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2 changes: 1 addition & 1 deletion Gemfile
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Expand Up @@ -7,4 +7,4 @@ group :jekyll_plugins do
gem "github-pages", "~> 207"
gem "jekyll-seo-tag", "~> 2.6.1"
gem "jekyll-redirect-from"
end
end
2 changes: 1 addition & 1 deletion README.md
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Expand Up @@ -100,7 +100,7 @@ Below is information about the front matter options for each of the site's colle
- **view_data_link** - Link to an associated data page (displays a 'View Data' button)
- **info_link** - Link to the associated (off-site) info page
- **show_page_link** (boolean) - If *true*, will display a link to this entry's standalone summary page whereever a list of dataset entries is shown (eg homepage, Data landing page). Content within the body of the entry will be displayed on this summary page.
- **tags** (array) - List of tags that can be used to filter on when using the *cards.html* include file.
- **tags** (array) - List of tags that can be used to filter on when using the *cards.html* include file. For stories: auto, curated, narrated


### funding ###
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23 changes: 5 additions & 18 deletions _atlas-datasets/cichowski-santagata-sorger-2024.md
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Expand Up @@ -9,8 +9,8 @@ data:
journal: 'TBA'
authors: 'Schade A, Perurena N, Yang Y, Rodriguez CL, Krishnan A, Loi P, Mastellone GM, Pilla NF, Watanabe M, Xu Y, Nguyen V, Ota K, Davis RA, Mattioli K, Xiang D, Zoeller JL, Morganti S, Garrido-Castro AC, Tolaney S, Li Z, Barbie DA, Sorger PK, Helin K, Santagata S, Knott SRV, Cichowski K.'
description: 'Triple negative breast cancer (TNBC) is the most aggressive breast cancer subtype and has the highest rate of recurrence. The predominant standard of care for advanced TNBC is systemic chemotherapy with or without immunotherapy, however responses are typically short-lived. Thus, there is an urgent need to develop more effective treatments. PI3K pathway components represent plausible therapeutic targets, as at least 70% of TNBCs have PIK3CA/AKT1/PTEN alterations. However, unlike hormone receptor-positive tumors, it is still unclear if or how PI3K pathway inhibitors will be effective in triple-negative disease. Here we describe a promising AKT inhibitor-based therapeutic combination for TNBC. Specifically, we show that AKT inhibitors potently synergize with agents that suppress the histone methyltransferase, EZH2, and promote robust tumor regression in multiple TNBC models in vivo. AKT and EZH2 inhibitors exert these effects by first cooperatively driving basal-like TNBC cells into a more differentiated, luminal-like state, which cannot be effectively induced by either agent alone. Once differentiated, these agents kill TNBCs by hijacking signals that normally drive mammary gland involution. Importantly, using a machine learning approach we developed a classifier that can be used to predict sensitivity. Together these findings identify a promising therapeutic strategy for this highly aggressive tumor type and illustrate how deregulated epigenetic enzymes can insulate tumors from oncogenic vulnerabilities. These studies also reveal how developmental tissue-specific cell death pathways may be co-opted for therapeutic benefit.'
links:
- Data Access: https://github.com/labsyspharm/cichowski-santagata-sorger-2024/
links:
- Primary data Access: https://github.com/labsyspharm/cichowski-santagata-sorger-2024/
---

{% assign urlParts = page.url | split: '/' %}
Expand All @@ -20,33 +20,20 @@ links:
sectionId=sectionId
pubData=page.data
thumbnailDir=sectionId %}

## Contents
* [Graphical Abstract](#graphical-abstract)
* [Data Access](#data-access)
* [Funding](#funding)
<br>

### Graphical Abstract
{% include enlarge-image.html src='publications/cichowski-santagata-sorger-2024.PNG' alt='EZH2 + AKT inhibitors in TNBC' %}

### Data Explorations
<br>

{%
assign stories = site.data-cards
| where_exp: "item", "item.url contains 'cichowski-santagata-sorger-2024'"
| where_exp: "item", "item.hide != true"
%}

{% assign dataCardArray = '' | split: '' %}
{% for s in stories %}
{% unless s.url contains '-overview' %}
{% assign dataCardArray = dataCardArray | push: s %}
{% endunless %}
{% endfor %}

{% if dataCardArray.size > 0 %}
{% include cards.html cards=dataCardArray %}
{% endif %}
{% include minerva-story-sorting-pubs.md %}

## Data Access
Instructions to access data will be posted to the [GitHub repository](https://github.com/labsyspharm/cichowski-santagata-sorger-2024/) associated with this publication.
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17 changes: 10 additions & 7 deletions _atlas-datasets/du-lin-rashid-nat-protoc-2019.md
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Expand Up @@ -9,8 +9,9 @@ redirect_from:
data:
publication:
title: Qualifying antibodies for image-based immune profiling and multiplexed tissue imaging
authors: Du Z, Lin JR, Rashid R, Maliga Z, Wang S, Aster J, Izar B, Sorger PK, Santagata S.
authors: Du Z, Lin JR, Rashid R, Maliga Z, Wang S, Aster J, Izar B, Sorger PK, Santagata S
journal: "Nat Protoc. 2019 Oct; 14(10): 2900-2930. PMID: 31534232."
description: Multiplexed tissue imaging enables precise, spatially resolved enumeration and characterization of cell types and states in human resection specimens. A growing number of methods applicable to formalin-fixed, paraffin-embedded (FFPE) tissue sections have been described, the majority of which rely on antibodies for antigen detection and mapping. This protocol provides step-by-step procedures for confirming the selectivity and specificity of antibodies used in fluorescence-based tissue imaging and for the construction and validation of antibody panels. Although the protocol is implemented using tissue-based cyclic immunofluorescence (t-CyCIF) as an imaging platform, these antibody-testing methods are broadly applicable. We demonstrate assembly of a 16-antibody panel for enumerating and localizing T cells and B cells, macrophages, and cells expressing immune checkpoint regulators. The protocol is accessible to individuals with experience in microscopy and immunofluorescence; some experience in computation is required for data analysis. A typical 30-antibody dataset for 20 FFPE slides can be generated within 2 weeks.
links:
- Raw Data: https://www.synapse.org/#!Synapse:syn17865732/wiki/592782
- Publication: https://www.nature.com/articles/s41596-019-0206-y
Expand Down Expand Up @@ -51,10 +52,12 @@ data:
pubData=page.data
thumbnailDir=sectionId %}

## Available images
{:.mt-5}
<br>

{% include atlas-dataset-cards.html
sectionId=sectionId
pubData=page.data
thumbnailDir=sectionId %}
{%
assign stories = site.data-cards
| where_exp: "item", "item.url contains 'du-lin-rashid-nat-protoc-2019'"
| where_exp: "item", "item.hide != true"
%}

{% include minerva-story-sorting-pubs.md %}
32 changes: 6 additions & 26 deletions _atlas-datasets/gaglia-2022.md
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Expand Up @@ -12,6 +12,8 @@ data:
links:
- Publication: https://doi.org/10.1038/s41556-022-00860-9
- PubMed: https://pubmed.ncbi.nlm.nih.gov/35292783/
- Access Primary Data: /atlas-datasets/gaglia-2022#primary-data-access

---
{% assign urlParts = page.url | split: '/' %}
{% assign sectionId = urlParts[-1] %}
Expand All @@ -21,44 +23,22 @@ data:
pubData=page.data
thumbnailDir=sectionId %}


## Contents
* [__Data Explorations__: MINERVA Stories summarizing key findings and
data](#data-explorations)
* [__Data Overviews__: MINERVA Stories showing individual H&E and CyCIF
images](#data-overviews)
* [__Primary Data Access__: List of available data files](#primary-data-access)


## Data Explorations
**Data Explorations are like museum guides and exploit the digital docents in MINERVA to guide readers through the complexities of a large image dataset via a series of narrated stories and waypoints.**
<br>

{%
assign stories = site.data-cards
| where_exp: "item", "item.url contains 'gaglia-2022/'"
| where_exp: "item", "item.url contains 'gaglia-2022'"
| where_exp: "item", "item.hide != true"
%}

{% assign dataCardArray = '' | split: '' %}
{% for s in stories %}
{% unless s.url contains '-overview' %}
{% assign dataCardArray = dataCardArray | push: s %}
{% endunless %}
{% endfor %}
{% include minerva-story-sorting-pubs.md %}

{% if dataCardArray.size > 0 %}
{% include cards.html cards=dataCardArray %}
{% endif %}

## Data Overviews

The multiplexed T-CyCIF images can be viewed on [Omero](https://omero.hms.harvard.edu/webclient/?show=project-8863)

## Analysis

Image analysis matlab codes can be found at [www.github.com/santagatalab/manuscripts-codes-gaglia-kabraji-2021](www.github.com/santagatalab/manuscripts-codes-gaglia-kabraji-2021)

## Primary Data Access
You can vew the multiplexed t-CyCIF images on [Omero](https://omero.hms.harvard.edu/webclient/?show=project-8863).

<details>
<summary>Download the primary data</summary>
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39 changes: 6 additions & 33 deletions _atlas-datasets/gray-rosenbluth-selfors-2022.md
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Expand Up @@ -13,6 +13,7 @@ data:
- Publication: https://doi.org/10.1016/j.devcel.2022.05.003
- Sequencing: https://singlecell.broadinstitute.org/single_cell/study/SCP1731/a-human-breast-atlas-integrating-single-cell-proteomics-and-transcriptomics
- CyTOF: https://data.mendeley.com/datasets/pcftzv8w63/1
- Gray BRCA Atlas: https://www.graybrcaatlas.org/
---

{% assign urlParts = page.url | split: '/' %}
Expand All @@ -23,12 +24,7 @@ data:
pubData=page.data
thumbnailDir=sectionId %}


## Contents
* [Key Findings](#key-findings)
* [Data Stories](#data-stories)
* [Explore Tissue Images](#explore-tissue-images)

<br>

### Key Findings
- Multimodal single-cell analyses identify breast epithelial and stromal subtypes
Expand All @@ -39,39 +35,16 @@ data:

- Subtypes of the three major epithelial lineages are maintained in organoid cultures

{% include enlarge-image.html src='publications/a-human-breast-atlas-integrating-single-cell-proteomics-and-transcriptomics.jpg' float='center' alt='Highlighted epithelial cell subtypes: 1. Young nulliparous (AP2: Proliferative alveolar progenitors), 2. Aging associated (BL: Basal-luminal alveolar cells and BA1: Contractile ductal myoepithelial cells), 3. BRCA2 mutation associated (HS1 - ER-active hormone-sensing luminal cells), and 4. Parity associated (AP1: Parity-associated alveolar progenitors)' %}

### Data Stories
Data Stories are data visualizations that guide readers through the complexities of a large dataset through filters, search, or narrated image waypoints.

{%
assign overviews = site.data-cards
| where_exp: "item", "item.url contains 'gray-rosenbluth-selfors-2022/'"
| where_exp: "item", "item.hide != true"
| where_exp: "item", "item.tags contains 'Overview'"
%}

{% if overviews.size > 0 %}
{% include cards.html cards=overviews %}
{% endif %}
{% include enlarge-image.html src='/images/publications/a-breast-atlas-integrating-single-cell-proteomics-and-transcriptomics.jpg' float='center' alt='Highlighted epithelial cell subtypes: 1. Young nulliparous (AP2: Proliferative alveolar progenitors), 2. Aging associated (BL: Basal-luminal alveolar cells and BA1: Contractile ductal myoepithelial cells), 3. BRCA2 mutation associated (HS1 - ER-active hormone-sensing luminal cells), and 4. Parity associated (AP1: Parity-associated alveolar progenitors)' %}

### Explore Tissue Images
Access the minimally processed, unannotated Level 2 images associated with this publication. Click any of the following thumbnail images for an interactive view of the full-resolution images.
<br>

{%
assign stories = site.data-cards
| where_exp: "item", "item.url contains 'gray-rosenbluth-selfors-2022/'"
| where_exp: "item", "item.hide != true"
| where_exp: "item", "item.tags contains 'CyCIF'"
%}

{% assign dataCardArray = '' | split: '' %}
{% for s in stories %}
{% unless s.url contains '-overview' %}
{% assign dataCardArray = dataCardArray | push: s %}
{% endunless %}
{% endfor %}
{% include minerva-story-sorting-pubs.md %}


{% if dataCardArray.size > 0 %}
{% include cards.html cards=dataCardArray %}
{% endif %}
27 changes: 8 additions & 19 deletions _atlas-datasets/guerriero-lin-santagata-2023.md
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Expand Up @@ -9,8 +9,9 @@ data:
journal: 'npj Breast Cancer (2024). DOI: [10.1038/s41523-023-00605-3](https://doi.org/10.1038/s41523-023-00605-3)'
authors: 'Guerriero JL, Lin JR, Pastorello RG, Du Z, Chen YA, Townsend M, Shimada K, Hughes ME, Ren S, Tayob N, Zheng K, Mei S, Patterson A, Taneja K, Metzger O, Tolaney SM, Lin NU, Dillon DA, Schnitt SJ, Sorger PK, Mittendorf EA, Santagata S'
description: 'Emerging data suggests that HER2 intratumoral heterogeneity (ITH) is associated with therapy resistance, highlighting the need for new strategies to assess HER2 ITH. A promising approach is leveraging multiplexed tissue analysis techniques such as cyclic immunofluorescence (CyCIF), which enable visualization and quantification of 10-60 antigens at single-cell resolution from individual tissue sections. In this study, we qualified a breast cancer specific antibody panel, including HER2, ER and PR, for multiplexed tissue imaging. We then compared the performance of these antibodies against established clinical standards using pixel-, cell- and tissue-level analyses, utilizing 866 tissue cores (representing 294 patients). To ensure reliability, the CyCIF antibodies were qualified against HER2 immunohistochemistry (IHC) and fluorescence in situ hybridization (FISH) data from the same samples. Our findings demonstrate the successful qualification of a breast cancer antibody panel for CyCIF, showing high concordance with established clinical antibodies. Subsequently, we employed the qualified antibodies, along with antibodies for CD45, CD68, PD-L1, p53, Ki67, pRB and AR to characterize 567 HER2+ invasive breast cancer samples from 189 patients. Through single-cell analysis we identified four distinct cell clusters within HER2+ breast cancer exhibiting heterogeneous HER2 expression. Furthermore, these clusters displayed variations in ER, PR, p53, AR and PD-L1 expression. To quantify the extent of heterogeneity, we calculated heterogeneity scores based on the diversity among these clusters. Our analysis revealed expression patterns that are relevant to breast cancer biology, with correlations to HER2 ITH and potential relevance to clinical outcome.'
links:
- Publication: https://doi.org/10.1038/s41523-023-00605-3
links:
- Publication: https://doi.org/10.1038/s41523-023-00605-3
- Access Primary Data: /atlas-datasets/guerriero-lin-santagata-2023#data-access
---

{% assign urlParts = page.url | split: '/' %}
Expand All @@ -21,32 +22,20 @@ links:
pubData=page.data
thumbnailDir=sectionId %}

## Contents
* [Graphical Abstract](#graphical-abstract)
* [Data Access](#data-access)
* [Funding](#funding)
<br>

### Graphical Abstract
{% include enlarge-image.html src='publications/guerriero-lin-santagata-2023-compressed.png' alt='Figure 1. Overview of fluorescent CyCIF antibody qualification against antibodies used in the clinical laboratory' %}
{% include enlarge-image.html src='publications/guerriero-lin-santagata-2023-crop.png' alt='Figure 1. Overview of fluorescent CyCIF antibody qualification against antibodies used in the clinical laboratory' %}

### Data Explorations
<br>

{%
assign stories = site.data-cards
| where_exp: "item", "item.url contains 'guerriero-lin-santagata-2023/'"
| where_exp: "item", "item.hide != true"
| where_exp: "item", "item.hide != false"
%}

{% assign dataCardArray = '' | split: '' %}
{% for s in stories %}
{% unless s.url contains '-overview' %}
{% assign dataCardArray = dataCardArray | push: s %}
{% endunless %}
{% endfor %}

{% if dataCardArray.size > 0 %}
{% include cards.html cards=dataCardArray %}
{% endif %}
{% include minerva-story-sorting-pubs.md %}

## Data Access
Instructions to access data will be posted to the [GitHub repository](https://github.com/labsyspharm/npjbcancer2023) associated with this publication.
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8 changes: 5 additions & 3 deletions _atlas-datasets/keenan-2020.md
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Expand Up @@ -5,7 +5,7 @@ section_id: data

data:
publication:
title: Clinical efficacy and molecular response correlates of the Wee1 inhibitor adavosertib with cisplatin in metastatic triple-negative breast cancer (mTNBC)
title: Clinical efficacy and molecular response correlates of the Wee1 inhibitor adavosertib with cisplatin in metastatic triple-negative breast cancer
authors: Keenan T., Li T., Vallius T., Guerriero J.L., Tayob N., Kochupurakkal B., Davis J., Pastorello R., Tahara R.K., Anderson L., Conway J., He M.X., Shannon E., Godin R.E., Sorger P.K., D’Andrea A., Overmoyer B., Winer E.P., Mittendorf E.A., Van Allen E., Shapiro G.I., Tolaney S.M.
journal: "Clinical Cancer Research, 2(1), 66-82. PMID: 33257427"
description: Selective inhibition of the negative cell cycle regulator WEE1 may enhance the efficacy of DNA-damaging agents by reducing DNA damage repair. These are multiplexed cyclic immunofluorescence on paired pre- and post-WEE1 inhibitor tumor biopsies, from the first phase II study assessing the efficacy of the WEE1 inhibitor adavosertib with cisplatin in metastatic triple-negative breast cancer (mTNBC). Among patients with mTNBC treated with 0-1 prior lines, adavosertib combined with cisplatin narrowly missed the prespecified ORR cutoff of > 30%. The finding of immune infiltrated tumors in patients with clinical benefit to therapy requires validation in future studies.
Expand Down Expand Up @@ -43,8 +43,10 @@ data:
pubData=page.data
thumbnailDir=sectionId %}

## Available images
{:.mt-5}
<br>

## Narrated stories
{% include narrated-minerva-description.md %}

{% include atlas-dataset-cards.html
sectionId=sectionId
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