Corpus Engine Towards a reproducible .science file.
← All .science files

pmid:34681663

Proteomic Landscape of Extracellular Vesicles for Diffuse Large B-Cell Lymphoma Subtyping.

Ana Sofia Carvalho · Henrique Baeta · Andreia F A Henriques · Mostafa Ejtehadifar · Erin M Tranfield · Ana Laura Sousa · Ana Farinho · Bruno Costa Silva · José Cabeçadas · Paula Gameiro · Maria Gomes da Silva · Hans Christian Beck · Rune Matthiesen

International journal of molecular sciences · 2021 doi:10.3390/ijms222011004

Paper

complete

Experiment

complete

Data

partial

Analysis

complete

Execution

absent

Execution evidence has not yet been added to this .science file. Explore its methods, data and open questions to plan the next step.
Record details sci_version · id · kind · revision · content_hash · schema · created_at · updated_at · generator
id
pmid:34681663
kind
science-record
content_hash
sha256:5a4fed680db18cc77a7ac6a4af0fb8de481848fa671a32c4edcf04f1c28b8f48
schema
https://corpus.bntrg.co.uk/sci/1.0/sci.schema.json
created_at
2026-11-01T17:36:21Z
updated_at
2026-11-01T22:47:45Z
generator object · 2 fields
name
corpus-assay-engine
run_id
reading-sci-2026-11-01
paper object · 10 fields
state
complete
title
Proteomic Landscape of Extracellular Vesicles for Diffuse Large B-Cell Lymphoma Subtyping.
doi
10.3390/ijms222011004
pmid
34681663
authors array · 13 items
[0]
Ana Sofia Carvalho
[1]
Henrique Baeta
[2]
Andreia F A Henriques
[3]
Mostafa Ejtehadifar
[4]
Erin M Tranfield
[5]
Ana Laura Sousa
[6]
Ana Farinho
[7]
Bruno Costa Silva
[8]
José Cabeçadas
[9]
Paula Gameiro
[10]
Maria Gomes da Silva
[11]
Hans Christian Beck
[12]
Rune Matthiesen
journal
International journal of molecular sciences
year
2021
abstract
The role of extracellular vesicles (EVs) proteome in diffuse large B-cell lymphoma (DLBCL) pathology, subclassification, and patient screening is unexplored. We analyzed by state-of-the-art mass spectrometry the whole cell and secreted extracellular vesicles (EVs) proteomes of different molecular subtypes of DLBCL, germinal center B cell (GCB subtype), and activated B cell (ABC subtype). After quality control assessment, we compared whole-cell and secreted EVs proteomes of the two cell-of-origin (COO) categories, GCB and ABC subtypes, resulting in 288/1115 significantly differential expressed proteins from the whole-cell proteome and 228/608 proteins from EVs (adjust p-value < 0.05/p-value < 0.05). In our preclinical model system, we demonstrated that the EV proteome and the whole-cell proteome possess the capacity to separate cell lines into ABC and GCB subtypes. KEGG functional analysis and GO enrichment analysis for cellular component, molecular function, and biological process of differential expressed proteins (DEP) between ABC and GCB EVs showed a significant enrichment of pathways involved in immune response function. Other enriched functional categories for DEPs constitute cellular signaling and intracellular trafficking such as B-cell receptor (BCR), Fc_gamma R-mediated phagocytosis, ErbB signaling, and endocytosis. Our results suggest EVs can be explored as a tool for patient diagnosis, follow-up, and disease monitoring. Finally, this study proposes novel drug targets based on highly expressed proteins, for which antitumor drugs are available suggesting potential combinatorial therapies for aggressive forms of DLBCL. Data are available via ProteomeXchange with identifier PXD028267.
claims array · 3 items
[0] object · 6 fields
id
claim-method
statement
Protein label-free expression values were preprocessed by removing common MS contaminants followed by log2(x + 1) transformation, and quantile normalization. The quantitative values were all subjected to statistical analysis utilizing the R package limma [59] where contrast between ABC and GCB was specified (Table S1 whole cell and Table S2 for EVs). Correction for multiple testing was applied using the method of Benjamini and Hochberg [60].
kind
methodological
target
null
evidence array · 1 item
[0] object · 3 fields
asset
source:pmid:34681663
locator
sections[18] "4.8. Quantitative Analysis" paragraph 2
quote
Protein label-free expression values were preprocessed by removing common MS contaminants followed by log2(x + 1) transformation, and quantile normalization. The quantitative values were all subjected to statistical analysis utilizing the R package limma [59] where contrast between ABC and GCB was specified (Table S1 whole cell and Table S2 for EVs). Correction for multiple testing was applied using the method of Benjamini and Hochberg [60].
state
complete
[1] object · 6 fields
id
claim-data-access
statement
The mass spectrometry proteomics data have been deposited to the ProteomeXchange Consortium via the PRIDE [62] partner repository with the dataset identifier PXD028267.
kind
methodological
target
null
evidence array · 1 item
[0] object · 3 fields
asset
source:pmid:34681663
locator
sections[28] "Data Availability Statement" paragraph 2
quote
The mass spectrometry proteomics data have been deposited to the ProteomeXchange Consortium via the PRIDE [62] partner repository with the dataset identifier PXD028267.
state
complete
[2] object · 6 fields
id
claim-target-result
statement
The whole-cell and EV proteomes separated ABC from GCB DLBCL cell lines, with 288/1115 and 228/608 proteins differentially expressed, respectively.
kind
quantitative
target object · 4 fields
value
0.05
unit
p-value
tolerance
null
source
Statistical comparison between ABC and GCB quantitative proteomics data (Tables S1 and S2) revealed significance differences in 288/1115 expressed proteins (DEPs) from whole-cell proteome and 228/608 DEPs from EVs (adjust p-value < 0.05/p-value < 0.05).
evidence array · 2 items
[0] object · 3 fields
asset
source:pmid:34681663
locator
sections[6] "2.4. Multivariate Analysis of Quantitative MS Data" paragraph 2
quote
Statistical comparison between ABC and GCB quantitative proteomics data (Tables S1 and S2) revealed significance differences in 288/1115 expressed proteins (DEPs) from whole-cell proteome and 228/608 DEPs from EVs (adjust p-value < 0.05/p-value < 0.05).
[1] object · 3 fields
asset
source:pmid:34681663
locator
sections[6] "2.4. Multivariate Analysis of Quantitative MS Data" paragraph 2
quote
Principal component analysis using all quantitative data without any bias filtering of quantitative values showed separation of DLBCL into COO subtypes for both whole cell (Figure A2a) and EVs (Figure A2b).
state
complete
gaps array · 0 items
experiment object · 8 fields
state
complete
objective
The whole-cell and EV proteomes separated ABC from GCB DLBCL cell lines, with 288/1115 and 228/608 proteins differentially expressed, respectively.
steps array · 3 items
[0] object · 13 fields
id
read_published_estimate
order
1
name
Read the published estimate from the source
kind
other
state
complete
blocked_on
null
description
The claim, method and evidence span published with the source article.
parameters object · 0 fields
inputs array · 1 item
[0]
source:pmid:34681663
outputs array · 1 item
[0]
the published estimate and its evidence
instruments array · 0 items
reagents array · 0 items
[1] object · 13 fields
id
obtain_source_data
order
2
name
Obtain the source data from the named repository
kind
data-preparation
state
complete
blocked_on
null
description
The GEO series accession resolves and its sample accessions are listed. This lane did not download the dataset or read its licence.
parameters object · 0 fields
inputs array · 1 item
[0]
data:geo:PXD028267
outputs array · 1 item
[0]
the source data with its repository provenance
instruments array · 0 items
reagents array · 0 items
[2] object · 13 fields
id
run_analysis
order
3
name
Run the published analysis
kind
analysis
state
complete
blocked_on
null
description
Apply the paper's statistical method to the resolved series and compare the result with the published target.
parameters object · 0 fields
inputs array · 1 item
[0]
data:geo:PXD028267
outputs array · 1 item
[0]
the replicated result and its comparison
instruments array · 0 items
reagents array · 0 items
materials array · 0 items
instruments array · 0 items
reagents array · 0 items
conditions object · 0 fields
gaps array · 0 items
data object · 3 fields
state
partial
assets array · 2 items
[0] object · 15 fields
id
source:pmid:34681663
role
manuscript
format
xml
media_type
application/xml
uri
https://doi.org/10.3390/ijms222011004
sha256
sha256:9e5b1eaf497c4c994dad7c0223f75fef7c461a84343b27c5124c7c2bc909ee2e
bytes
66122
access
open
state
resolved
reader
null
reader_status
reader_required
identifier
10.3390/ijms222011004
version
null
note
Full article fetched from PMC; the checksum covers the rendered section body, not the original XML bytes.
structure object · 4 fields
pmcid
PMC8536203
source
europe_pmc_fulltext
coverage
whole_body
text_hash_scope
rendered_section_body
[1] object · 15 fields
id
data:geo:PXD028267
role
raw
format
geo-series
media_type
application/vnd.ncbi.geo-series+json
uri
https://www.ncbi.nlm.nih.gov/geo/query/acc.cgi?acc=PXD028267
sha256
null
bytes
null
access
open
state
resolved
reader
null
reader_status
reader_required
identifier
PXD028267
version
null
note
The mass spectrometry proteomics data have been deposited to the ProteomeXchange Consortium via the PRIDE [62] partner repository with the dataset identifier PXD028267.
structure object · 15 fields
repository
GEO
access_route
GEO accession URL
access_statement_verbatim
The mass spectrometry proteomics data have been deposited to the ProteomeXchange Consortium via the PRIDE [62] partner repository with the dataset identifier PXD028267.
access_statement_kind
data_availability_statement
sample_accessions array · 0 items
sample_count
null
group_sizes
null
group_sizes_basis
null
platform
null
taxon
null
title
Human Diffuse large B cell lymphoma cell lines
resolution_checked_at
2026-11-01T17:30:50Z
resolution_check
identifier_resolution_only_no_download_no_licence_read
downloaded
false
licence_read
false
gaps array · 2 items
[0]
asset:data:geo:PXD028267 not downloaded
[1]
asset:data:geo:PXD028267 licence not read
analysis object · 4 fields
state
complete
methods array · 3 items
[0] object · 10 fields
id
method-1
family
principal_component_analysis
specific
pca
label
Principal component analysis
dsl_operations array · 1 item
[0]
pca_fit
missing_operations array · 0 items
parameters object · 0 fields
data_shapes array · 1 item
[0]
wide_numeric_matrix
evidence object · 3 fields
score
1
band
verbatim
quote
Protein label-free expression values were preprocessed by removing common MS contaminants followed by log2(x + 1) transformation, and quantile normalization. The quantitative values were all subjected to statistical analysis utilizing the R package limma [59] where contrast between ABC and GCB was specified (Table S1 whole cell and Table S2 for EVs). Correction for multiple testing was applied using the method of Benjamini and Hochberg [60].
[1] object · 10 fields
id
method-2
family
differential_expression
specific
limma_voom
label
Differential expression analysis
dsl_operations array · 3 items
[0]
normalise_counts
[1]
differential_expression_fit
[2]
fdr_bh
missing_operations array · 0 items
parameters object · 0 fields
data_shapes array · 1 item
[0]
count_matrix_with_condition
evidence object · 3 fields
score
0.8
band
high
quote
limma
[2] object · 10 fields
id
method-3
family
network_analysis
specific
pathway_enrichment
label
Network / pathway analysis
dsl_operations array · 1 item
[0]
pathway_enrich
missing_operations array · 0 items
parameters object · 0 fields
data_shapes array · 1 item
[0]
edge_list
evidence object · 3 fields
score
0.7
band
medium
quote
GO enrichment
targets array · 1 item
[0] object · 8 fields
id
target-published-estimate
claim_id
claim-target-result
operation
differential_expression_fit
unit
p-value
tolerance
null
state
complete
note
The threshold the paper applied to its own result, as the paper states it. A run that reproduces the effect is judged against this threshold.
gaps array · 0 items
capability object · 3 fields
state
complete
requirements array · 1 item
[0] object · 6 fields
capability_id
capability:computational_analysis
label
Computational analysis platform
assay_families array · 9 items
[0]
meta_analysis
[1]
machine_learning
[2]
survival_analysis
[3]
statistical_regression
[4]
pca
[5]
molecular_docking
[6]
network_analysis
[7]
differential_expression
[8]
gwas
candidate
Automated Assays Laravel application and simulated adapters
gaps array · 0 items
readiness object · 8 fields
state
complete
tier
R1
blocked_on
nothing:replicable_now
axes object · 3 fields
method object · 5 fields
tier
R1
expressible
true
required_operations array · 1 item
[0]
pca_fit
missing_operations array · 0 items
basis
The paper names the method it used and the corpus's method extractor maps it onto the DSL catalogue: pca.
capability object · 4 fields
tier
R1
capability_id
capability:computational_analysis
availability_state
owned
basis
The computational analysis is owned. The physical bench the paper used is not, so a physical validation cannot be run here.
data object · 6 fields
tier
R1
reachable
true
accessions array · 1 item
[0]
PXD028267
resolved_accessions array · 1 item
[0]
PXD028267
statements array · 1 item
[0]
The mass spectrometry proteomics data have been deposited to the ProteomeXchange Consortium via the PRIDE [62] partner repository with the dataset identifier PXD028267.
basis
The paper names PXD028267 in ProteomeXchange Consortium via the PRIDE partner repository and the accession resolves in the repository. No dataset was downloaded and no licence was read.
can_run object · 3 fields
dsl_operations array · 1 item
[0]
pca_fit
assets array · 2 items
[0]
source:pmid:34681663
[1]
data:geo:PXD028267
steps array · 1 item
[0]
run_analysis
must_build object · 5 fields
dsl_operations array · 0 items
converters array · 0 items
readers array · 0 items
capabilities array · 0 items
data_gaps array · 1 item
[0]
data:geo:PXD028267
gaps array · 0 items
review object · 5 fields
state
partial
machine_critique object · 5 fields
kind
extraction_review
reader object · 5 fields
model
MiniMax-M3.1-Flash
provider
minimax
provider_family
minimax
read_at
2026-11-01T17:04:47Z
independence
single_reader
evidence_check object · 2 fields
method
verbatim
availability
verbatim
calls
5
usage object · 3 fields
prompt_tokens
18447
completion_tokens
1525
cached_tokens
128
stages array · 1 item
[0] object · 4 fields
id
extraction
state
complete
reader
MiniMax-M3.1-Flash
provider
minimax
gaps array · 3 items
[0]
review.independent_reader
[1]
review.machine_critique
[2]
review.human_critique
execution object · 5 fields
state
absent
status
not_run
mode
null
runs array · 0 items
gaps array · 1 item
[0]
execution.not_run
provenance object · 7 fields
entities array · 3 items
[0] object · 3 fields
id
pmid:34681663
type
paper
label
pmid:34681663
[1] object · 3 fields
id
source:pmid:34681663
type
manuscript
label
PMID 34681663 full text
[2] object · 3 fields
id
data:geo:PXD028267
type
dataset
label
GEO PXD028267
activities array · 3 items
[0] object · 4 fields
id
activity-reading-sci-2026-11-01
type
classification
used array · 3 items
[0] object · 3 fields
id
pmid:34681663
type
paper
label
pmid:34681663
[1] object · 3 fields
id
source:pmid:34681663
type
manuscript
label
PMID 34681663 full text
[2] object · 3 fields
id
data:geo:PXD028267
type
dataset
label
GEO PXD028267
agent
agent:corpus-assay-engine
[1] object · 4 fields
id
activity-read-34681663
type
extraction
used array · 1 item
[0]
source:pmid:34681663
agent
agent:minimax-reader
[2] object · 4 fields
id
activity-resolve-PXD028267
type
accession_resolution
used array · 1 item
[0]
data:geo:PXD028267
agent
agent:corpus-assay-engine
agents array · 2 items
[0] object · 3 fields
id
agent:corpus-assay-engine
type
software
label
Corpus assay engine
[1] object · 3 fields
id
agent:minimax-reader
type
software
label
MiniMax literature reader
source_run_id
reading-sci-2026-11-01
dsl_catalogue_fingerprint
343fb30756ba6ec3
capability_table_fingerprint
2cb3e42f047d2ecf
snapshot_id
ba34b49490d9bfaf
lineage object · 4 fields
parent_id
pmid:34681663
parent_hash
sha256:2b6cd6cc49e8bef89b29378d80e6b16df6082bb93a388d2578d3efd7c9bd72b1
fork_of
null
gaps array · 6 items
[0]
asset:data:geo:PXD028267 licence not read
[1]
asset:data:geo:PXD028267 not downloaded
[2]
execution.not_run
[3]
review.human_critique
[4]
review.independent_reader
[5]
review.machine_critique
assays array · 2 items
[0] object · 11 fields
role
data_generation
definition_id
mass_spectrometry
definition_version
99e1195c7d6f
required_operations array · 0 items
support_state
partial
source_hashes object · 1 field
assay_lexicon
99e1195c7d6f
confidence
0.99
evidence array · 3 items
[0]
Proteomic Landscape of Extracellular Vesicles for Diff
[1]
comparison between ABC and GCB quantitative proteomics data (Tables S1 and S2) revealed significanc
[2]
unexplored. We analyzed by state-of-the-art mass spectrometry the whole cell and secreted extracellular ve
order_basis
paper_text_order:0
id
assay:1
[1] object · 11 fields
role
analysis
definition_id
principal_component_analysis
definition_version
f2132e96ae6c7a4e
required_operations array · 1 item
[0]
pca_fit
support_state
supported
source_hashes object · 1 field
dsl_catalogue
f2132e96ae6c7a4e
evidence array · 1 item
[0]
Protein label-free expression values were preprocessed by removing common MS contaminants followed by log2(x + 1) transformation, and quantile normalization. The quantitative values were all subjected to statistical analysis utilizing the R package limma [59] where contrast between ABC and GCB was specified (Table S1 whole cell and Table S2 for EVs). Correction for multiple testing was applied using the method of Benjamini and Hochberg [60].
order_basis
consumes_earlier_output
id
assay:2
Complete file
{"sci_version": "1.2", "schema": "https://corpus.bntrg.co.uk/sci/1.0/sci.schema.json", "id": "pmid:34681663", "kind": "science-record", "revision": 5, "content_hash": "sha256:5a4fed680db18cc77a7ac6a4af0fb8de481848fa671a32c4edcf04f1c28b8f48", "created_at": "2026-11-01T17:36:21Z", "updated_at": "2026-11-01T22:47:45Z", "generator": {"name": "corpus-assay-engine", "run_id": "reading-sci-2026-11-01"}, "paper": {"state": "complete", "title": "Proteomic Landscape of Extracellular Vesicles for Diffuse Large B-Cell Lymphoma Subtyping.", "doi": "10.3390/ijms222011004", "pmid": "34681663", "authors": ["Ana Sofia Carvalho", "Henrique Baeta", "Andreia F A Henriques", "Mostafa Ejtehadifar", "Erin M Tranfield", "Ana Laura Sousa", "Ana Farinho", "Bruno Costa Silva", "José Cabeçadas", "Paula Gameiro", "Maria Gomes da Silva", "Hans Christian Beck", "Rune Matthiesen"], "journal": "International journal of molecular sciences", "year": 2021, "abstract": "The role of extracellular vesicles (EVs) proteome in diffuse large B-cell lymphoma (DLBCL) pathology, subclassification, and patient screening is unexplored. We analyzed by state-of-the-art mass spectrometry the whole cell and secreted extracellular vesicles (EVs) proteomes of different molecular subtypes of DLBCL, germinal center B cell (GCB subtype), and activated B cell (ABC subtype). After quality control assessment, we compared whole-cell and secreted EVs proteomes of the two cell-of-origin (COO) categories, GCB and ABC subtypes, resulting in 288/1115 significantly differential expressed proteins from the whole-cell proteome and 228/608 proteins from EVs (adjust p-value < 0.05/p-value < 0.05). In our preclinical model system, we demonstrated that the EV proteome and the whole-cell proteome possess the capacity to separate cell lines into ABC and GCB subtypes. KEGG functional analysis and GO enrichment analysis for cellular component, molecular function, and biological process of differential expressed proteins (DEP) between ABC and GCB EVs showed a significant enrichment of pathways involved in immune response function. Other enriched functional categories for DEPs constitute cellular signaling and intracellular trafficking such as B-cell receptor (BCR), Fc_gamma R-mediated phagocytosis, ErbB signaling, and endocytosis. Our results suggest EVs can be explored as a tool for patient diagnosis, follow-up, and disease monitoring. Finally, this study proposes novel drug targets based on highly expressed proteins, for which antitumor drugs are available suggesting potential combinatorial therapies for aggressive forms of DLBCL. Data are available via ProteomeXchange with identifier PXD028267.", "claims": [{"id": "claim-method", "statement": "Protein label-free expression values were preprocessed by removing common MS contaminants followed by log2(x + 1) transformation, and quantile normalization. The quantitative values were all subjected to statistical analysis utilizing the R package limma [59] where contrast between ABC and GCB was specified (Table S1 whole cell and Table S2 for EVs). Correction for multiple testing was applied using the method of Benjamini and Hochberg [60].", "kind": "methodological", "target": null, "evidence": [{"asset": "source:pmid:34681663", "locator": "sections[18] \"4.8. Quantitative Analysis\" paragraph 2", "quote": "Protein label-free expression values were preprocessed by removing common MS contaminants followed by log2(x + 1) transformation, and quantile normalization. The quantitative values were all subjected to statistical analysis utilizing the R package limma [59] where contrast between ABC and GCB was specified (Table S1 whole cell and Table S2 for EVs). Correction for multiple testing was applied using the method of Benjamini and Hochberg [60]."}], "state": "complete"}, {"id": "claim-data-access", "statement": "The mass spectrometry proteomics data have been deposited to the ProteomeXchange Consortium via the PRIDE [62] partner repository with the dataset identifier PXD028267.", "kind": "methodological", "target": null, "evidence": [{"asset": "source:pmid:34681663", "locator": "sections[28] \"Data Availability Statement\" paragraph 2", "quote": "The mass spectrometry proteomics data have been deposited to the ProteomeXchange Consortium via the PRIDE [62] partner repository with the dataset identifier PXD028267."}], "state": "complete"}, {"id": "claim-target-result", "statement": "The whole-cell and EV proteomes separated ABC from GCB DLBCL cell lines, with 288/1115 and 228/608 proteins differentially expressed, respectively.", "kind": "quantitative", "target": {"value": 0.05, "unit": "p-value", "tolerance": null, "source": "Statistical comparison between ABC and GCB quantitative proteomics data (Tables S1 and S2) revealed significance differences in 288/1115 expressed proteins (DEPs) from whole-cell proteome and 228/608 DEPs from EVs (adjust p-value < 0.05/p-value < 0.05)."}, "evidence": [{"asset": "source:pmid:34681663", "locator": "sections[6] \"2.4. Multivariate Analysis of Quantitative MS Data\" paragraph 2", "quote": "Statistical comparison between ABC and GCB quantitative proteomics data (Tables S1 and S2) revealed significance differences in 288/1115 expressed proteins (DEPs) from whole-cell proteome and 228/608 DEPs from EVs (adjust p-value < 0.05/p-value < 0.05)."}, {"asset": "source:pmid:34681663", "locator": "sections[6] \"2.4. Multivariate Analysis of Quantitative MS Data\" paragraph 2", "quote": "Principal component analysis using all quantitative data without any bias filtering of quantitative values showed separation of DLBCL into COO subtypes for both whole cell (Figure A2a) and EVs (Figure A2b)."}], "state": "complete"}], "gaps": []}, "experiment": {"state": "complete", "objective": "The whole-cell and EV proteomes separated ABC from GCB DLBCL cell lines, with 288/1115 and 228/608 proteins differentially expressed, respectively.", "steps": [{"id": "read_published_estimate", "order": 1, "name": "Read the published estimate from the source", "kind": "other", "state": "complete", "blocked_on": null, "description": "The claim, method and evidence span published with the source article.", "duration_hours": null, "parameters": {}, "inputs": ["source:pmid:34681663"], "outputs": ["the published estimate and its evidence"], "instruments": [], "reagents": []}, {"id": "obtain_source_data", "order": 2, "name": "Obtain the source data from the named repository", "kind": "data-preparation", "state": "complete", "blocked_on": null, "description": "The GEO series accession resolves and its sample accessions are listed. This lane did not download the dataset or read its licence.", "duration_hours": null, "parameters": {}, "inputs": ["data:geo:PXD028267"], "outputs": ["the source data with its repository provenance"], "instruments": [], "reagents": []}, {"id": "run_analysis", "order": 3, "name": "Run the published analysis", "kind": "analysis", "state": "complete", "blocked_on": null, "description": "Apply the paper's statistical method to the resolved series and compare the result with the published target.", "duration_hours": null, "parameters": {}, "inputs": ["data:geo:PXD028267"], "outputs": ["the replicated result and its comparison"], "instruments": [], "reagents": []}], "materials": [], "instruments": [], "reagents": [], "conditions": {}, "gaps": []}, "data": {"state": "partial", "assets": [{"id": "source:pmid:34681663", "role": "manuscript", "format": "xml", "media_type": "application/xml", "uri": "https://doi.org/10.3390/ijms222011004", "sha256": "sha256:9e5b1eaf497c4c994dad7c0223f75fef7c461a84343b27c5124c7c2bc909ee2e", "bytes": 66122, "access": "open", "state": "resolved", "reader": null, "reader_status": "reader_required", "identifier": "10.3390/ijms222011004", "version": null, "note": "Full article fetched from PMC; the checksum covers the rendered section body, not the original XML bytes.", "structure": {"pmcid": "PMC8536203", "source": "europe_pmc_fulltext", "coverage": "whole_body", "text_hash_scope": "rendered_section_body"}}, {"id": "data:geo:PXD028267", "role": "raw", "format": "geo-series", "media_type": "application/vnd.ncbi.geo-series+json", "uri": "https://www.ncbi.nlm.nih.gov/geo/query/acc.cgi?acc=PXD028267", "sha256": null, "bytes": null, "access": "open", "state": "resolved", "reader": null, "reader_status": "reader_required", "identifier": "PXD028267", "version": null, "note": "The mass spectrometry proteomics data have been deposited to the ProteomeXchange Consortium via the PRIDE [62] partner repository with the dataset identifier PXD028267.", "structure": {"repository": "GEO", "access_route": "GEO accession URL", "access_statement_verbatim": "The mass spectrometry proteomics data have been deposited to the ProteomeXchange Consortium via the PRIDE [62] partner repository with the dataset identifier PXD028267.", "access_statement_kind": "data_availability_statement", "sample_accessions": [], "sample_count": null, "group_sizes": null, "group_sizes_basis": null, "platform": null, "taxon": null, "title": "Human Diffuse large B cell lymphoma cell lines", "resolution_checked_at": "2026-11-01T17:30:50Z", "resolution_check": "identifier_resolution_only_no_download_no_licence_read", "downloaded": false, "licence_read": false}}], "gaps": ["asset:data:geo:PXD028267 not downloaded", "asset:data:geo:PXD028267 licence not read"]}, "analysis": {"state": "complete", "methods": [{"id": "method-1", "family": "principal_component_analysis", "specific": "pca", "label": "Principal component analysis", "dsl_operations": ["pca_fit"], "missing_operations": [], "expressible": true, "parameters": {}, "data_shapes": ["wide_numeric_matrix"], "evidence": {"score": 1.0, "band": "verbatim", "quote": "Protein label-free expression values were preprocessed by removing common MS contaminants followed by log2(x + 1) transformation, and quantile normalization. The quantitative values were all subjected to statistical analysis utilizing the R package limma [59] where contrast between ABC and GCB was specified (Table S1 whole cell and Table S2 for EVs). Correction for multiple testing was applied using the method of Benjamini and Hochberg [60]."}}, {"id": "method-2", "family": "differential_expression", "specific": "limma_voom", "label": "Differential expression analysis", "dsl_operations": ["normalise_counts", "differential_expression_fit", "fdr_bh"], "missing_operations": [], "expressible": true, "parameters": {}, "data_shapes": ["count_matrix_with_condition"], "evidence": {"score": 0.8, "band": "high", "quote": "limma"}}, {"id": "method-3", "family": "network_analysis", "specific": "pathway_enrichment", "label": "Network / pathway analysis", "dsl_operations": ["pathway_enrich"], "missing_operations": [], "expressible": true, "parameters": {}, "data_shapes": ["edge_list"], "evidence": {"score": 0.7, "band": "medium", "quote": "GO enrichment"}}], "targets": [{"id": "target-published-estimate", "claim_id": "claim-target-result", "operation": "differential_expression_fit", "expected_value": 0.05, "unit": "p-value", "tolerance": null, "state": "complete", "note": "The threshold the paper applied to its own result, as the paper states it. A run that reproduces the effect is judged against this threshold."}], "gaps": []}, "capability": {"state": "complete", "requirements": [{"capability_id": "capability:computational_analysis", "label": "Computational analysis platform", "assay_families": ["meta_analysis", "machine_learning", "survival_analysis", "statistical_regression", "pca", "molecular_docking", "network_analysis", "differential_expression", "gwas"], "availability_state": "owned", "tier_unlocked": "R1", "candidate": "Automated Assays Laravel application and simulated adapters"}], "gaps": []}, "readiness": {"state": "complete", "tier": "R1", "blocking_axis": "none", "blocked_on": "nothing:replicable_now", "axes": {"method": {"tier": "R1", "expressible": true, "required_operations": ["pca_fit"], "missing_operations": [], "basis": "The paper names the method it used and the corpus's method extractor maps it onto the DSL catalogue: pca."}, "capability": {"tier": "R1", "capability_id": "capability:computational_analysis", "availability_state": "owned", "basis": "The computational analysis is owned. The physical bench the paper used is not, so a physical validation cannot be run here."}, "data": {"tier": "R1", "reachable": true, "accessions": ["PXD028267"], "resolved_accessions": ["PXD028267"], "statements": ["The mass spectrometry proteomics data have been deposited to the ProteomeXchange Consortium via the PRIDE [62] partner repository with the dataset identifier PXD028267."], "basis": "The paper names PXD028267 in ProteomeXchange Consortium via the PRIDE partner repository and the accession resolves in the repository. No dataset was downloaded and no licence was read."}}, "can_run": {"dsl_operations": ["pca_fit"], "assets": ["source:pmid:34681663", "data:geo:PXD028267"], "steps": ["run_analysis"]}, "must_build": {"dsl_operations": [], "converters": [], "readers": [], "capabilities": [], "data_gaps": ["data:geo:PXD028267"]}, "gaps": []}, "review": {"state": "partial", "machine_critique": {"kind": "extraction_review", "reader": {"model": "MiniMax-M3.1-Flash", "provider": "minimax", "provider_family": "minimax", "read_at": "2026-11-01T17:04:47Z", "independence": "single_reader"}, "evidence_check": {"method": "verbatim", "availability": "verbatim"}, "calls": 5, "usage": {"prompt_tokens": 18447, "completion_tokens": 1525, "cached_tokens": 128}}, "human_critique": null, "stages": [{"id": "extraction", "state": "complete", "reader": "MiniMax-M3.1-Flash", "provider": "minimax"}], "gaps": ["review.independent_reader", "review.machine_critique", "review.human_critique"]}, "execution": {"state": "absent", "status": "not_run", "mode": null, "runs": [], "gaps": ["execution.not_run"]}, "provenance": {"entities": [{"id": "pmid:34681663", "type": "paper", "label": "pmid:34681663"}, {"id": "source:pmid:34681663", "type": "manuscript", "label": "PMID 34681663 full text"}, {"id": "data:geo:PXD028267", "type": "dataset", "label": "GEO PXD028267"}], "activities": [{"id": "activity-reading-sci-2026-11-01", "type": "classification", "used": [{"id": "pmid:34681663", "type": "paper", "label": "pmid:34681663"}, {"id": "source:pmid:34681663", "type": "manuscript", "label": "PMID 34681663 full text"}, {"id": "data:geo:PXD028267", "type": "dataset", "label": "GEO PXD028267"}], "agent": "agent:corpus-assay-engine"}, {"id": "activity-read-34681663", "type": "extraction", "used": ["source:pmid:34681663"], "agent": "agent:minimax-reader"}, {"id": "activity-resolve-PXD028267", "type": "accession_resolution", "used": ["data:geo:PXD028267"], "agent": "agent:corpus-assay-engine"}], "agents": [{"id": "agent:corpus-assay-engine", "type": "software", "label": "Corpus assay engine"}, {"id": "agent:minimax-reader", "type": "software", "label": "MiniMax literature reader"}], "source_run_id": "reading-sci-2026-11-01", "dsl_catalogue_fingerprint": "343fb30756ba6ec3", "capability_table_fingerprint": "2cb3e42f047d2ecf", "snapshot_id": "ba34b49490d9bfaf"}, "lineage": {"parent_id": "pmid:34681663", "parent_hash": "sha256:2b6cd6cc49e8bef89b29378d80e6b16df6082bb93a388d2578d3efd7c9bd72b1", "fork_of": null, "generation": 4}, "gaps": ["asset:data:geo:PXD028267 licence not read", "asset:data:geo:PXD028267 not downloaded", "execution.not_run", "review.human_critique", "review.independent_reader", "review.machine_critique"], "assays": [{"role": "data_generation", "definition_id": "mass_spectrometry", "definition_version": "99e1195c7d6f", "definition_digest": null, "required_operations": [], "support_state": "partial", "source_hashes": {"assay_lexicon": "99e1195c7d6f"}, "confidence": 0.99, "evidence": ["Proteomic Landscape of Extracellular Vesicles for Diff", "comparison between ABC and GCB quantitative proteomics data (Tables S1 and S2) revealed significanc", "unexplored. We analyzed by state-of-the-art mass spectrometry the whole cell and secreted extracellular ve"], "order_basis": "paper_text_order:0", "id": "assay:1"}, {"role": "analysis", "definition_id": "principal_component_analysis", "definition_version": "f2132e96ae6c7a4e", "definition_digest": null, "required_operations": ["pca_fit"], "support_state": "supported", "source_hashes": {"dsl_catalogue": "f2132e96ae6c7a4e"}, "confidence": 1.0, "evidence": ["Protein label-free expression values were preprocessed by removing common MS contaminants followed by log2(x + 1) transformation, and quantile normalization. The quantitative values were all subjected to statistical analysis utilizing the R package limma [59] where contrast between ABC and GCB was specified (Table S1 whole cell and Table S2 for EVs). Correction for multiple testing was applied using the method of Benjamini and Hochberg [60]."], "order_basis": "consumes_earlier_output", "id": "assay:2"}]}