"""Per-protein manual decisions for the 283 vesicle-type dossiers (vesicle_review/dossiers.yaml). Written by a reviewer after reading each gene's dossier rows (UniProt location/function and features, other location annotations as leads, source sample, current review). Nothing here is computed. Decisions are per protein because every row of a gene asserts the same thing (a vesicle-type location from an EV proteome); where the sample type would change the call it is said in the basis, and R holds per-row overrides where a protein's rows differ in sample (ALB). APOE's one row here is a plasma-microvesicle sample; its other vesicle rows, from non-plasma samples, were reviewed in decisions_settled.py and kept. Framework: MISEV2018 (PMID:30637094), section 4-b-1 and Table 3, used as a guide for each judgement, not as a rule: * Category 1 (transmembrane/GPI proteins of the plasma membrane or endosomes) and Category 2 (cytosolic proteins, including promiscuous cargo such as cytosolic enzymes and cytoskeleton) are expected EV contents. The location is true but is not where the protein works -> KEEP_AS_NON_CORE. * Category 3 (major constituents of co-isolated non-EV structures; APOA1/2, APOB and ALB are the recommended negative markers for plasma/serum EVs) -> MARK_AS_OVER_ANNOTATED. * Category 4 (residents of nucleus, mitochondria, ER, Golgi, autophagosome, peroxisome: found in some EVs but not enriched in small EVs of plasma-membrane/endosome origin), for an *exosome* annotation -> MARK_AS_OVER_ANNOTATED. * Category 5 (secreted or lumenal proteins; association with EVs needs the cognate EV receptor to be explored) -> MARK_AS_OVER_ANNOTATED absent such evidence. * ACCEPT only where the protein itself works in EV biogenesis (ALIX/PDCD6IP; UniProt, PubMed:22660413). MISEV places ALIX in category 2a with TSG101 and the CHMPs, so this is a protein-specific call, not a category one. """ CAT1 = ("KEEP_AS_NON_CORE", "Transmembrane/lipid-anchored protein of the plasma membrane or endosomal system " "(UniProt); such proteins are expected EV contents (MISEV2018 (PMID:30637094) category 1). True, but not its core location.") # the same, for proteins whose plasma-membrane or endosomal location is recorded in GO rather than UniProt CAT1_GO = (CAT1[0], CAT1[1].replace("plasma membrane or endosomal system (UniProt)", "plasma membrane or endosomal system (UniProt membrane topology; compartment from GO)")) CAT2 = ("KEEP_AS_NON_CORE", "Cytosolic protein (UniProt); cytosolic proteins, including abundant enzymes and " "cytoskeletal proteins, are expected and often promiscuous EV contents (MISEV2018 (PMID:30637094) category 2b). True, but " "not its core location.") # the same, for proteins whose cytosolic location is recorded in GO rather than UniProt CAT2_GO = (CAT2[0], CAT2[1].replace("Cytosolic protein (UniProt)", "Cytosolic protein (GO cytosol or cytoplasm annotation)")) CAT2A = ("KEEP_AS_NON_CORE", "Cytosolic protein with lipid or membrane-protein binding ability; MISEV2018 (PMID:30637094) " "category 2a lists such proteins (ESCRT components, ALIX, annexins, HSPA8 and others) as expected EV contents. True, " "but not its core location.") CAT3 = ("MARK_AS_OVER_ANNOTATED", "MISEV2018 (PMID:30637094) category 3a covers non-EV structures that " "co-isolate with EVs, chiefly lipoproteins and albumin, from plasma, serum and serum-containing culture; " "detection does not establish EV localization.") CAT4 = ("MARK_AS_OVER_ANNOTATED", "Mainly resident in an intracellular compartment that MISEV2018 (PMID:30637094) lists as not " "enriched in small EVs of plasma-membrane/endosomal origin (category 4), and its own review keeps no experimental " "cell-surface or plasma-membrane pool; an exosome annotation from a bulk EV proteome is not supported.") CAT4_SURFACE = ("KEEP_AS_NON_CORE", "Mainly resident in an intracellular compartment that MISEV2018 (PMID:30637094) lists " "as not enriched in small EVs (category 4), but with an experimentally documented cell-surface or " "plasma-membrane pool that its own review keeps; small EVs budding from the plasma membrane can carry " "that pool, so the detection is plausible. True, but not its core location.") CAT5 = ("MARK_AS_OVER_ANNOTATED", "Secreted or lumenal protein (UniProt). MISEV2018 (PMID:30637094) category 5 " "allows such proteins onto EVs through specific or promiscuous (proteoglycan, lipid) receptors on the EV " "surface, but asks that their identification be backed by evidence of that association. A bulk EV proteome " "cannot separate surface binding from co-isolation, and this protein's annotations record no experimental " "proteoglycan, heparin or lipid binding, and its own review keeps no experimental cell-surface or " "plasma-membrane pool.") CAT5_SURFACE = ("KEEP_AS_NON_CORE", "Secreted or lumenal protein (UniProt) with an experimentally documented cell-surface " "or plasma-membrane pool that its own review keeps. MISEV2018 (PMID:30637094) category 5 allows such " "proteins onto EVs through specific or promiscuous receptors on the EV surface, and small EVs budding " "from the plasma membrane can carry a surface-bound pool, so the detection is plausible. True, but not " "its core location.") CAT5_BOUND = ("KEEP_AS_NON_CORE", "MISEV2018 (PMID:30637094) category 5 allows secreted proteins onto EVs through " "promiscuous (proteoglycan, lipid) receptors on the EV surface, so the detection is plausible. True, " "but not its core location.") CAT3B = ("MARK_AS_OVER_ANNOTATED", "Ribosomal protein; MISEV2018 (PMID:30637094) category 3b lists ribosomal proteins " "among the protein and protein/nucleic-acid aggregates that co-isolate with EVs, so detection does not establish EV " "localization.") def note(base: tuple[str, str], extra: str) -> tuple[str, str]: text = base[1] if "PMID:30637094" in extra: # cite the paper once per reason text = text.replace("MISEV2018 (PMID:30637094)", "MISEV2018") return (base[0], f"{extra} {text}") G = { "AARS1": note(CAT2, "Cytoplasmic aminoacyl-tRNA synthetase."), "ABCB4": note(CAT1, "Canalicular plasma-membrane phospholipid flippase."), "ACLY": note(CAT2, "Cytosolic ATP-citrate lyase."), "ACSL4": note(CAT4, "UniProt places ACSL4 in mitochondrial outer, peroxisomal and ER membranes."), "ACTA1": note(CAT2, "Actin."), "ACTB": note(CAT2, "Cytoplasmic actin."), "ACTG2": note(CAT2, "Smooth-muscle actin."), "ACTR1A": note(CAT2, "Dynactin Arp1 subunit."), "ACTR1B": note(CAT2, "Dynactin Arp1 subunit."), "ADGRV1": note(CAT1, "Plasma-membrane adhesion GPCR."), "AGT": note(CAT5, "Secreted angiotensinogen."), "AHCTF1": note(CAT4, "Nuclear pore assembly factor (nucleus, nuclear envelope)."), "AHCY": note(CAT2, "Cytoplasmic adenosylhomocysteinase."), "AK2": note(CAT4, "Mitochondrial intermembrane-space adenylate kinase."), "ALB": note(CAT3, "Serum albumin, which MISEV2018 (PMID:30637094) names as a negative marker; see R for " "each row's sample."), "ALDH7A1": note(CAT2, "Cytosolic isoform (UniProt isoform 2: cytosol)."), "ALDOB": note(CAT2, "Cytosolic aldolase."), "ALK": note(CAT1, "Plasma-membrane receptor tyrosine kinase."), "ALPL": note(CAT1, "GPI-anchored plasma-membrane alkaline phosphatase."), "ANXA11": note(CAT2A, "Calcium-dependent membrane-binding annexin; annexins are classic category 2a EV proteins."), "AP2M1": note(CAT2A, "Plasma-membrane clathrin adaptor subunit (peripheral, cytosolic face)."), "AP4M1": note(CAT4, "AP-4 coat subunit of the trans-Golgi network (UniProt ECO:0000269)."), "APAF1": note(CAT2, "Cytoplasmic apoptosome scaffold."), "APOB": note(CAT3, "Apolipoprotein B, named by MISEV2018 (PMID:30637094) as a negative marker."), "APOE": note(CAT3, "Apolipoprotein E recovered from a plasma microvesicle preparation. MISEV2018 " "(PMID:30637094) names APOA1/2 and APOB, not APOE, as negative markers, but APOE is carried " "on the same plasma lipoproteins, so this sample cannot separate the two. The earlier ACCEPT " "described APOE's lipoprotein biology, not EV localization. (APOE's other vesicle rows, " "from non-plasma samples, are KEEP_AS_NON_CORE; see decisions_settled.py.)"), "APOL1": note(CAT3, "HDL-associated apolipoprotein L1, recovered from a plasma microvesicle preparation."), "APP": note(CAT1, "Plasma-membrane/endosomal type I membrane protein; the earlier ACCEPT gave no basis for " "exosomes being a core location."), "APPL2": note(CAT2A, "Peripheral early-endosome adaptor."), "APRT": note(CAT2, "Cytosolic salvage enzyme."), "ARF1": note(CAT2A, "Myristoylated cytosolic small GTPase that cycles onto membranes."), "ARHGAP23": note(CAT2_GO, "Cytosolic Rho GAP."), "ARHGEF18": note(CAT2, "Cytoplasmic/cortical Rho GEF."), "ARL6": note(CAT2A, "Peripheral ciliary-membrane GTPase (urinary EVs carry ciliary proteins)."), "ARL8A": note(CAT2A, "Peripheral late-endosome/lysosome GTPase."), "ARL8B": note(CAT2A, "Peripheral late-endosome/lysosome GTPase."), "ARMC9": note(CAT2, "Cytoplasmic ciliary basal-body protein."), "ARPC1B": note(CAT2, "Arp2/3 complex subunit."), "ARSA": note(CAT5, "Soluble lysosomal sulfatase."), "ARSB": note(CAT5, "Soluble lysosomal sulfatase."), "ASS1": note(CAT2, "Cytosolic urea-cycle enzyme."), "ATIC": note(CAT2, "Cytosolic purine-synthesis enzyme."), "ATP1A1": note(CAT1, "Plasma-membrane Na+/K+-ATPase."), "ATP1A2": note(CAT1, "Plasma-membrane Na+/K+-ATPase."), "ATP1A3": note(CAT1, "Plasma-membrane Na+/K+-ATPase."), "ATP2B2": note(CAT1, "Plasma-membrane Ca2+-ATPase."), "ATP6AP1": note(CAT4, "UniProt places ATP6AP1 in ER and ER-Golgi intermediate compartment membranes."), "ATP6AP2": note(CAT1, "Prorenin receptor / V-ATPase accessory protein, with UniProt lysosome-membrane and cell-surface " "locations."), "ATP6V0A1": note(CAT1_GO, "V-ATPase V0 a1 subunit of endosomal/vesicle membranes."), "ATP6V1A": note(CAT2A, "V-ATPase V1 subunit, assembled on endosomal and apical membranes from the cytosol."), "ATP6V1B1": note(CAT2A, "V-ATPase V1 subunit of the apical membrane of renal intercalated cells."), "ATP6V1B2": note(CAT2A, "V-ATPase V1 subunit."), "ATP6V1C1": note(CAT2A, "V-ATPase V1 subunit."), "ATP6V1C2": note(CAT2A, "V-ATPase V1 subunit."), "ATP6V1D": note(CAT2A, "V-ATPase V1 subunit."), "ATP6V1E1": note(CAT2A, "V-ATPase V1 subunit."), "ATP6V1F": note(CAT2A, "V-ATPase V1 subunit."), "ATP6V1H": note(CAT2A, "V-ATPase V1 subunit."), "AUP1": note(CAT4, "ER-membrane and lipid-droplet protein (UniProt ECO:0000269)."), "BLVRB": note(CAT2, "Cytoplasmic reductase."), "BPGM": note(CAT2_GO, "Cytosolic erythrocyte enzyme."), "BPTF": note(CAT4, "Nuclear chromatin-remodelling subunit."), "BTD": note(CAT5, "Secreted biotinidase."), "C1GALT1C1": note(CAT4, "ER-membrane chaperone (Cosmc)."), "C1QB": note(CAT5_BOUND, "Secreted complement C1q subunit with experimental phosphatidylserine binding (IDA)."), "C3": note(CAT5_SURFACE, "Secreted complement C3; C3b binds covalently to cell surfaces through its exposed " "thioester, and its review accepts five cell-surface rows by EXP."), "CACNA2D1": note(CAT1, "Plasma-membrane calcium-channel subunit."), "CACYBP": note(CAT2, "Cytoplasmic/nuclear calcyclin-binding protein."), "CAD": note(CAT2, "Cytoplasmic pyrimidine-synthesis enzyme."), "CAND1": note(CAT2, "Cytoplasmic cullin-exchange factor."), "CANT1": note(CAT4, "ER/Golgi-membrane nucleotidase."), "CANX": note(CAT4, "ER-membrane chaperone; calnexin is a commonly used ER (non-small-EV) marker."), "CAPN5": note(CAT2_GO, "Cytosolic calpain."), "CARD11": note(CAT2, "Cytoplasmic/membrane-raft signalling scaffold."), "CC2D1A": note(CAT2, "Cytoplasmic protein that binds ESCRT-III."), "CD2AP": note(CAT2, "Cytoplasmic adaptor linking membrane proteins to actin."), "CHMP3": note(CAT2A, "ESCRT-III subunit acting on the cytosolic face of endosomes; its presence in EVs follows from " "ILV formation, but the exosome is a destination, not where it acts."), "CLU": note(CAT5_SURFACE, "Secreted clusterin (UniProt isoform 1: secreted), with receptor-mediated cell-surface " "and plasma-membrane pools by IDA (PMID:17567961, PMID:30333625). The earlier ACCEPT " "rested on its being secreted, which does not make the exosome its core location. " "Applies to the plasma microvesicle row too."), "CR1": note(CAT1_GO, "Plasma-membrane complement receptor (podocyte/erythrocyte)."), "CRYAB": note(CAT2, "Cytoplasmic small heat-shock protein."), "CSNK2B": note(CAT2_GO, "CK2 regulatory subunit (cytoplasmic and nuclear)."), "CTH": note(CAT2, "Cytoplasmic enzyme."), "CTNNB1": note(CAT2, "Cytoplasmic/junctional beta-catenin."), "CUL3": note(CAT2, "Cullin scaffold with a cytoplasmic pool."), "DDB1": note(CAT2, "Cytoplasmic/nuclear CRL4 adaptor."), "DNAJC7": note(CAT2, "Cytoplasmic co-chaperone."), "DUT": note(CAT4, "Nuclear and mitochondrial dUTPase isoforms (UniProt)."), "DYNC1H1": note(CAT2, "Cytoplasmic dynein heavy chain."), "ENO3": note(CAT2, "Cytoplasmic enolase."), "ENPP4": note(CAT1, "Plasma-membrane ectoenzyme; the earlier ACCEPT asserted activity in exosomes without evidence."), "FASN": note(CAT2, "Cytoplasmic fatty-acid synthase."), "FTCD": note(CAT2, "Cytosolic enzyme."), "GAA": note(CAT5, "Soluble lysosomal alpha-glucosidase."), "GAPDH": note(CAT2, "Cytosolic glycolytic enzyme found in many EV proteomes; the exosome is a destination, not " "GAPDH's core location, so the earlier ACCEPT is downgraded."), "GART": note(CAT2_GO, "Cytosolic purine-synthesis enzyme."), "GATM": note(CAT4, "Mitochondrial intermembrane-space enzyme."), "GBE1": note(CAT2_GO, "Cytosolic glycogen-branching enzyme."), "GGCT": note(CAT2_GO, "Cytosolic enzyme."), "GLUL": note(CAT2, "Cytosolic glutamine synthetase."), "GPC4": note(CAT1, "GPI-anchored plasma-membrane glypican."), "GPD1": note(CAT2, "Cytoplasmic enzyme."), "GPX4": note(CAT2, "Cytoplasmic isoform of the peroxidase."), "GRHPR": note(CAT2_GO, "Cytosolic reductase."), "GRID1": ("MARK_AS_OVER_ANNOTATED", "Postsynaptic glutamate-receptor delta subunit whose expression is essentially " "restricted to the CNS; detection in urinary exosomes is implausible for the " "native protein and more likely a peptide misassignment."), "HBS1L": note(CAT2, "Cytoplasmic GTPase."), "HEXB": note(CAT5, "Soluble lysosomal hexosaminidase."), "HSPA1A": note(CAT2, "Cytosolic Hsp70; Hsp70 is a classic category 2 EV protein. Expected EV cargo, not a core " "location, so the earlier ACCEPT is downgraded. Applies to the plasma microvesicle row too."), "IMPDH2": note(CAT2, "Cytosolic enzyme."), "LDHA": note(CAT2, "Cytoplasmic lactate dehydrogenase."), "LDHB": note(CAT2, "Cytoplasmic lactate dehydrogenase."), "LMAN1": note(CAT4, "ERGIC/Golgi membrane lectin."), "LMAN2": note(CAT4_SURFACE, "ERGIC/Golgi membrane lectin; cell-surface and plasma-membrane pool by IDA (PMID:22016386)."), "MDH1": note(CAT2, "Cytosolic malate dehydrogenase."), "MDH2": note(CAT4, "Mitochondrial matrix malate dehydrogenase."), "MGAT1": note(CAT4, "Golgi-membrane glycosyltransferase."), "MYH10": note(CAT2_GO, "Non-muscle myosin II."), "MYH9": note(CAT2, "Non-muscle myosin II."), "NAGK": note(CAT2_GO, "Cytosolic kinase."), "NANS": note(CAT2_GO, "Cytosolic sialic-acid synthase."), "NEU1": note(CAT5_SURFACE, "Lysosomal sialidase (lysosome lumen/membrane), with a plasma-membrane pool by IDA " "(PMID:27917893)."), "NRAS": note(CAT1, "Lipid-anchored plasma-membrane GTPase (cytoplasmic face)."), "PAICS": note(CAT2_GO, "Cytosolic purine-synthesis enzyme."), "PARK7": note(CAT2, "Cytoplasmic DJ-1; its EV presence matters as a biomarker, not as its site of action, so the " "earlier ACCEPT is downgraded."), "PDCD6IP": ("ACCEPT", "ALIX itself works in EV biogenesis: UniProt records that it sorts multivesicular-body cargo into " "intralumenal vesicles and regulates exosome biogenesis with SDC1/4 and SDCBP (PubMed:22660413). This is a " "protein-specific call, not a MISEV category one: MISEV2018 (PMID:30637094) lists ALIX in category 2a " "together with TSG101 and the CHMPs."), "PDXK": note(CAT2, "Cytosolic kinase."), "PEX1": note(CAT2, "Cytosolic AAA ATPase recruited to peroxisomes (UniProt cytosol, ECO:0000269)."), "PFAS": note(CAT2, "Cytoplasmic purine-synthesis enzyme."), "PGAM2": note(CAT2_GO, "Cytosolic glycolytic enzyme."), "PGD": note(CAT2, "Cytoplasmic pentose-phosphate enzyme."), "PGLS": note(CAT2, "Cytoplasmic pentose-phosphate enzyme."), "PLCG2": note(CAT2A, "Cytoplasmic/membrane-raft phospholipase."), "PMVK": note(CAT2, "Cytosolic kinase."), "PPP2R1A": note(CAT2, "Cytoplasmic PP2A scaffold."), "PTPN6": note(CAT2, "Cytoplasmic tyrosine phosphatase."), "PYGL": note(CAT2, "Cytosolic glycogen phosphorylase."), "PYGM": note(CAT2_GO, "Cytosolic glycogen phosphorylase."), "RAB1B": note(CAT4, "Prenylated GTPase of the ER-to-Golgi pathway (early secretory compartments)."), "RACK1": note(CAT3B, "RACK1 is a core 40S ribosomal subunit protein as well as a signalling scaffold."), "RPE": note(CAT2_GO, "Cytosolic epimerase."), "RPS3": note(CAT3B, "40S ribosomal protein S3."), "SCAMP3": note(CAT1_GO, "Endosomal/post-Golgi membrane protein. The earlier ACCEPT said SCAMP3 is required for EV " "biogenesis, but the cited work (PMID:19158374, PMID:23418353) shows it regulates ESCRT-dependent " "MVB sorting of EGFR, not EV biogenesis."), "SCGB1A1": ("MARK_AS_OVER_ANNOTATED", "Secreted uteroglobin (UniProt). MISEV2018 (PMID:30637094) category 5 " "allows such proteins onto EVs through specific or promiscuous (proteoglycan, lipid) receptors on the EV " "surface, but asks that their identification be backed by evidence of that association. A bulk EV " "proteome cannot separate surface binding from co-isolation. SCGB1A1 does bind phosphatidylcholine and " "phosphatidylinositol (UniProt), but as ligands held in the central hydrophobic cavity of its " "antiparallel homodimer (PubMed:7664082); no binding to membrane surfaces is recorded, so this is " "ligand sequestration, not the EV-surface route. The earlier ACCEPT rested on prostate expression, " "which does not establish EV association."), "SERINC5": note(CAT1, "Plasma-membrane multipass protein."), "SGSH": note(CAT5, "Soluble lysosomal sulfamidase."), "SHMT1": note(CAT2, "Cytoplasmic serine hydroxymethyltransferase."), "SHMT2": note(CAT4, "Mitochondrial serine hydroxymethyltransferase."), "SLC22A5": note(CAT1, "Apical plasma-membrane carnitine transporter."), "SLC25A1": note(CAT4, "Mitochondrial inner-membrane carrier."), "SLC25A3": note(CAT4, "Mitochondrial inner-membrane carrier."), "SLC3A1": note(CAT1, "Apical plasma-membrane transporter subunit."), "SMS": note(CAT2_GO, "Cytosolic spermine synthase."), "STOM": note(CAT1, "Peripheral plasma-membrane raft protein (stomatin), released in microvesicles; expected EV " "content but not its core location, so the earlier ACCEPT is downgraded. Applies to the plasma " "microvesicle row too."), "SYNE2": note(CAT4_SURFACE, "Nuclear-envelope (outer nuclear membrane) protein; lamellipodium and filopodium " "membrane pool by IDA (PMID:15671068). The earlier reason noted that a peptide-level hit on " "this giant protein does not show which isoform was detected; SYNE2 has many short " "isoforms, and the surface pool belongs to the protein, so the point does not change " "the call."), "TAX1BP1": note(CAT2, "Cytoplasmic autophagy adaptor."), "THBS1": note(CAT5_BOUND, "Secreted thrombospondin-1 with experimental heparin and phosphatidylserine binding (IDA); the earlier ACCEPT rested only on its being secreted."), "THBS4": note(CAT5_BOUND, "Secreted thrombospondin-4 with experimental heparin binding (IDA); the earlier ACCEPT rested only on its being secreted."), "TKFC": note(CAT2_GO, "Cytosolic kinase."), "TKT": note(CAT2_GO, "Cytosolic transketolase."), "TMEM63A": note(CAT1, "Lysosome/endosome membrane channel."), "TOLLIP": note(CAT2, "Cytoplasmic/endosomal adaptor."), "UFC1": note(CAT2_GO, "Cytosolic E2 enzyme."), "UGGT1": note(CAT4, "ER-lumenal glucosyltransferase with an ER-retrieval signal."), "UGP2": note(CAT2, "Cytoplasmic UDP-glucose pyrophosphorylase."), "VPS4A": note(CAT2A, "ESCRT AAA ATPase acting on the cytosolic face of endosomes; the exosome is a destination, " "not where it acts."), "VPS4B": note(CAT2A, "ESCRT AAA ATPase acting on the cytosolic face of endosomes; the exosome is a destination, " "not where it acts."), } # Rows taken over by a later, separate review on main; recorded in decisions.yaml, not edited. SUPERSEDED = { "CD2AP": "ai4curation/ai-gene-review#4287 re-reviewed both rows (UNDECIDED pending the source tables)", } # Per-row overrides where a protein's rows differ in sample and the basis should say so. _ALB = "Serum albumin, which MISEV2018 (PMID:30637094) names as a negative marker for EVs from plasma, serum and serum-containing culture." R = { ("ALB", 52): note(CAT3, f"{_ALB} Here, urinary exosomes, where filtered plasma albumin is abundant."), ("ALB", 53): note(CAT3, f"{_ALB} Here, exosomes from cultured B cells, where serum albumin in the medium is a recognised co-isolate."), ("ALB", 54): note(CAT3, f"{_ALB} Here, exosomes from cultured trabecular meshwork cells, where serum albumin in the medium is a recognised co-isolate."), ("ALB", 55): note(CAT3, f"{_ALB} Here, exosomes from expressed prostatic secretions in urine."), ("APOB", 146): note(CAT3, "Apolipoprotein B, which MISEV2018 (PMID:30637094) names as a negative marker. Here, " "exosomes from expressed prostatic secretions in urine: APOB-containing lipoproteins are " "large and are not normally filtered into urine, so this detection is more likely " "co-isolated plasma or seminal-fluid material than EV cargo."), ("ALB", 57): note(CAT3, f"{_ALB} Here, microvesicles isolated from plasma, the sample MISEV's marker is meant for."), } # supported_by entries that argued for the action this review overturned (a previous # reviewer's own judgement rather than evidence); dropped from the row. S = { ("ARF1", 44): ["file:human/ARF1/ARF1-notes.md"], ("ARF1", 50): ["file:human/ARF1/ARF1-notes.md"], ("ARF1", 51): ["file:human/ARF1/ARF1-notes.md"], }