Comprehensive Integration of Single-Cell Data
Cell, 2019 · paper · Biomedicine
Develops a strategy that "anchors" single-cell datasets together to integrate measurements across RNA-sequencing technologies and across modalities. It reports improvement over existing methods and applies it to chromatin accessibility, protein expression and spatial gene expression data.
Checked: PDF from europepmc.org, fetched 4 Oct 2026. Page numbers are those of that PDF.
11 findings
Substance The Figure 4A legend gives 'a CITE-seq dataset of 35,543 bone marrow cells and 25 surface proteins'. The Results (p10), Methods (p24, p25) and Fig. 4F axis ('33,454 cell in-house dataset') give 33,454 for the same dataset.
- p. 46 Figure 4 legend (A)
dataset of 35,543 bone marrow cells and 25 surface proteins
- p. 10 Results, Predicting protein expression
capturing 33,454 cells
- p. 24 CITE-seq cross-validation
We separated the 33,454-cell CITE-seq dataset
- p. 46 Figure 4F y-axis
33,454 cell in-house dataset
Judge's note: A search of the text finds 35,543 only in the legend. The Methods cross-validation section explicitly uses 'the 33,454-cell CITE-seq dataset', and the Fig. 4F axis on the same figure reads 33,454. No second (e.g., pre-QC) count is defined anywhere.
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Reference or label Reference entry "Gavin K, Stegle O, Reik W, 2017 Single-cell epigenomics: Recording the past and predicting the future. Science 358 (6359), 60–75." lists the first author as 'Gavin K', and the text cites it as 'Gavin et al., 2017'.
- p. 2 Introduction, para 1
[Luo et al., 2018, Gavin et al., 2017]
- p. 14 Discussion, para 3
Gavin et al., 2017, Cao et al., 2018
- p. 34 Reference list
Gavin K, Stegle O, Reik W, 2017 Single-cell epigenomics
Only the authors can say what is right here.
Judge's note: Rests on outside knowledge: the first author of this Science 2017 review is Gavin Kelsey (surname Kelsey), so the entry should read 'Kelsey G' and the in-text citations 'Kelsey et al., 2017'. The page 34 image shows the entry exactly as quoted, and pages 2 and 14 cite it as 'Gavin et al., 2017'. I did not judge the page range.
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Reference or label The bipolar-cell benchmark is cited as "(Figure 2J,K; Figure S1E,F)", but Figure 2J is the pancreas anchor-count bar chart. The bipolar metrics are in panels K and L.
- p. 6 Results, para 3
(Figure 2J,K; Figure S1E,F)
- p. 43 Figure 2 panels/legend
(I-J) Distribution of anchor scores and counts
- p. 6 Results, concluding sentences of benchmark paragraph
effects[Shekhar et al., 2016] (Figure 2J,K; Figure S1E,F)
- p. 6 Results, preceding sentence
highest silhouette scores and performed well on all other metrics (Figure 2K,L)
Judge's note: In the Figure 2 image (p43), panel J is a bar chart of Incorrect vs Correct anchor counts, and the legend ties panels I-J to the anchors from Figure S1A. Panel K (silhouette) and panel L (mixing/local structure) each contain a 'bipolar' group. The sentence just before correctly cites 'Figure 2K,L'.
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Reference or label The text cites "subset-specific markers (Pvalb, Sst, Vip, Id2; Figure 3F)" and the legend gives a y-axis maximum for "Id2", but Figure 3F shows no Id2 locus. The seven loci shown are Neurod6, Gad2, Lhx6, Vip, Lamp5, Sst and Pvalb.
- p. 8 Results, scATAC paragraph
(Pvalb, Sst, Vip, Id2; Figure 3F)
- p. 45 Figure 3F legend
Gad2, Pvalb, Sst, Vip, Lamp5, and Id2 1,000
- p. 44 Figure 3F panel loci
Neurod6 Gad2 Lhx6 Vip Lamp5 Sst Pvalb
Only the authors can say what is right here.
Judge's note: In Figure 3F (p44) the locus labels are Neurod6, Gad2, Lhx6, Vip, Lamp5, Sst and Pvalb. The legend (p45) lists maxima for eight loci, including both Lamp5 and Id2. The text (p8) names Id2 and leaves out Lamp5. Only the authors can say whether Id2 was meant to be shown or whether the Lamp5 locus stands in for the Lamp5/Id2 class.
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Reference or label The Key Resources Table row 'Mouse prefrontal cortex – SMART-seq2' (Allen Institute, .../well_known_file_download/694413985) mislabels the Allen SMART-seq2 data, which the text describes as mouse visual cortex.
- p. 51 Key resources table, Deposited data
Mouse prefrontal cortex – SMART-seq2
- p. 23 Data Acquisition
The mouse visual cortex SMART-seq2 data was obtained from the Allen Brain Data Portal
- p. 8 Results, Projecting cellular states across modalities
of the mouse visual cortex from the Allen Brain Atlas
- p. 12 Results, Spatial mapping
two complementary datasets of the mouse visual cortex
Judge's note: Page 23 says 'The mouse visual cortex SMART-seq2 data was obtained from the Allen Brain Data Portal [Institute, 2018...]', and that reference (p35) has the same URL ending in 694413985. Prefrontal cortex is the scATAC-seq tissue. Separately, the table on p52 gives the GOstats v2.44.0 row the deepTools GitHub URL. The GEOXXXXXX placeholder is handled in C045.
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Reference or label Methods say cells were incubated 'with a pool of 25 antibodies' (and Fig 4 legend says '25 surface proteins'), but the Antibody List (p.24) and Key Resources Table (p.50) each name only 24 non-hashtag antibodies; CD278-ICOS, plotted in Fig 4B, is in neither list.
- p. 23 Methods, CITE-seq experiment
incubated with a pool of 25 antibodies
- p. 24 Antibody List
The following human Totalseq BioLegend antibodies were included in the pool
- p. 50 Key resources table, Antibodies
CD34
- p. 46 Figure 4B y-axis
CD278−ICOS
Only the authors can say what is right here.
Judge's note: I counted the p.24 list and the p.50 table (upright image). Both give 24 targets: CD3, CD56, CD19, CD11c, CD38, CD45RA, CD123, CD127, CD4, CD8a, CD14, CD16, CD25, CD45RO, CD69, CD197, CD161, CD28, CD27, HLA-DR, CD57, CD79b, CD11a and CD34. The Fig 4B y-axis has 25 imputed ADTs, one of which is CD278-ICOS. The hashtags are listed separately, so they do not explain the difference. The ICOS reagent is missing from both lists.
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Reference or label The CD56 TotalSeq antibody has catalogue number 'CD56 (cat #: 362557)' in the Methods Antibody List (p.24) but 'Cat# 363557' in the Key Resources Table (p.50).
- p. 24 Antibody List
CD56 (cat #: 362557)
- p. 50 Key resources table
Cat# 363557
- p. 50 Key resources table
CD56 BioLegend Cat# 363557
Only the authors can say what is right here.
Judge's note: Both page images show the two different numbers for the single CD56 reagent in the pool. The files do not show which one is correct.
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Reference or label The CITE-seq preprocessing methods (p.24) say transcripts were quantified 'using CellRanger v2.1.0', while the Key Resources Table (p.52) lists 'CellRanger v2.2.0'.
- p. 24 CITE-seq data preprocessing
CellRanger v2.1.0
- p. 52 Key resources table, Software
CellRanger v2.2.0
Only the authors can say what is right here.
Judge's note: I checked both images. CellRanger is mentioned only in these two places (grep), so the version mismatch cannot be put down to different datasets.
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Reference or label The Key Resources Table lists 'Human bone marrow – CITE-seq | This paper | GEOXXXXXX', an unfilled placeholder, while Data and software availability gives 'GEO (GSE128639)'.
- p. 51 Key resources table, Deposited data
GEOXXXXXX
- p. 33 Data and software availability
GEO (GSE128639)
- p. 33 Data and software availability
processed expression matrices through GEO (GSE128639)
- p. 33 Data availability
GSE128639
Judge's note: Seen in the table on p51 and the availability text on p33.
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Reference or label The Okhrimenko et al. 2014 entry cites 'PNAS 111 (25), 9229–9234' but gives the URL 'http://ard.bmj.com/lookup/doi/10.1136/annrheumdis-2013-205124.184' (p36).
- p. 36 Reference list
lookup/doi/10.1136/annrheumdis-2013-205124.184
Only the authors can say what is right here.
Judge's note: Rests on outside knowledge: that ard.bmj.com / 10.1136/annrheumdis is the Annals of the Rheumatic Diseases and not PNAS. The image shows the PNAS citation and the ard.bmj.com URL in the same entry. The URL's domain and DOI prefix do not match the journal named.
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Reference or label In the Key Resources Table, the identifier for "GOstats v2.44.0" (Falcon and Gentleman, 2007) is "https://github.com/deeptools/deepTools", the same URL as the deepTools v3.1.2 row directly above it.
- p. 52 Key resources table, Software
GOstats v2.44.0
Judge's note: I checked the upright page 52 image. The GOstats row lists https://github.com/deeptools/deepTools, the same URL as the deepTools row above it. That repository is the deepTools project, not a GOstats source, so the URL looks copied from the row above. GOstats is used in the Methods (text line ~1194, citing Falcon and Gentleman, 2007). The CITE-seq accession placeholder that one reviewer also raised is a separate point and is not judged here.
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30 minor (typos and the like; most checked by the judge only)
Wording The Fig. 3E legend says anchors were found between 'scRNA-seq data (reference) and a gene activity matrix derived from scATAC-seq (query) datasets from the mouse visual cortex', yet the Methods (p29) and Data Acquisition (p23) give the scATAC-seq as mouse prefrontal cortex.
- p. 45 Figure 3E legend
datasets from the mouse visual cortex
- p. 8 Results
3,482 cells from the prefrontal cortex
- p. 29 Methods, Transferring cell type labels onto scATAC-seq
for the mouse prefrontal cortex and scRNA-seq cells from the mouse visual cortex
Judge's note: Page 29 reads 'scATAC-seq cells ... for the mouse prefrontal cortex and scRNA-seq cells from the mouse visual cortex'. The legend's plural 'datasets' attributes both datasets to visual cortex. This is a wording misattribution in the legend; the Methods are correct.
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Wording The Figure 5D legend says 'Predicted expression patterns for four genes not originally profiled by STARmap' (and the text says 'four representative cases (Figure 5D)'), but panel D shows five predicted tiles: Tesc, Pvrl3, Sox10, Grm2, Tcrb.
- p. 48 Figure 5D legend
Predicted expression patterns for four genes not originally profiled by STARmap
- p. 12 Results
We identified four representative cases (Figure 5D)
- p. 48 Figure 5D panel
Tesc, Pvrl3, Sox10, Grm2, Tcrb
Only the authors can say what is right here.
Judge's note: Panel D on p48 shows five genes under 'Predicted'. Sox10 also appears in panel C (osmFISH), possibly as a comparison, but neither the legend nor the text explains the fifth tile. Only the authors can say which four are meant.
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Wording The Methods state "For all neuronal, bipolar, and pancreatic analyses we choose a dimensionality of 30" and list exceptions for scATAC-seq, bone marrow and the cell atlases. The mouse cortex Drop-seq STARmap analysis uses "a dimensionality of 50" and is not listed as an exception.
- p. 16 Parameters for Seurat v3 integration
For all neuronal, bipolar, and pancreatic analyses we choose a dimensionality of 30.
- p. 32 STARmap imputation with Drop-seq data
choosing a dimensionality of 50
Judge's note: Both statements are on the page images (p16, p32). This may be a preprocessing setting rather than the integration dimensionality, but the paper does not say so. It is a minor gap in the general parameter statement.
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Wording Garbled wording: "anchors representing reference and cell pairs have significantly higher scores than incorrect anchors (Figure 2I)". The contrast and Figure 2I suggest 'correct cell pairs' (same cell type) was meant.
- p. 20 Anchor scoring
anchors representing reference and cell pairs have significantly higher scores than incorrect anchors
- p. 20 Anchor scoring
anchors representing reference and cell pairs have significantly higher scores
Judge's note: The page 20 image confirms the phrase. Figure 2I and its legend compare 'Correct' (same cell type) with 'Incorrect' anchors, so the phrase misdescribes the comparison. This is a wording issue only.
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Wording Methods subdivide cells 'into CD69-high and CD69-low cells by fitting a three-component mixture model', then group them into two populations; the paper does not say how the three components map onto the two groups.
- p. 25 Analysis of CD69+ bone marrow population
fitting a three-component mixture model
- p. 25
by fitting a three-component mixture model
Only the authors can say what is right here.
Judge's note: I read p.25 (main text lines 1184-1189). The text says a three-component normalmixEM fit was used and the cells were then grouped into high and low expressers. The handling of the third component is not stated anywhere, so only the authors can resolve this.
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Typo Abstract: "imputation of spatial gene expression patterns.Our work presents" has no space after the full stop.
- p. 1 Abstract, final sentences
spatial gene expression patterns.Our work presents
- p. 1 Abstract
spatial gene expression patterns.Our work
Judge's note: The page 1 image shows the words run together with no space after 'patterns.', so this is not an extraction artefact.
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Typo The same paper is cited as "[Moffit et al., 2018]" on p13 and "[Moffitt et al., 2018]" on p3. The reference list has two entries for it: "Moffit JR, … Science 5324." and "Moffitt JR, … Science. URL 10.1126/science.aau5324".
- p. 13 Results
[Moffit et al., 2018]
- p. 36 Reference list
Moffit JR, Bambah-Mukku D
- p. 36 Reference list
Moffit JR, Bambah-Mukku D, Eichhorn SW
- p. 3 Introduction
[Moffitt et al., 2018]
Judge's note: On page 36 there are two consecutive entries with the same authors, title and year, one with the misspelled 'Moffit' and the incomplete 'Science 5324'. Page 13 shows the in-text 'Moffit'.
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Typo In the text, the mouse gene is written "MGE-derived populations (LHX6)" in human-style capitals, while the neighbouring genes (Gad2, Pvalb) and the Figure 3F label and legend use 'Lhx6'.
- p. 8 Results
MGE-derived populations (LHX6)
- p. 45 Figure 3F legend
Lhx6 600
- p. 45 Figure 3 legend (F)
Gad2, Pvalb, Sst, Vip, Lamp5, and Id2 1,000; Lhx6 600
- p. 44 Figure 3F
Neurod6 Gad2 Lhx6 Vip Lamp5 Sst Pvalb
Judge's note: The page 8 image shows italic 'LHX6' next to 'Gad2', and the figure and legend use 'Lhx6'. This is a cosmetic inconsistency. Reviewer note 3's point about the Id2 track is handled under C004.
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Typo Misspelling: "fill in missing modalites in key datasets" should read 'modalities'.
- p. 10 Transferring continuous and multimodal data
fill in missing modalites in key datasets
Judge's note: The page 10 image shows 'modalites'.
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Typo Reference 'R Testi JHP, Lanier LL, 1989 T cell activation via Leu-23 (CD69)' has garbled author names, so the in-text citation reads '[R Testi and Lanier, 1989]' (p11, p37).
- p. 37 Reference list
R Testi JHP, Lanier LL, 1989
- p. 11 Results
[R Testi and Lanier, 1989]
Judge's note: Rests on outside knowledge for the exact correct form (Testi R, Phillips JH, Lanier LL). That the printed author field 'R Testi JHP' is malformed can be seen in the image, and it produces the irregular in-text citation on p11.
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Typo Duplicated word: "genes that were not originally profiled profiled by STARmap".
- p. 12 Results, spatial mapping
not originally profiled profiled by STARmap
- p. 12 Results, spatial mapping
were not originally profiled profiled by STARmap
- p. 20 Methods
anchors representing reference and cell pairs
- p. 12
enes that were not originally profiled profiled by STARmap. We iden
Judge's note: The page 12 image shows 'profiled profiled'. Reviewer note 3's point about 'reference and cell pairs' is handled under C015.
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Typo 'both' introduces a list of three items: "including both transcriptional, posttranscriptional, and translational regulation".
- p. 15 Discussion, final paragraph
including both transcriptional, posttranscriptional, and translational regulation
Judge's note: The page 15 image confirms the wording. This is cosmetic.
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Typo Duplicated word: "One parameter we expect to fluctuate across across datasets".
- p. 16 Parameters for Seurat v3 integration
fluctuate across across datasets
- p. 16
One parameter we expect to fluctuate across across datasets
- p. 16
ameter we expect to fluctuate across across datasets represents
Judge's note: The page 16 image shows 'across across'.
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Typo Copy-editing errors in Methods: 'principle component analysis' (p.18 and p.27), 'Cusanovich and Hill et at.' (p.29), 'We then computed to log of this TF-IDF matrix' (p.29), 'by it’s contribution' (p.24).
- p. 29 Latent semantic indexing
Cusanovich and Hill et at.
- p. 29 Latent semantic indexing
We then computed to log of this TF-IDF matrix
- p. 24 CITE-seq cross-validation
by it’s contribution
- p. 27 mnnCorrect
we performed principle component analysis
Judge's note: I verified each phrase on the page images. All are cosmetic: principal, et al., the log, its.
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Typo "The canonical correlation vectors can then be obtained as the left and right singular values from the SVD" should say singular vectors.
- p. 19 CCA methods
obtained as the left and right singular values from the SVD
Judge's note: On page 19, Λ is defined as the diagonal of singular values (λ^1/2), and u_i = γ_i, v_i = δ_i are columns of the singular-vector matrices Γ and Δ. The word 'values' is a slip. The equations themselves are correct, so the result stands.
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Typo The weight-normalisation sum on p.21 is typeset with '1' as the lower limit and 'j = k.weight' as the upper limit, i.e. Σ_1^{j = k.weight} D̃_c,j, instead of the conventional Σ_{j=1}^{k.weight}.
- p. 21 Anchor weighting equation for W_c,i
Wc, i =
Judge's note: I viewed the crop. The denominator shows Σ with subscript 1 and superscript 'j = k.weight'. The intended meaning (sum over j from 1 to k.weight) can still be recovered, so this is a cosmetic notation error.
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Typo Copy-editing errors in Methods: 'accurately reflected the the mixing' (p.28), 're-compute an principal component analysis' (p.28), 'performed differential expressed to identify' (p.32).
- p. 28 Mixing metric
accurately reflected the the mixing
- p. 24 CITE-seq cross-validation
by it’s contribution
- p. 28 Mixing metric
reflected the the mixing
- p. 29 LSI
We then computed to log of this TF-IDF matrix
Judge's note: I verified each phrase on the page images. The other items in this cluster ('it’s contribution', 'computed to log', 'et at.') are handled under C027.
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Typo The supplier name is misspelled in 'RLT lysis buffer (Giagen, cat #: 79216)' on p.25.
- p. 25 Validation of CD69+ T cell population
(Giagen, cat #: 79216)
- p. 25
RLT lysis buffer (Giagen, cat #: 79216)
Only the authors can say what is right here.
Judge's note: Rests on outside knowledge: the supplier of RLT buffer is Qiagen. The page image shows 'Giagen'.
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Typo The product name is capitalised 'AmPure bead cleanup' on p.25.
- p. 25 Validation of CD69+ T cell population
AmPure bead cleanup
Only the authors can say what is right here.
Judge's note: Rests on outside knowledge: the product is branded 'AMPure'. The page image shows 'AmPure'. This is cosmetic.
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Typo The Tabula Muris methods (p.26) cite '(FindAnchors and IntegrateData)', whereas every other integration analysis names FindIntegrationAnchors.
- p. 26 Identification of rare subtypes in the Tabula Muris dataset
(FindAnchors and IntegrateData)
- p. 25 Protein expression transfer to the HCA
FindIntegrationAnchors and IntegrateData functions
Judge's note: I viewed the crop. FindAnchors appears only here (grep). Everywhere else, including the anchor-identification and HCA sections, the function is FindIntegrationAnchors.
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Typo Scrublet is cited as "Wolock et al., 2018" in the Key Resources Table but as "Wolock et al., 2019" in the Methods (pp. 25 and later) and in the reference list ("Wolock SL, Lopez R, Klein AM, 4 2019").
- p. 52 Key resources table
Wolock et al., 2018
- p. 25 Methods
Scrublet [Wolock et al., 2019]
- p. 40 References
Wolock SL, Lopez R, Klein AM, 4 2019
Judge's note: I checked the page 52 table ("Wolock et al., 2018"), the page 25 Methods text ("Scrublet [Wolock et al., 2019]"), and the page 40 reference list, which has only one Wolock entry, dated 2019. A search of the text found a second in-text citation, also 2019 (line ~1452). The reference list has no 2018 Wolock entry, so the table's year does not match any reference. This is a minor inconsistency in a citation year.
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Typo The section heading on p.30 is misspelled 'Psuedo-bulk ATAC-seq data collation', while the body text spells it 'pseudo-bulk'.
- p. 30 Methods heading
Psuedo-bulk ATAC-seq data collation
Judge's note: The page image shows the heading 'Psuedo-bulk'; the same paragraph uses 'pseudo-bulk'.
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Typo Methods, Analysis of integrated STARmap data (p32): 'We then performed differential expressed to identify gene expression markers' should read 'differential expression'.
- p. 32 Analysis of integrated STARmap data
We then performed differential expressed to identify
- p. 32
We then performed differential expressed to identify gene expression markers
Judge's note: The page image shows the wrong word form exactly as quoted.
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Typo Reference Hie et al. 2018 (p35): 'data. bioRvix.' misspells bioRxiv.
- p. 35 Reference list, Hie et al.
data. bioRvix.
Judge's note: The image shows 'bioRvix' as printed. Elsewhere the reference list spells it 'biorxiv' (www.biorxiv.org).
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Typo Reference list typos: Halpern et al. 2017 prints 'Shenhav1 R' with a stray digit (p35), and the van Dijk et al. 2018 DOI is printed 'doi.org/10.10167j.cell.2018.05.061', with '7' in place of '/' (p39).
- p. 35 Reference list
Shenhav1 R
- p. 35 Reference list, Halpern et al., 2017
Halpern KB, Shenhav1 R
- p. 39 van Dijk reference
doi.org/10.10167j.cell.2018.05.061
Judge's note: Both are visible in the page images at normal type size, not as superscripts, so they are printed and are not extraction artefacts. The other Cell DOIs in the list use the form 10.1016/j.cell.
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Typo Saunders et al. 2018 author list repeats names: 'Saunders A, Macosko EZ, Wysoker A, Brumbaugh S, Kulp D, Mccarroll SA, Saunders A, Macosko EZ, Wysoker A, Goldman M, Krienen FM' (p37).
- p. 37 Reference list
Mccarroll SA, Saunders A, Macosko EZ, Wysoker A
Judge's note: The image confirms that Saunders A, Macosko EZ and Wysoker A each appear twice.
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Typo The Figure 2K y-axis label reads 'Silhoutte Metric' (misspelling of Silhouette).
- p. 43 Figure 2K y-axis
Silhoutte Metric
Judge's note: Seen on the full-page image p43, panel K.
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Typo The Figure 3F legend has a garbled phrase: 'by pooling together cells with for each cell type'.
- p. 45 Figure 3F legend
by pooling together cells with for each cell type
- p. 45 Figure 3 legend (F)
pooling together cells with for each cell type
Judge's note: Printed on p45 as quoted. A word is missing or 'with' is left over from an edit.
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Typo The Figure 4E legend reads 'a similar set of deferentially expressed genes'; it should be 'differentially'.
- p. 47 Figure 4E legend
similar set of deferentially expressed genes
- p. 47 Figure 4 legend (E)
deferentially expressed genes
- p. 45 Figure 3 legend (F)
pooling together cells with for each cell type
Judge's note: Printed on p47 as quoted. The Fig. 3F phrase also mentioned by one reviewer is covered by C039.
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Typo The Figure 5C legend describes osmFISH as 'a highly sensitive single molecular assay'; the Results (p12) say 'cyclic single molecule FISH'.
- p. 48 Figure 5 legend (C)
a highly sensitive single molecular assay
Judge's note: The legend on p48 reads as quoted. 'single-molecule' is the usual term, and 'single molecular assay' can be misread as 'one assay'. This is a minor wording inconsistency.
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