A pan-cancer splicing-based immune evasion score (SIES)
Solo researcher from a Bangladeshi university, MS in Applied Statistics. No PI, no lab, no funding. Built a pan-cancer splicing-based immune evasion score (SIES) over the last several months and now trying to find the right home for it. Four desk rejections in three weeks and I want to figure out if it's a journal-fit problem or a framing problem before submitting again.
The work in brief:
Pre-specified 35-gene immune-pathway panel (no outcome-based selection)
PSI-level PCA on 5,372 TCGA patients across 19 cancer types
SIES predicts anti-PD-L1 non-response in IMvigor210 (N=192): AUC 0.690 [0.587-0.791]
Statistically orthogonal to TMB (Spearman rs=-0.022, p=0.793)
Combined SIES+TMB cross-validated AUC=0.790
Benchmarked against 6 established biomarkers (IFN-γ 6-gene, T-cell GEP 18-gene, CD8A, cytolytic activity, PD-L1, MHC-I): SIES falls in the middle of the pack on raw discrimination but is the only one orthogonal to TMB
1,000-iteration random gene-set null test: zero of 1,000 random 42-gene panels reached observed AUC (empirical p=0.001)
Residual-SIES after orthogonalisation against both IFN-γ and T-cell GEP retains AUC=0.689
Stratified Cox HR=1.11 per SD, p=2.84×10⁻⁴ across 9 cancer types (n=3,012)
All code and intermediate result tables on GitHub
Acknowledged weaknesses (already in the paper):
IMvigor210 validation uses an expression surrogate, not actual splicing data (splice-resolved RNA-seq not publicly available for this cohort)
Riaz 2017 secondary cohort gave AUC 0.641 [0.423-0.845], CI crosses 0.5, owned transparently
C-index 0.539 is modest, framed as population-level mechanistic stratification not individual prognostic
PCA PC1 explains 6.2% of post-normalisation variance
Rejection history:
Nature Communications: desk reject, "of interest to a more specialised journal"
Genome Medicine: desk reject, "doesn't meet broad-interest threshold"
JITC: explored, pre-screen feedback suggested in-silico work without wet-lab validation is poor fit
Briefings in Bioinformatics: submitted as Case Study (their guidelines say no original research), desk reject in 24 hours, generic form letter, OUP transfer offered
My read of the pattern:
Clinical-translational journals (NC, GM, JITC) seem to downweight pure in-silico work. Bioinformatics-methods journals (BIB) may read the paper as too biology-claim-heavy and not methods-novel-enough. The paper sits in a hybrid space, phenomenon + new specificity-control methodology + clinical-cohort validation, and doesn't fit cleanly into any standard slot.
Questions for the community:
Is the pattern I'm reading correct, or am I missing something more fundamental?
For papers in this hybrid space (pre-specified pathway score + ICI cohort validation + specificity controls but no wet-lab), where do they actually land? Specific journal recommendations from people who've published similar work would help enormously.
NAR Genomics and Bioinformatics, PLOS Computational Biology, NAR Cancer, Bioinformatics, Briefings in Functional Genomics, npj Precision Oncology, Cancer Research Communications, which of these (if any) would you target, and which would you avoid?
Is there a framing reformulation I'm missing? "Method paper with biological application" versus "Biology paper with methodological controls" does the same content read differently depending on which way it's framed?
Is four desk rejections in three weeks an unusual pattern, or is this just normal noise for hybrid papers? Trying to calibrate whether I'm reading too much into it.
Not looking for sympathy or "keep going" reassurance. Looking for editorial-judgment feedback from people who have published in this space, ideally including people who have themselves received and recovered from desk rejections.
Happy to share the preprint or specific sections if it helps the read.
Thanks in advance. Please don't take offense with me declaring I don't want sympathy or keep going cheers, just frustrated.