Blocking apoptosis promotes survival and alters developmental dynamics of human retinal ganglion cells in retinal organoids.
The 4 matches
- [1] § STAR★METHODS › METHOD DETAILS › Cell type annotation and transfer learning ↔ SZ_reproject_rename.py, lines 486–542 · score 0.89 · random forest classifier, max_features, n_estimators, probability, log, trained
- [2] § STAR★METHODS › METHOD DETAILS › Cell type annotation and transfer learning ↔ SZ_percabun_annotated.py, lines 201–255 · score 0.66 · chi squared, sz percabun annotated, cell
- [3] § STAR★METHODS › METHOD DETAILS › Library preparation and preprocessing ↔ SZ_PearsonNMF_Annotated.py, lines 1–30 · score 0.63 · Leiden clusters, regress, log, UMAP, matrixes, preprocessing
- [4] § STAR★METHODS › METHOD DETAILS › Pseudotime analysis of RGCs ↔ SZ_Plotter_Annotated.py, lines 66–68 · score 0.55 · score_genes, maturity score, Scanpy
Paper
Loaded from Europe PMC by your browser, not stored by OSCR: doi.org · Europe PMC
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The authors' code
Python · 576 lines · 13 KB · no license · 1 match
- #!/usr/bin/env python3
- import pandas as pd
- import seaborn as sns
- import numpy as np
- import scipy
- import anndata as ad
- import scanpy as sc
- from scipy.stats import chisquare
- from sklearn.decomposition import NMF
- import umap
- import statistics as stat
- import scipy.stats
- import scProject as scP
- import hdf5plugin
- # Modelling
- from sklearn.ensemble import RandomForestClassifier
- from sklearn.metrics import accuracy_score, confusion_matrix, precision_score, recall_score, ConfusionMatrixDisplay
- from sklearn.model_selection import RandomizedSearchCV, train_test_split
- from scipy.stats import randint
- print('importing done')
- #basic settings, from scanpy tutorial
- sc.settings.verbosity = 3 # verbosity: errors (0), warnings (1), info (2), hints (3)
- sc.logging.print_header()
- sc.settings.set_figure_params(dpi=80, facecolor="white")
- #%%
- #first we wrangle the chen data
- path ='Chen.h5ad'
- c_data = sc.read_h5ad(path)
- c_names = list(c_data.var_names)
- c_data.var['gene_id'] = c_names
- #%%
- path= "SZ_NMF_UMAP.h5ad"
- bg_data = sc.read_h5ad(path)
- b_names = list(bg_data.var_names)
- bg_data.var['gene_id'] = b_names
- #%%
- sc.pp.normalize_per_cell(bg_data)
- sc.pp.log1p(bg_data)
- print('beep boop')
- #%%
- #making my own matcher because scProject's is giving me a hard time
- matched = []
- unmatched = []
- c_match_bool = []
- count = 0
- for i in c_names:
- if i in b_names:
- matched.append( i )
- c_match_bool.append(True)
- else:
- unmatched.append( i )
- c_match_bool.append(False)
- c_data.var['Matched'] = c_match_bool
- print('before match')
- print(c_data)
- print('')
- matched = []
- unmatched = []
- b_match_bool = []
- count = 0
- for i in b_names:
- if i in c_names:
- matched.append( i )
- b_match_bool.append(True)
- else:
- unmatched.append( i )
- b_match_bool.append(False)
- bg_data.var['Matched'] = b_match_bool
- c_data = c_data[:, c_data.var["Matched"]]
- bg_data = bg_data[:,bg_data.var['Matched']]
- #%%
- ##########
- #processing bg data
- #########
- #basic filtering
- # define outliers and further filtering. We have excluded the suggested MT filtering.
- filtered_bgdata = bg_data.copy()
- print('here is bg filtered')
- print(filtered_bgdata)
- sc.pp.scale(bg_data)
- mins = bg_data.X.min()
- minval = abs(mins.min())
- bg_data.X = bg_data.X + minval
- #%%
- #Basic filtering of chen data
- #applying Pearson residuals
- sc.experimental.pp.highly_variable_genes(
- c_data, flavor="pearson_residuals", n_top_genes=3000)
- filtered_cdata = c_data.copy()
- #applying gene selection, maintaining just hvgs
- c_data = c_data[:, c_data.var["highly_variable"]]
- hvgs = c_data.var["highly_variable"]
- sc.pp.scale(c_data)
- #%%
- #now we start the NMF
- print('starting NMF')
- #Adjust if doing Pearson normalized, since NMF doesn't like negative numbers. whodathunkit.
- mins = c_data.X.min()
- minval = abs(mins.min())
- c_data.X = c_data.X + minval
- #convert X to DF, i dont think I do NMF within anndata
- prDF = c_data.to_df()
- genenames = list(prDF.columns.values)
- #number of components we will use for NMF
- comp = 40
- #naming outputDF columns
- colnam = []
- count = 1
- for i in range(0,comp):
- name = "NMF"
- name += str(count)
- colnam.append(name)
- count+= 1
- #actual NMF
- model = NMF(n_components=comp,
- init='random',
- random_state=0,
- verbose= 1,
- max_iter=10000)
- W = model.fit_transform(prDF)
- H = model.components_
- #%%
- #below returns pattern weights. This lets you know what genes are driving your NMF patterns (NRL could be a rod pattern driver, opsins for cones, etc)
- weightsDF = pd.DataFrame(H, columns = genenames)
- nmfDF= pd.DataFrame(data = W, columns = colnam )
- weightsAD = ad.AnnData(weightsDF)
- #weightsAD.write_h5ad('FetalPatterns.h5ad')
- weightsAD.write_h5ad('Fetal_BG_Patterns.h5ad')
- print('NMF is done')
- #%%
- ###########
- #actual transfer learning
- ###########
- print('')
- print('Transfer Learning started')
- matched_bg, patterns_filtered = scP.matcher.filterAnnDatas(bg_data, weightsAD, 'gene_id')
- scP.rg.NNLR_ElasticNet(matched_bg, patterns_filtered, 'fetalProject', alpha=.005, L1=.005)
- matched_chen, patterns_filtered = scP.matcher.filterAnnDatas(c_data, weightsAD, 'gene_id')
- scP.rg.NNLR_ElasticNet(matched_chen, patterns_filtered, 'fetalProject', alpha=.005, L1=.005)
- print('')
- print('Transfer Learning End')
- #%%
- print('')
- print('reassembling data')
- #assembling BG pattern space
- bg_pspace = matched_bg.obsm['fetalProject']
- nmfs = []
- for i in range(1,41):
- name = 'NMF'
- newname = name + str(i)
- nmfs.append(newname)
- cellname = []
- for i in range(0,len(bg_pspace)):
- name = 'bg_'
- newname = name + str(i)
- cellname.append(newname)
- bpat_df = pd.DataFrame(bg_pspace,columns = nmfs, index = cellname)
- #%%
- #assembling RC pattern space
- chen_pspace = matched_chen.obsm['fetalProject']
- cellname = []
- for i in range(0,len(chen_pspace)):
- name = 'chen_'
- newname = name + str(i)
- cellname.append(newname)
- cpat_df = pd.DataFrame(chen_pspace,columns = nmfs, index=cellname)
- for i in bpat_df.columns:
- bg_data.obs[i] = list(bpat_df[i].values)
- for i in cpat_df.columns:
- c_data.obs[i] = list(cpat_df[i].values)
- #%%
- bg_data.obs['Data_Source'] = 'BG_RA+/-'
- c_data.obs['Data_Source']= 'Chen_Fetal'
- #Ill make dummy columns so i can be more conservative with my concatenation
- c_data.obs['Day'] = 'N/A'
- c_data.obs['Genotype'] = 'Fetal'
- c_data.obs['Day/Genotype'] = 'N/A'
- c_data.obs['Manu_CT']= c_data.obs['majorclass']
- bg_data.obs['author_cell_type']='Organoid'
- bg_data.obs['majorclass'] = 'Organoid'
- bg_data.obs['subclass'] = 'Organoid'
- bg_data.obs['development_stage'] = 'N/A'
- cobs = c_data.obs
- bobs = bg_data.obs
- #%%
- print(cobs)
- #%%
- """
- cobs.to_csv('/Volumes/BGSEQFISH/Projecting_in_full/Partial_data/ChenObs_withPatterns.csv')
- bobs.to_csv('/Volumes/BGSEQFISH/Projecting_in_full/Partial_data/BG_Full_Obs_withPatterns.csv')
- """
- #%%
- #bringing back original count info. unfortunately the full dataset is too much for my machine to handle so im going to limit the count matrix to the top 15k hvgs from MY dataset.
- #applying Pearson residuals
- sc.experimental.pp.highly_variable_genes(
- filtered_bgdata, flavor="pearson_residuals", n_top_genes=15000)
- filtered_bgdata = filtered_bgdata[:,filtered_bgdata.var["highly_variable"]]
- #making my own matcher because scProject's is giving me a hard time
- c_names = list(filtered_cdata.var_names)
- b_names = list(filtered_bgdata.var_names)
- matched = []
- unmatched = []
- c_match_bool = []
- count = 0
- for i in c_names:
- if i in b_names:
- matched.append( i )
- c_match_bool.append(True)
- else:
- unmatched.append( i )
- c_match_bool.append(False)
- filtered_cdata.var['Matched'] = c_match_bool
- print('before match')
- print(c_data)
- print('')
- matched = []
- unmatched = []
- b_match_bool = []
- count = 0
- for i in b_names:
- if i in c_names:
- matched.append( i )
- b_match_bool.append(True)
- else:
- unmatched.append( i )
- b_match_bool.append(False)
- filtered_bgdata.var['Matched'] = b_match_bool
- filtered_cdata = filtered_cdata[:,filtered_cdata.var["Matched"]]
- filtered_bgdata = filtered_bgdata[:,filtered_bgdata.var['Matched']]
- #%%
- c_counts = filtered_cdata.X
- bg_counts = filtered_bgdata.X
- #%%
- fin_cdata = ad.AnnData( X = c_counts, obs = cobs)
- fin_cdata.var_names = filtered_cdata.var_names
- fin_bgdata = ad.AnnData(X = bg_counts, obs = bobs )
- fin_bgdata.var_names = filtered_bgdata.var_names
- #%%
- # %%
- #projecting my data into chen umap
- trans = umap.UMAP(n_neighbors=30, n_components=2, min_dist= 0.5, random_state=42).fit(cpat_df)
- test_embedding = trans.transform(bpat_df)
- fin_cdata.obsm['X_umap'] = trans.embedding_
- fin_bgdata.obsm['X_umap'] = test_embedding
- print('2D done')
- #%%
- #alrighty here is the randomforest classifier. first, for subclass
- adatas = [fin_cdata,fin_bgdata]
- data_big= ad.concat(adatas, join = 'inner')
- data_subclass = data_big.copy()
- sc.tl.rank_genes_groups(fin_cdata,
- groupby='subclass',
- n_genes=50,
- method= 'wilcoxon',
- )
- treatmentstow = fin_cdata.uns['rank_genes_groups']['names']
- print('markers found')
- genes = []
- for i in treatmentstow:
- for k in i:
- if k not in genes:
- genes.append(k)
- print('subsetting')
- class_gene_subset = []
- for i in data_subclass.var_names:
- if i in genes:
- class_gene_subset.append(True)
- else:
- class_gene_subset.append(False)
- data_subclass.var['Used_In_Classifier'] = class_gene_subset
- data_subclass = data_subclass[:,data_subclass.var['Used_In_Classifier']]
- print('here is the classifier data')
- print(data_subclass)
- ######
- rfc_chen= data_subclass[data_subclass.obs['Data_Source'] == 'Chen_Fetal']
- rfc_bg = data_subclass[data_subclass.obs['Data_Source'] == 'BG_RA+/-']
- rfc_chendf = rfc_chen.to_df()
- rfc_bgdf = rfc_bg.to_df()
- rfc_chendf['subclass'] = rfc_chen.obs['subclass']
- print('dfs made, training classifier')
- # Split the data into training and test sets
- X = rfc_chendf.drop('subclass', axis = 1)
- y = rfc_chendf['subclass']
- #X_train, X_test, y_train, y_test = train_test_split(X, y, test_size=0.2)
- #training the model
- rf = RandomForestClassifier(verbose= 3,n_jobs=16,n_estimators=200, random_state=13,max_features= None)
- rf.fit(X,y)
- print('predicting...')
- class_pred = rf.predict(rfc_bgdf)
- log_pred = rf.predict_log_proba(rfc_bgdf)
- prob_pred = rf.predict_proba(rfc_bgdf)
- max_logs = []
- for i in log_pred:
- realvals = []
- for k in i:
- if np.isneginf(k) == False:
- realvals.append(round(k,2))
- arr = np.array(realvals)
- maxi = arr.max()
- max_logs.append(maxi)
- maxprobs = []
- for i in prob_pred:
- maxi = i.max()
- maxprobs.append(maxi)
- print('outputting...')
- fin_bgdata.obs['RF_SubClass'] = class_pred
- fin_bgdata.obs['RF_SubClass_log']= max_logs
- fin_bgdata.obs['RF_SubClass_prob']= maxprobs
- fin_cdata.obs['RF_SubClass'] = list(fin_cdata.obs['subclass'].values)
- fin_cdata.obs['RF_SubClass_log']= 0
- fin_cdata.obs['RF_SubClass_prob'] = 1
- #perf. subclasses done. for ease of access, we are also gonna do a classifier on the majorclass
- data_majorclass = data_big.copy()
- sc.tl.rank_genes_groups(fin_cdata,
- groupby='majorclass',
- n_genes=50,
- method= 'wilcoxon',
- )
- treatmentstow = fin_cdata.uns['rank_genes_groups']['names']
- print('markers found')
- genes = []
- for i in treatmentstow:
- for k in i:
- if k not in genes:
- genes.append(k)
- print('subsetting')
- class_gene_subset = []
- for i in data_majorclass.var_names:
- if i in genes:
- class_gene_subset.append(True)
- else:
- class_gene_subset.append(False)
- data_majorclass.var['Used_In_Classifier'] = class_gene_subset
- data_majorclass = data_majorclass[:,data_majorclass.var['Used_In_Classifier']]
- print('here is the classifier data')
- print(data_majorclass)
- ######
- rfc_chen= data_majorclass[data_majorclass.obs['Data_Source'] == 'Chen_Fetal']
- rfc_bg = data_majorclass[data_majorclass.obs['Data_Source'] == 'BG_RA+/-']
- rfc_chendf = rfc_chen.to_df()
- rfc_bgdf = rfc_bg.to_df()
- rfc_chendf['majorclass'] = rfc_chen.obs['majorclass']
- print('dfs made, training classifier')
- # Split the data into training and test sets
- X = rfc_chendf.drop('majorclass', axis = 1)
- y = rfc_chendf['majorclass']
- #training the model
- rf = RandomForestClassifier(verbose= 3,n_jobs=16,n_estimators=200, random_state=13,max_features= None)
- rf.fit(X,y)
- print('predicting...')
- class_pred = rf.predict(rfc_bgdf)
- log_pred = rf.predict_log_proba(rfc_bgdf)
- prob_pred = rf.predict_proba(rfc_bgdf)
- max_logs = []
- for i in log_pred:
- realvals = []
- for k in i:
- if np.isneginf(k) == False:
- realvals.append(round(k,2))
- arr = np.array(realvals)
- maxi = arr.max()
- max_logs.append(maxi)
- maxprobs = []
- for i in prob_pred:
- maxi = i.max()
- maxprobs.append(maxi)
- print('outputting...')
- fin_bgdata.obs['RF_MajorClass'] = class_pred
- fin_bgdata.obs['RF_MajorClass_log']= max_logs
- fin_bgdata.obs['RF_MajorClass_prob']= maxprobs
- fin_cdata.obs['RF_MajorClass'] = list(fin_cdata.obs['majorclass'].values)
- fin_cdata.obs['RF_MajorClass_log']= 0
- fin_cdata.obs['RF_MajorClass_prob'] = 1
- fin_cdata.obs['Cell_Type'] = list(fin_cdata.obs['majorclass'].values)
- ct_id = []
- manu_calls= ['BSLC','RPE','Lens']
- manus = list(fin_bgdata.obs['Manu_CT'].values)
- rf_calls = list(fin_bgdata.obs['RF_MajorClass'].values)
- count = 0
- for i in manus:
- if i in manu_calls:
- ct_id.append(i)
- count += 1
- else:
- ct_id.append(rf_calls[count])
- count += 1
- fin_bgdata.obs['Cell_Type'] = ct_id
- #slapping these dudes together
- adatas = [fin_cdata,fin_bgdata]
- merged = ad.concat(adatas, join = 'inner')
- nmfDF = pd.DataFrame()
- for i in merged.obs.columns:
- if 'NMF' in i:
- nmfDF[i] = list(merged.obs[i].values)
- dr_adata = ad.AnnData(X = nmfDF)
- sc.pp.neighbors(dr_adata, n_pcs = 0)
- #sc.tl.umap(dr_adata)
- sc.tl.leiden(dr_adata,
- key_added= 'Leiden')
- merged.obs['Leiden'] = list(dr_adata.obs['Leiden'].values)
- print(merged)
- print(merged.obs)
- merged.write_h5ad('merged_SZ_Chen.h5ad')
- #%%
- #%%
SZ_reproject_rename.py at commit 53c99f4, no license · at the source
Overview
- Department of Biology, Johns Hopkins University, 3400 N. Charles Street, Baltimore, MD 21218, USA
- The Solomon H. Snyder Department of Neuroscience, Johns Hopkins Medical Institute, Baltimore, MD 21218, USA
- Division of Neonatology, Department of Pediatrics, Icahn School of Medicine at Mount Sinai, New York, NY 10029, USA
- Department of Otolaryngology, Icahn School of Medicine at Mount Sinai, New York, NY 10029, USA
- Department of Cell, Developmental, and Regenerative Biology, Icahn School of Medicine at Mount Sinai, New York, NY 10029, USA
- Institute for Airway Sciences, Icahn School of Medicine at Mount Sinai, New York, NY 10029, USA
- Institute for Regenerative Medicine, Icahn School of Medicine at Mount Sinai, New York, NY 10029, USA
- Lead contact
Abstract
Retinal ganglion cells (RGCs) are the projection neurons connecting the retina to the brain. In many species, a substantial proportion of RGCs are eliminated by programmed cell death during development to regulate their final number, but how cell death impacts human RGC development remains poorly understood. Here, we characterized cell death in human fetal retinas and retinal organoids. Both retinas and organoids exhibited two waves of apoptosis: an early wave targeting neurogenic retinal progenitor cells and neuronal precursors and a late wave affecting RGCs and other neurons. Additionally, organoids displayed a distinct wave of necrosis. Blocking apoptosis in organoids via BAX/
Reproduced under the paper's license (CC BY), from the paper cited above.
Repository
Its files are read in the Code ↔ Paper reader above, with 4 matches between paragraphs and lines of code.
BGuy2/SZ_BAX-BAKdKO
53c99f4a5f940fd43dae14fa7588dec27225d7bb, 16 September 2025Availability: 1 check, the latest on 29 September 2026: the link answers
- 29 September 2026: the link answers
10 files
- SZ_Heatmapexpression_ove
rpseudotime_Annotated.py , Python, 145 lines - SZ_PearsonNMF_Annotated.
py , Python, 221 lines, 1 match - SZ_Plotter_Annotated.py, Python, 345 lines, 1 match
- SZ_Pseudobulk_annotated.
py , Python, 300 lines - SZ_percabun_annotated.py
, Python, 363 lines, 1 match - SZ_pseudotime_annotated.
py , Python, 247 lines - SZ_reproject_rename.py, Python, 576 lines, 1 match
- SZ_supervisedUMAP.py, Python, 250 lines
- Wrangling_Firstfiles.py, Python, 118 lines
- README.md, Text, 12 lines
Tracing map
Proposed by the machine: these links were found in the paper and verified at the source, without human review. The map will receive a Zenodo DOI once one of the paper's authors has validated it with their ORCID.
What the map holds:
- 1 repository of the authors' code, each at its verified commit, with its license and how the link was found in the paper;
- 9 scripts, each with its path and the digest of its content;
- 4 matches between paragraphs of the paper and lines of the code (method lexical-v1);
- neither the text of the paper nor the code itself.
Its JSON (tracing-map.json) is deposited on Zenodo with its DOI once the map is validated.
Data
Datasets cited
- geo:GSE305194, at NCBI GEO; found in the resources table
Versions
The history of this record: each version stored by the harvester or made by a correction of its authors or of the maintainers of its code, and what changed in its facts. The texts of the paper (its abstract, its availability statements) are not part of it; versions that changed only those are not listed.
Version 1, 29 September 2026: the first record
Recorded: type, language, journal, volume, issue, pages, dates, 8 authors, 12 keywords, 5 funders, 128 references, 27 RRIDs.
Cite
This paper
Zhang, J. S., Guy, B., Santiago, C. P., Tiozzo, C., Sreenath, M., Chen, Y.-W., Blackshaw, S., & Johnston, R. J. (2026). Blocking apoptosis promotes survival and alters developmental dynamics of human retinal ganglion cells in retinal organoids. Cell reports, 45(4), 117270. https://
BibTeX
@article{zhang2026blocki
author = {Zhang, Jingliang Simon and Guy, Brian and Santiago, Clayton P and Tiozzo, Caterina and Sreenath, Meghana and Chen, Ya-Wen and Blackshaw, Seth and Johnston, Robert J},
title = {{Blocking apoptosis promotes survival and alters developmental dynamics of human retinal ganglion cells in retinal organoids}},
journal = {Cell reports},
year = {2026},
month = apr,
volume = {45},
number = {4},
pages = {117270},
publisher = {Cell Press},
issn = {2211-1247},
doi = {10.1016/
url = {https://
pmid = {41996242},
pmcid = {PMC13181862}
}
RIS
TY - JOUR
AU - Zhang, Jingliang Simon
AU - Guy, Brian
AU - Santiago, Clayton P
AU - Tiozzo, Caterina
AU - Sreenath, Meghana
AU - Chen, Ya-Wen
AU - Blackshaw, Seth
AU - Johnston, Robert J
TI - Blocking apoptosis promotes survival and alters developmental dynamics of human retinal ganglion cells in retinal organoids
T2 - Cell reports
J2 - Cell Rep
PY - 2026
DA - 2026/
VL - 45
IS - 4
SP - 117270
SN - 2211-1247
PB - Cell Press
DO - 10.1016/
UR - https://
LA - en
ER -
CSL-JSON
{
"id": "10.1016/
"type": "article-journal",
"title": "Blocking apoptosis promotes survival and alters developmental dynamics of human retinal ganglion cells in retinal organoids",
"container-title": "Cell reports",
"author": [
{
"family": "Zhang",
"given": "Jingliang Simon"
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{
"family": "Guy",
"given": "Brian"
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{
"family": "Santiago",
"given": "Clayton P"
},
{
"family": "Tiozzo",
"given": "Caterina"
},
{
"family": "Sreenath",
"given": "Meghana"
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{
"family": "Chen",
"given": "Ya-Wen"
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{
"family": "Johnston",
"given": "Robert J"
}
],
"container-title-short":
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"issue": "4",
"page": "117270",
"DOI": "10.1016/
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"ISSN": "2211-1247",
"publisher": "Cell Press",
"URL": "https://
"language": "en",
"issued": {
"date-parts": [
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}
}
The tracing map gets a citation of its own once an author has validated it and it has a DOI.
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