Table 3.

Potential clinicopathological scenarios where biopsy-based transcriptomics might help with diagnosis

Banff Classification Category	Banff Classification sub-category	Histological challenge	How would biopsy-based transcriptomics help?	References
Normal biopsy or nonspecific changes		Banff lesion scores below threshold for rejection (TCMR or AMR)	Is there molecular TCMR? Is there molecular AMR? How severe is the injury-repair response?	[15,24▪▪,26▪▪]
		DSA-positive, negative histology	Is there molecular AMR?	[22▪▪,24▪▪,53]
		Acute tubular injury	How severe is the injury-repair response?	[45▪]
Antibody-mediated rejection	Active AMR	Probable AMR (DSA+ with g1, ptc1, v or TMA)	Is there molecular AMR?	[24▪▪]
		MVI+ DSA- C4d-	Is there molecular AMR? Can molecular findings distinguish causes of MVI (e.g. HLA antibody, non-HLA antibody, missing self, etc)?	[17,24▪▪,50]
	Chronic/chronic active AMR		Degree of injury-repair response? Degree of chronicity?	[45▪,61]
	C4d staining without evidence of rejection		Is there molecular AMR?	[13]
Borderline for TCMR			Is there molecular TCMR? Is there molecular AMR?	[15,31,62]
TCMR	TCMR grade II and III	Presence of endarteritis	Is there molecular TCMR? Is there molecular AMR?	[52]
	Chronic-active TCMR	i-IFTA lesion	Is there molecular TCMR? Is there molecular AMR? How severe is the injury-repair response?	[54]
Mixed AMR and TCMR			Is there molecular TCMR? Is there molecular AMR?
IFTA NOS		Scarring? cause	Is there molecular TCMR? Is there molecular AMR? How severe is the injury-repair response?	[54]
Other findings	Polyomavirus nephropathy		Molecular identification of BK virus Is there molecular TCMR?	[56,57]
	Glomerulonephritis		Is there molecular AMR?

AMR, antibody-mediated rejection; DSA, donor specific antibody; g, glomerulitis; MVI, microvascular inflammation; ptc, peritubular capillaritis; TCMR, T-cell mediated rejection; TMA, thrombotic microangiopathy; v, intimal arteritis.