heimannch
commented
1 year ago Hello @jbannon, thanks for using iAtlas and for bringing this to our attention!
We have a page in our portal that describes the methods to generate the variables used in the portal.
However, I see that there is an error in the path to get the methods of the features you described. We'll update it accordingly and, for your easy reference, I list the references here too:
IMPRES: IMPRES scores were calculated as described(Auslander, et al., 2018) and implemented in the Vincent Lab R-package, binfotron::calc_impres (devtools::install_github(“Benjamin-Vincent-Lab/binfotron”).
MIRACLE: MIRACLE scores were calculated as described (Turan, et al., 2021)
ICP Ratios: Biocarta or Reactome CTLA4 signature normalized by the Bindea signature (eg CTLA vs Th1: BIOCARTA_CTLA4_PATHWAY signature score / Bindea_Th1_Cells signature score)
Gene signature derivation: Gene signatures were derived by running DESeq2(Love, et al., 2014) on gene count data and grouping the significant up and down genes in their respective signatures.
Gene signature calculations: Gene counts were upper-quartile normalized and then log2 transformed, log2(normalized counts +1). Signatures were calculated as the median log2-transformed value of the genes in a given gene signature.
Gene signature sources:
Beck_Mac_CSF1(Beck, et al., 2009)
Bindea_BCells, Bindea_aDC, Bindea_DC, Bindea_Eosinophils, Bindea_iDC, Bindea_Mast_Cells, Bindea_Neutrophils, Bindea_NK_CD56bright, Bindea_NK_CD56dim, Bindea_NK_Cells, Bindea_pDC, Bindea_Tcm, Bindea_Tem, Bindea_TFH, Bindea_Tgd, Bindea_CD8_TCells, Bindea_TCells, Bindea_THelper, Bindea_Th1_Cells, Bindea_Th2_Cells, Bindea_Th17_Cells, Bindea_TReg, Bindea_Cytotoxic_Cells, Bindea_Macrophages(Bindea, et al., 2013)
BIOCARTA_CTLA4_PATHWAY(Nishimura, 2004)
Chan_TIC(Chan, et al., 2009)
Chang_Serum_Response_Up, CSF1_Response, LIexpression_Score, Module3_IFN_Score, TGFB_Score(Thorsson, et al., 2018)
Cytolytic_Score(Roufas, et al., 2018)
Fan_IGG(Fan, et al., 2011)
GO_BCR_Signaling(Gene Ontology terms 0050853 - GO:0050853)
GO_TCR_Signaling(Gene Ontology terms 0050852 - GO:0050852)
IglesiaVincent_BCell, IglesiaVincent_CD8, IglesiaVincent_CD68, IglesiaVincent_MacTh1, IglesiaVincent_TCell (Iglesia, et al., 2014)
KardosChai_ImSuppress, KardosChai_EMT_DOWN, KardosChai_EMT_UP (Kardos, et al., 2016)
Palmer_BCell, Palmer_CD8, Palmer_TCell(Palmer, et al., 2006)
Prat_Claudin(Prat, et al., 2010)
REACTOME_CTLA4_INHIBITORY_SIGNALING, REACTOME_PD1_SIGNALING (Subramanian, et al., 2005)
Rody_IL8, Rody_LCK, Rody_TNBC_BCell, Rody_TNBC_TCell (Rody, et al., 2009)
Schmidt_BCell(Schmidt, et al., 2008)
IPRES Signatures(Hugo, et al., 2016)
Vincent_IPRES_NonResponder - Vincent Lab analysis of Hugo data; genes up in non-responders
References
Auslander, N., et al. Robust prediction of response to immune checkpoint blockade therapy in metastatic melanoma. Nat Med 2018;24(10):1545-1549.
Balar, A.V., et al. Atezolizumab as first-line treatment in cisplatin-ineligible patients with locally advanced and metastatic urothelial carcinoma: a single-arm, multicentre, phase 2 trial. Lancet 2017;389(10064):67-76.
Beck, A.H., et al. The macrophage colony-stimulating factor 1 response signature in breast carcinoma. Clin Cancer Res 2009;15(3):778-787.
Bindea, G., et al. Spatiotemporal dynamics of intratumoral immune cells reveal the immune landscape in human cancer. Immunity 2013;39(4):782-795.
Bolotin, D.A., et al. MiXCR: software for comprehensive adaptive immunity profiling. Nat Methods2015;12(5):380-381.
Chan, K.S., et al. Identification, molecular characterization, clinical prognosis, and therapeutic targeting of human bladder tumor-initiating cells. Proc Natl Acad Sci U S A 2009;106(33):14016-14021.
Chiu, C.H., et al. An improved nonparametric lower bound of species richness via a modified good-turing frequency formula. Biometrics 2014;70(3):671-682.
Cloughesy, T.F., et al. Neoadjuvant anti-PD-1 immunotherapy promotes a survival benefit with intratumoral and systemic immune responses in recurrent glioblastoma. Nat Med 2019;25(3):477-486.
Dobin, A., et al. STAR: ultrafast universal RNA-seq aligner. Bioinformatics 2013;29(1):15-21.
Durinck, S., et al. Mapping identifiers for the integration of genomic datasets with the R/Bioconductor package biomaRt. Nat Protoc 2009;4(8):1184-1191.
Fan, C., et al. Building prognostic models for breast cancer patients using clinical variables and hundreds of gene expression signatures. BMC Med Genomics 2011;4:3.
Gide, T.N., et al. Distinct Immune Cell Populations Define Response to Anti-PD-1 Monotherapy and Anti-PD-1/Anti-CTLA-4 Combined Therapy. Cancer Cell 2019;35(2):238-255 e236.
Hugo, W., et al. Genomic and Transcriptomic Features of Response to Anti-PD-1 Therapy in Metastatic Melanoma. Cell 2016;165(1):35-44. Iglesia, M.D., et al. Prognostic B-cell signatures using mRNA-seq in patients with subtype-specific breast and ovarian cancer. Clin Cancer Res 2014;20(14):3818-3829.
Kardos, J., et al. Claudin-low bladder tumors are immune infiltrated and actively immune suppressed. JCI Insight 2016;1(3):e85902.
Lefranc, M.P. IMGT, the International ImMunoGeneTics Information System. Cold Spring Harb Protoc2011;2011(6):595-603.
Love, M.I., Huber, W. and Anders, S. Moderated estimation of fold change and dispersion for RNA-seq data with DESeq2. Genome Biol 2014;15(12):550.
Newman, A.M., et al. Determining cell type abundance and expression from bulk tissues with digital cytometry. Nat Biotechnol 2019;37(7):773-782.
Nishimura, D. A View From the Web: BioCarta. Biotechnology Software & Internet Journal 2004;2(3):117-120.
Palmer, C., et al. Cell-type specific gene expression profiles of leukocytes in human peripheral blood. BMC Genomics 2006;7:115.
Patro, R., et al. Salmon provides fast and bias-aware quantification of transcript expression. Nat Methods2017;14(4):417-419.
Pielou, E.C. Species-diversity and pattern-diversity in the study of ecological succession. J Theor Biol1966;10(2):370-383.
Prat, A., et al. Phenotypic and molecular characterization of the claudin-low intrinsic subtype of breast cancer. Breast Cancer Res 2010;12(5):R68.
R Core Team. 2014. R: A language and environment for statistical computing. http://www.r-project.org/
Riaz, N., et al. Tumor and Microenvironment Evolution during Immunotherapy with Nivolumab. Cell2017;171(4):934-949 e916.
Rody, A., et al. T-cell metagene predicts a favorable prognosis in estrogen receptor-negative and HER2-positive breast cancers. Breast Cancer Res 2009;11(2):R15.
Rosenberg, J.E., et al. Atezolizumab in patients with locally advanced and metastatic urothelial carcinoma who have progressed following treatment with platinum-based chemotherapy: a single-arm, multicentre, phase 2 trial. Lancet 2016;387(10031):1909-1920.
Roufas, C., et al. The Expression and Prognostic Impact of Immune Cytolytic Activity-Related Markers in Human Malignancies: A Comprehensive Meta-analysis. Front Oncol 2018;8:27.
Schmidt, M., et al. The humoral immune system has a key prognostic impact in node-negative breast cancer. Cancer Res 2008;68(13):5405-5413.
Shannon, C.E. A Mathematical Theory of Communication. The Bell System Technical Journal 1948;27:379–423, 623–656.
Shugay, M., et al. VDJtools: Unifying Post-analysis of T Cell Receptor Repertoires. PLoS Comput Biol2015;11(11):e1004503.
Subramanian, A., et al. Gene set enrichment analysis: a knowledge-based approach for interpreting genome-wide expression profiles. Proc Natl Acad Sci U S A 2005;102(43):15545-15550.
Turan T., et al. A balance score between immune stimulatory and suppressive microenvironments identifies mediators of tumour immunity and predicts pan-cancer survival. Br J Cancer. 2021 Feb;124(4):760-769.
Van Allen, E.M., et al. Genomic correlates of response to CTLA-4 blockade in metastatic melanoma. Science2015;350(6257):207-211.
When downloading this file ('iatlas-ici-features.tsv') from the Synapse portal it's not given in the description what the meaning of the columns are.
There seem to be columns linked to various studies ('BIOCARTA_CTLA4_V_Palmer_CD8') across multiple resources ('REACTOME_CTLA4_V_Palmer_CD8') and then ones without any obvious biological interpretation ('Miracle').
Adding a description of the content of this file would be extremely useful.
Cheers, James