRAVEL is a command line tool for:
* Voxel-wise analysis of fluorescent signals (e.g., c-Fos immunofluorescence) across the mouse brains in atlas space
* Validation of hot/cold spots via cell/label density quantification at cellular resolution

## Publications:
* UNRAVELing the synergistic effects of psilocybin and environment on brain-wide immediate early gene expression in mice
* [Neuropsychopharmacology](https://www.nature.com/articles/s41386-023-01613-4)

## IF/iDISCO+/LSFM guide:
[Heifets lab guide to immunofluorescence staining, iDISCO+, & lightsheet fluorescence microscopy](https://docs.google.com/document/d/16yowBhiBQWz8_VX2t9Rf6Xo3Ub4YPYD6qeJP6vJo6P4/edit?usp=sharing)

## UNRAVEL guide:
* Example workflow for region-wise and voxel-wise c-Fos+ cell densities:
* prep_reg.py (To see help, run: prep_reg.py -h)
* copy_tifs.py
* brain_mask.py
* reg.py
* check_reg.py
* regional_cell_densities.py
* regional_cell_densities_summary.py
* prep_vstats.py
* z-score.py
* aggregate_files_from_sample_dirs.py
* whole_to_LR_avg.py
* vstats.py
* fdr_range.py
* fdr.py
* recursively_mirror_rev_cluster_indices.py
* ilastik_pixel_classification.py
* validate_clusters.py
* valid_clusters_summary.py

\
Please send questions/suggestions to:
* Daniel Ryskamp Rijsketic ([email protected])
* Austen Casey ([email protected])
* Boris Heifets ([email protected])

\
For command line interface help, please review [Unix tutorials](https://andysbrainbook.readthedocs.io/en/latest/index.html)
[![UNRAVEL Logo](https://b-heifets.github.io/UNRAVEL/_static/UNRAVEL_logo.png)](https://b-heifets.github.io/UNRAVEL/)


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<a href="https://www.nature.com/articles/s41386-023-01613-4" target="_blank">
<video width="100%" autoplay muted playsinline>
<source src="https://b-heifets.github.io/UNRAVEL/_static/psilocybin_up_valid_clusters.mp4" type="video/mp4">
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<a href="https://www.nature.com/articles/s41386-023-01613-4" target="_blank">
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<source src="https://b-heifets.github.io/UNRAVEL/_static/psilocybin_up_sunburst.mp4" type="video/mp4">
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</a>
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</div>

### UN-biased high-Resolution Analysis and Validation of Ensembles using Light sheet images
* UNRAVEL is a [Python](https://www.python.org/) package & command line tool for the analysis of brain-wide imaging data, automating:
* Registration of brain-wide images to a common atlas space
* Quantification of cell/label densities across the brain
* Voxel-wise analysis of fluorescent signals and cluster correction
* Validation of hot/cold spots via cell/label density quantification at cellular resolution
* [UNRAVEL GitHub repository](https://github.com/b-heifets/UNRAVEL/tree/dev)
* [Initial UNRAVEL publication](https://www.nature.com/articles/s41386-023-01613-4)
* UNRAVEL was developed by [the Heifets lab](https://heifetslab.stanford.edu/) and [TensorAnalytics](https://sites.google.com/view/tensoranalytics/home?authuser=0)
* Additional support was provided by [the Shamloo lab](https://med.stanford.edu/neurosurgery/research/shamloo.html)


![Heifets Lab](https://b-heifets.github.io/UNRAVEL/_static/Heifets_lab_logo.png)

---

### *Please see [UNRAVEL documentation](https://b-heifets.github.io/UNRAVEL/) for guides on [installation](https://b-heifets.github.io/UNRAVEL/installation.html) and [anaysis](https://b-heifets.github.io/UNRAVEL/guide.html)*

---

### UNRAVEL visualizer
* [UNRAVEL visualizer](https://heifetslab-unravel.org/) is a web-based tool for visualizing and exploring 3D maps output from UNRAVEL
* [UNRAVEL visualizer GitHub repo](https://github.com/MetaCell/cfos-visualizer/)
* Developed by [MetaCell](https://metacell.us/) with support from the [Heifets lab](https://heifetslab.stanford.edu/)

![UNRAVEL visualizer](https://b-heifets.github.io/UNRAVEL/_static/UNRAVEL_visualizer.png)

### Contact us
If you have any questions, suggestions, or are interested in collaborations and contributions, please reach out to us.

### Developers
* **Daniel Ryskamp Rijsketic** (lead developer and maintainer) - [[email protected]](mailto:[email protected])
* **Austen Casey** (developer) - [[email protected]](mailto:[email protected])
* **MetaCell** (UNRAVEL visualizer developers) - [[email protected]](mailto:[email protected])
* **Boris Heifets** (PI) - [[email protected]](mailto:[email protected])

### Additional contributions from
* **Mehrdad Shamloo** (PI) - [[email protected]](mailto:[email protected])
* **Daniel Barbosa** (early contributer and guidance) - [[email protected]](mailto:[email protected])
* **Wesley Zhao** (guidance) - [[email protected]](mailto:[email protected])
* **Nick Gregory** (guidance) - [[email protected]](mailto:[email protected])

### Main dependencies
* [Allen Institute for Brain Science](https://portal.brain-map.org/)
* [FSL](https://fsl.fmrib.ox.ac.uk/fsl/fslwiki)
* [fslpy](https://git.fmrib.ox.ac.uk/fsl/fslpy)
* [ANTsPy](https://github.com/ANTsX/ANTsPy)
* [Ilastik](https://www.ilastik.org/)
* [nibabel](https://nipy.org/nibabel/)
* [numpy](https://numpy.org/)
* [scipy](https://www.scipy.org/)
* [pandas](https://pandas.pydata.org/)
* [cc3d](https://pypi.org/project/connected-components-3d/)
* Registration and warping workflows were inspired by [MIRACL](https://miracl.readthedocs.io/en/latest/)
* We adapted [LSFM/iDISCO+ atlases](https://pubmed.ncbi.nlm.nih.gov/33063286/) from [Gubra](https://www.gubra.dk/cro-services/3d-imaging/)

### Support is welcome for
* Analysis of new datasets
* Development of new features
* Maintenance of the codebase
* Guidance of new users
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14 changes: 7 additions & 7 deletions unravel/docs/_build/html/_sources/index.rst.txt
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Expand Up @@ -107,16 +107,16 @@ Developers
* **Boris Heifets** (PI) - `[email protected] <mailto:[email protected]>`_


Additional contributions from:
------------------------------
Additional contributions from
-----------------------------
* **Mehrdad Shamloo** (PI) - `[email protected] <mailto:[email protected]>`_
* **Daniel Barbosa** (early contributer and guidance) - `[email protected] <mailto:[email protected]>`_
* **Wesley Zhao** (guidance) - `[email protected] <mailto:[email protected]>`_
* **Nick Gregory** (guidance) - `[email protected] <mailto:[email protected]>`_


Main dependencies:
------------------------------------------------
Main dependencies
-----------------
* `Allen Institute for Brain Science <https://portal.brain-map.org/>`_
* `FSL <https://fsl.fmrib.ox.ac.uk/fsl/fslwiki>`_
* `fslpy <https://git.fmrib.ox.ac.uk/fsl/fslpy>`_
Expand All @@ -128,10 +128,10 @@ Main dependencies:
* `pandas <https://pandas.pydata.org/>`_
* `cc3d <https://pypi.org/project/connected-components-3d/>`_
* Registration and warping workflows were inspired by `MIRACL <https://miracl.readthedocs.io/en/latest/>`_
* We adapted `LSFM/iDISCO+ atlases <https://pubmed.ncbi.nlm.nih.gov/33063286/>`_ from `Gubra <https://www.gubra.dk/cro-services/3d-imaging/>`_


Support is welcome for:
-----------------------
Support is welcome for
----------------------
* Analysis of new datasets
* Development of new features
* Maintenance of the codebase
Expand Down
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Expand Up @@ -86,7 +86,7 @@ Add support for conda
```

8. **Download atlas/template files and locate them in `./atlas/`:**
[Google Drive Link](https://drive.google.com/drive/folders/1WE0mCJNT6IcqccMxuxUyog5-mYXM8q06?usp=share_link)
[Google Drive Link](https://drive.google.com/drive/folders/1iZjQlPc2kPagnVsjWEFFObLlkSc2yRf9?usp=sharing)

9. **Install Ilastik:**
- Download the Ilastik installer from the [Ilastik website](https://www.ilastik.org/download.html).
Expand Down
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Expand Up @@ -410,7 +410,7 @@ <h2>Developers<a class="headerlink" href="#developers" title="Link to this headi
</ul>
</section>
<section id="additional-contributions-from">
<h2>Additional contributions from:<a class="headerlink" href="#additional-contributions-from" title="Link to this heading">#</a></h2>
<h2>Additional contributions from<a class="headerlink" href="#additional-contributions-from" title="Link to this heading">#</a></h2>
<ul class="simple">
<li><p><strong>Mehrdad Shamloo</strong> (PI) - <a class="reference external" href="mailto:shamloo&#37;&#52;&#48;stanford&#46;edu">shamloo<span>&#64;</span>stanford<span>&#46;</span>edu</a></p></li>
<li><p><strong>Daniel Barbosa</strong> (early contributer and guidance) - <a class="reference external" href="mailto:Dbarbosa&#37;&#52;&#48;pennmedicine&#46;upenn&#46;edu">Dbarbosa<span>&#64;</span>pennmedicine<span>&#46;</span>upenn<span>&#46;</span>edu</a></p></li>
Expand All @@ -419,7 +419,7 @@ <h2>Additional contributions from:<a class="headerlink" href="#additional-contri
</ul>
</section>
<section id="main-dependencies">
<h2>Main dependencies:<a class="headerlink" href="#main-dependencies" title="Link to this heading">#</a></h2>
<h2>Main dependencies<a class="headerlink" href="#main-dependencies" title="Link to this heading">#</a></h2>
<ul class="simple">
<li><p><a class="reference external" href="https://portal.brain-map.org/">Allen Institute for Brain Science</a></p></li>
<li><p><a class="reference external" href="https://fsl.fmrib.ox.ac.uk/fsl/fslwiki">FSL</a></p></li>
Expand All @@ -432,10 +432,11 @@ <h2>Main dependencies:<a class="headerlink" href="#main-dependencies" title="Lin
<li><p><a class="reference external" href="https://pandas.pydata.org/">pandas</a></p></li>
<li><p><a class="reference external" href="https://pypi.org/project/connected-components-3d/">cc3d</a></p></li>
<li><p>Registration and warping workflows were inspired by <a class="reference external" href="https://miracl.readthedocs.io/en/latest/">MIRACL</a></p></li>
<li><p>We adapted <a class="reference external" href="https://pubmed.ncbi.nlm.nih.gov/33063286/">LSFM/iDISCO+ atlases</a> from <a class="reference external" href="https://www.gubra.dk/cro-services/3d-imaging/">Gubra</a></p></li>
</ul>
</section>
<section id="support-is-welcome-for">
<h2>Support is welcome for:<a class="headerlink" href="#support-is-welcome-for" title="Link to this heading">#</a></h2>
<h2>Support is welcome for<a class="headerlink" href="#support-is-welcome-for" title="Link to this heading">#</a></h2>
<ul class="simple">
<li><p>Analysis of new datasets</p></li>
<li><p>Development of new features</p></li>
Expand Down Expand Up @@ -693,9 +694,9 @@ <h1>Indices<a class="headerlink" href="#indices" title="Link to this heading">#<
<li class="toc-h2 nav-item toc-entry"><a class="reference internal nav-link" href="#unravel-visualizer">UNRAVEL visualizer</a></li>
<li class="toc-h2 nav-item toc-entry"><a class="reference internal nav-link" href="#contact-us">Contact us</a></li>
<li class="toc-h2 nav-item toc-entry"><a class="reference internal nav-link" href="#developers">Developers</a></li>
<li class="toc-h2 nav-item toc-entry"><a class="reference internal nav-link" href="#additional-contributions-from">Additional contributions from:</a></li>
<li class="toc-h2 nav-item toc-entry"><a class="reference internal nav-link" href="#main-dependencies">Main dependencies:</a></li>
<li class="toc-h2 nav-item toc-entry"><a class="reference internal nav-link" href="#support-is-welcome-for">Support is welcome for:</a></li>
<li class="toc-h2 nav-item toc-entry"><a class="reference internal nav-link" href="#additional-contributions-from">Additional contributions from</a></li>
<li class="toc-h2 nav-item toc-entry"><a class="reference internal nav-link" href="#main-dependencies">Main dependencies</a></li>
<li class="toc-h2 nav-item toc-entry"><a class="reference internal nav-link" href="#support-is-welcome-for">Support is welcome for</a></li>
</ul>
</li>
<li class="toc-h1 nav-item toc-entry"><a class="reference internal nav-link" href="#indices">Indices</a></li>
Expand Down
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Expand Up @@ -444,7 +444,7 @@ <h2>Installing UNRAVEL on Linux or WSL<a class="headerlink" href="#installing-un
</div>
<ol class="arabic" start="8">
<li><p><strong>Download atlas/template files and locate them in <code class="docutils literal notranslate"><span class="pre">./atlas/</span></code>:</strong>
<a class="reference external" href="https://drive.google.com/drive/folders/1WE0mCJNT6IcqccMxuxUyog5-mYXM8q06?usp=share_link">Google Drive Link</a></p></li>
<a class="reference external" href="https://drive.google.com/drive/folders/1iZjQlPc2kPagnVsjWEFFObLlkSc2yRf9?usp=sharing">Google Drive Link</a></p></li>
<li><p><strong>Install Ilastik:</strong></p>
<ul>
<li><p>Download the Ilastik installer from the <a class="reference external" href="https://www.ilastik.org/download.html">Ilastik website</a>.</p></li>
Expand Down
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14 changes: 7 additions & 7 deletions unravel/docs/index.rst
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Expand Up @@ -107,16 +107,16 @@ Developers
* **Boris Heifets** (PI) - `[email protected] <mailto:[email protected]>`_


Additional contributions from:
------------------------------
Additional contributions from
-----------------------------
* **Mehrdad Shamloo** (PI) - `[email protected] <mailto:[email protected]>`_
* **Daniel Barbosa** (early contributer and guidance) - `[email protected] <mailto:[email protected]>`_
* **Wesley Zhao** (guidance) - `[email protected] <mailto:[email protected]>`_
* **Nick Gregory** (guidance) - `[email protected] <mailto:[email protected]>`_


Main dependencies:
------------------------------------------------
Main dependencies
-----------------
* `Allen Institute for Brain Science <https://portal.brain-map.org/>`_
* `FSL <https://fsl.fmrib.ox.ac.uk/fsl/fslwiki>`_
* `fslpy <https://git.fmrib.ox.ac.uk/fsl/fslpy>`_
Expand All @@ -128,10 +128,10 @@ Main dependencies:
* `pandas <https://pandas.pydata.org/>`_
* `cc3d <https://pypi.org/project/connected-components-3d/>`_
* Registration and warping workflows were inspired by `MIRACL <https://miracl.readthedocs.io/en/latest/>`_
* We adapted `LSFM/iDISCO+ atlases <https://pubmed.ncbi.nlm.nih.gov/33063286/>`_ from `Gubra <https://www.gubra.dk/cro-services/3d-imaging/>`_


Support is welcome for:
-----------------------
Support is welcome for
----------------------
* Analysis of new datasets
* Development of new features
* Maintenance of the codebase
Expand Down
2 changes: 1 addition & 1 deletion unravel/docs/installation.md
Original file line number Diff line number Diff line change
Expand Up @@ -86,7 +86,7 @@ Add support for conda
```

8. **Download atlas/template files and locate them in `./atlas/`:**
[Google Drive Link](https://drive.google.com/drive/folders/1WE0mCJNT6IcqccMxuxUyog5-mYXM8q06?usp=share_link)
[Google Drive Link](https://drive.google.com/drive/folders/1iZjQlPc2kPagnVsjWEFFObLlkSc2yRf9?usp=sharing)

9. **Install Ilastik:**
- Download the Ilastik installer from the [Ilastik website](https://www.ilastik.org/download.html).
Expand Down

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