{"database":"Pride","file_versions":[{"headers":{"Content-Type":["application/json"]},"body":{"files":{"Txt":["ftp://ftp.pride.ebi.ac.uk/pride/data/archive/2026/08/PXD079783/checksum.txt"],"Raw":["ftp://ftp.pride.ebi.ac.uk/pride/data/archive/2026/08/PXD079783/eb03428_20210313141124_JV256_proteome.raw","ftp://ftp.pride.ebi.ac.uk/pride/data/archive/2026/08/PXD079783/eb03383_JV256_phos.raw","ftp://ftp.pride.ebi.ac.uk/pride/data/archive/2026/08/PXD079783/eb03426_20210313121823_JV256_proteome.raw","ftp://ftp.pride.ebi.ac.uk/pride/data/archive/2026/08/PXD079783/eb03384_JV256_phos.raw"],"Mzid":["ftp://ftp.pride.ebi.ac.uk/pride/data/archive/2026/08/PXD079783/eb03426_20210313121823_JV256_proteome.mzid","ftp://ftp.pride.ebi.ac.uk/pride/data/archive/2026/08/PXD079783/eb03383_JV256_phos.mzid","ftp://ftp.pride.ebi.ac.uk/pride/data/archive/2026/08/PXD079783/eb03428_20210313141124_JV256_proteome.mzid","ftp://ftp.pride.ebi.ac.uk/pride/data/archive/2026/08/PXD079783/eb03384_JV256_phos.mzid"],"Other":["ftp://ftp.pride.ebi.ac.uk/pride/data/archive/2026/08/PXD079783/eb03426_20210313121823_JV256_proteome","ftp://ftp.pride.ebi.ac.uk/pride/data/archive/2026/08/PXD079783/eb03428_20210313141124_JV256_proteome","ftp://ftp.pride.ebi.ac.uk/pride/data/archive/2026/08/PXD079783/eb03383_JV256_phos","ftp://ftp.pride.ebi.ac.uk/pride/data/archive/2026/08/PXD079783/eb03384_JV256_phos"]},"type":"primary"},"statusCode":"OK","statusCodeValue":200}],"scores":null,"additional":{"labhead_mail":["sheltzer@stanford.edu"],"submitter":["Lu Qiao"],"technology_type":["Data-dependent acquisition","Mass Spectrometry"],"disease":["Skin Melanoma"],"software":["Not available"],"submitter_keywords":["Splicing","Cdk11","Cell cycle","Kinase inhibitor","Ots964"],"full_dataset_link":["https://www.ebi.ac.uk/pride/archive/projects/PXD079783"],"tissue":["Melanocyte","Skin"],"sample_protocol":["Sample preparation for mass spectrometry  Proteomes were extracted using a buffer containing 200 mM EPPS pH 8.5, 8M urea, 0.1% SDS and protease/phosphatase inhibitors. Following lysis, 150 µg of each proteome was reduced with 5 mM TCEP. Cysteine residues were alkylated using 10 mM iodoacetamide for 20 minutes at RT in the dark. Excess iodoacetamide was quenched with 10 mM DTT. A buffer exchange was carried out using a modified SP3 protocol. Briefly, ∼1500 µg of Cytiva SpeedBead Magnetic Carboxylate Modified Particles (65152105050250 and 4515210505250), mixed at a 1:1 ratio, were added to each sample. 100% ethanol was added to each sample to achieve a final ethanol concentration of at least 50%. Samples were incubated with gentle shaking for 15 minutes. Samples were washed three times with 80% ethanol. Protein was eluted from SP3 beads using 200 mM EPPS pH 8.5 containing Lys-C (Wako, 129-02541). Samples were digested overnight at room temperature with vigorous shaking. The next morning trypsin was added to each sample and further incubated for 6 hours at 37° C. Acetonitrile was added to each sample to achieve a final concentration of ∼33%. Each sample was labelled, in the presence of SP3 beads, with ∼300 µg of TMTPro reagents. Following confirmation of satisfactory labelling (>97%), excess TMT was quenched by addition of hydroxylamine to a final concentration of 0.3%. The full volume from each sample was pooled and acetonitrile was removed by vacuum centrifugation for 1 hour. The pooled sample was acidified and peptides were de-salted using a Sep-Pak 50mg tC18 cartridge (Waters). Peptides were eluted in 70% acetonitrile, 1% formic acid and dried by vacuum centrifugation.  Phosphopeptide enrichment  A phosphopeptide enrichment was performed using a High-Select Fe-NTA Phosphopeptide Enrichment Kit (Thermo Fisher Scientific). Dried phosphopeptides were de-salted by Stage-Tip and re-dissolved in 5% formic acid/5% acetonitrile for LC-MS/MS. The flow through from the phosphopeptide enrichment was used for total proteome profiling.  Basic pH reversed-phase separation (BPRP)  TMT labeled peptides were solubilized in 5% acetonitrile/10 mM ammonium bicarbonate, pH 8.0 and ∼300 µg of TMT labeled peptides were separated by an Agilent 300 Extend C18 column (3.5 µm particles, 4.6 mm ID and 250 mm in length). An Agilent 1260 binary pump coupled with a photodiode array (PDA) detector (Thermo Scientific) was used to separate the peptides. A 45 minute linear gradient from 10% to 40% acetonitrile in 10 mM ammonium bicarbonate pH 8.0 (flow rate of 0.6 mL/min) separated the peptide mixtures into a total of 96 fractions (36 seconds). A total of 96 fractions were consolidated into 24 samples in a checkerboard fashion and vacuum dried to completion. Each sample was desalted via Stage Tips and re-dissolved in 5% formic acid/ 5% acetonitrile for LC-MS/MS analysis.  Liquid chromatography separation and tandem mass spectrometry (LC-MS2)  Total proteome and phosphorylation data were collected using an Orbitrap Eclipse mass spectrometer (Thermo Fisher Scientific) coupled to a Proxeon EASY-nLC 1000 LC pump (Thermo Fisher Scientific). Peptides were separated using a 90 or 120 min gradient at 500-550 nL/min on a 35 cm column (i.d. 100 μm, Accucore, 2.6 μm, 150 Å) packed in-house. A FAIMS device was enabled during data acquisition with compensation voltages set as −40, −60, and −80 V for the total proteome samples and the phosphopeptide-enriched samples. Phosphopeptide-enriched samples were subjected to a second run in which the compensation voltages were set to −45 and −65 V. For total proteome analysis, MS1 data were collected in the Orbitrap (60,000 resolution; maximum injection time set to auto; AGC 4 × 105). Charge states between 2 and 6 were required for MS2 analysis, and a 90 second dynamic exclusion window was used. Cycle time was set at 1 second. MS2 scans were performed in the Orbitrap with HCD fragmentation (isolation window 0.5 Da; 50,000 resolution; NCE 36%; maximum injection time 86 ms; AGC 1 × 105). For phosphopeptide analysis, MS1 data were collected in the Orbitrap (120,000 resolution; maximum injection time set to auto; AGC 4 × 105). Charge states between 2 and 5 were required for MS2 analysis, and a 120 second dynamic exclusion window was used. Cycle time was set at 1 second. MS2 scans were performed in the Orbitrap with HCD fragmentation (isolation window 0.5 Da; 50,000 resolution; NCE 36%; maximum injection time 250 ms; AGC 1.5 × 105)."],"repository":["Pride"],"quantification_method":[""],"modification":[""],"data_protocol":["Data analysis  Raw files were converted to mzXML, and monoisotopic peaks were re-assigned using Monocle. Searches were performed using the Comet search algorithm against a human database downloaded from Uniprot in February 2014. We used a 50 ppm precursor ion tolerance, fragment ion tolerance of 0.02, and a fragment bin offset of 0.0 for MS2 scans collected in the Orbitrap. TMTpro on lysine residues and peptide N-termini (+304.2071 Da) and carbamidomethylation of cysteine residues (+57.0215 Da) were set as static modifications, while oxidation of methionine residues (+15.9949 Da) was set as a variable modification. For phosphorylated peptide analysis, +79.9663 Da was set as a variable modification on serine, threonine, and tyrosine residues.  Each run was filtered separately to 1% False Discovery Rate (FDR) on the peptide-spectrum match (PSM) level. Then proteins were filtered to the target 1% FDR level across the entire combined dataset. Phosphorylation site localization was determined using the AScorePro algorithm. For reporter ion quantification, a 0.003 Da window around the theoretical m/z of each reporter ion was scanned, and the most intense m/z was used. Reporter ion intensities were adjusted to correct for isotopic impurities of the different TMTpro reagents according to manufacturer specifications. Peptides were filtered to include only those with a summed signal-to-noise (SN) ≥ 160 across all TMT channels. An extra filter of an isolation specificity (“isolation purity”) of at least 0.5 in the MS1 isolation window was applied for the phosphorylated peptide analysis. For each protein or phosphorylation site, the filtered peptide TMTpro SN values were summed to generate protein or phosphorylation site quantification values. The signal-to-noise (S/N) measurements of peptides assigned to each protein were summed (for a given protein). These values were normalized so that the sum of the signal for all proteins in each channel was equivalent thereby accounting for equal protein loading. The resulting normalization factors were used to normalize the phosphorylation sites, again to account for equal protein loading."],"omics_type":["Proteomics"],"labhead":["Jason Sheltzer"],"instrument_platform":[""],"labhead_affiliation":["Stanford Cancer Institute, Stanford University"],"submission_type":["COMPLETE"],"species":["Homo Sapiens (human)"],"publication":["40766692 Julian L, Crozier L, Lukow D, Mishra S, Swamy A, Hagenson RA, Sennhenn P, Sausville EL, Mendelson B, Chuaqui C, Qiao L, Vasudevan A, Lin KT, Bhatia S, Bertomeu T, Chatr-Aryamontri A, Zhang L, Rees MG, Ronan MM, Roth JA, Nottoli T, Bai S, Lakshmipathi J, Muthusamy V, Van Vranken JG, Gygi SP, Thompson SL, Smith JC, Anderson K, Shah S, Bindra RS, Akerman M, Spector DL, Krainer AR, Sheltzer JM. On-target toxicity limits the efficacy of CDK11 inhibition against cancers with 1p36 deletions. bioRxiv. 2025:2025.08.03.668359 10.1101/2025.08.03.668359"],"submitter_mail":["luqiao@stanford.edu"],"submitter_affiliation":["Stanford University"],"submitter_country":["United States"],"doi":["10.6019/PXD079783"],"pubmed_abstract":["The cyclin-dependent kinase CDK11 is an understudied kinase that has been the subject of conflicting reports regarding its function in cancer. Here, we combine genetic and pharmacological approaches to demonstrate that CDK11 is a critical regulator of cancer cell survival that is required for RNA splicing and the expression of homologous recombination genes. Inhibition of CDK11 disrupts genome stability, promotes the retention of intronic sequences in mature mRNAs, and induces synthetic lethality with PARP inhibitors. Through integrative analysis of functional genomics datasets, we identify heterozygous deletions of chromosome 1p36 - which encompasses CDK11 and its activating cyclin CCNL2 - as a recurrent and predictive biomarker of sensitivity to CDK11 inhibition. To assess the therapeutic potential of CDK11, we develop MEL-495R, a selective and orally bioavailable CDK11 inhibitor. Additionally, we establish a genetically-engineered mouse model that allows us to differentiate between the on-target and off-target effects of CDK11 inhibitors <i>in vivo</i>. Using this platform, we demonstrate that MEL-495R induces widespread on-target toxicity, revealing a narrow therapeutic index. Together, these findings define CDK11 as a core cancer dependency, uncover a chromosomal deletion that sensitizes tumors to CDK11 inhibition, and provide a generalizable strategy for deconvolving drug efficacy and toxicity <i>in vivo</i> for novel oncology targets."],"pubmed_title":["On-target toxicity limits the efficacy of CDK11 inhibition against cancers with 1p36 deletions."],"pubmed_authors":["Julian Linda L, Crozier Lisa L, Lukow Devon D, Mishra Sanat S, Swamy Aditi A, Hagenson Ryan A RA, Sennhenn Peter P, Sausville Erin L EL, Mendelson Brianna B, Chuaqui Claudio C, Qiao Lu L, Vasudevan Anand A, Lin Kuan-Ting KT, Bhatia Sonam S, Bertomeu Thierry T, Chatr-Aryamontri Andrew A, Zhang Li L, Rees Matthew G MG, Ronan Melissa M MM, Roth Jennifer A JA, Nottoli Timothy T, Bai Suxia S, Lakshmipathi Jayalakshmi J, Muthusamy Viswanathan V, Van Vranken Jonathan G JG, Gygi Steven P SP, Thompson Sarah L SL, Smith Joan C JC, Anderson Kendall K, Shah Sanjana S, Bindra Ranjit S RS, Akerman Martin M, Spector David L DL, Krainer Adrian R AR, Sheltzer Jason M JM"],"additional_accession":[]},"is_claimable":false,"name":"On-target toxicity limits the efficacy of CDK11 inhibition against cancers with 1p36 deletions","description":"The cyclin-dependent kinase CDK11 is an understudied kinase that has been the subject of conflicting reports regarding its function in cancer. Here, we combine genetic and pharmacological approaches to demonstrate that CDK11 is a critical regulator of cancer cell survival that is required for RNA splicing and the expression of homologous recombination genes. Inhibition of CDK11 disrupts genome stability, promotes the retention of intronic sequences in mature mRNAs, and induces synthetic lethality with PARP inhibitors. Through integrative analysis of functional genomics datasets, we identify heterozygous deletions of chromosome 1p36 - which encompasses CDK11 and its activating cyclin CCNL2 - as a recurrent and predictive biomarker of sensitivity to CDK11 inhibition. To assess the therapeutic potential of CDK11, we develop MEL-495R, a selective and orally bioavailable CDK11 inhibitor. Additionally, we establish a genetically-engineered mouse model that allows us to differentiate between the on-target and off-target effects of CDK11 inhibitors in vivo. Using this platform, we demonstrate that MEL-495R induces widespread on-target toxicity, revealing a narrow therapeutic index. Together, these findings define CDK11 as a core cancer dependency, uncover a chromosomal deletion that sensitizes tumors to CDK11 inhibition, and provide a generalizable strategy for deconvolving drug efficacy and toxicity in vivo for novel oncology targets.","dates":{"publication":"2026-08-07","submission":"2026-06-17"},"accession":"PXD079783","cross_references":{"TAXONOMY":["NEWT:3555","NEWT:71647","NEWT:330879","NEWT:35554","NCBITaxon:12939","NEWT:32046","NEWT:544496","NEWT:2042546","NEWT:32049","NEWT:1392696","NEWT:259447","NEWT:295546","NCBITaxon:2719036","NEWT:45351","NEWT:445974","NEWT:43179","NEWT:180454","NEWT:5722","NCBITaxon:1280","NEWT:1129","NEWT:309807","NEWT:10245","NEWT:55153","NEWT:309800","NEWT:281395","NEWT:1211601","NEWT:876138","NEWT:44271","NEWT:193516","NEWT:351581","NEWT:43186","NEWT:428146","NEWT:498257","NEWT:10036","NEWT:1590","NEWT:498019","NEWT:1351","NEWT:1438992","NEWT:1352","NEWT:2649997","NEWT:1147161","NEWT:661410","NEWT:638632","NEWT:263737","NEWT:224326","NEWT:1333499","NCBITaxon:79857","NEWT:1096976","NEWT:5702","NEWT:95648","NEWT:1589","NEWT:135622","NEWT:1349","NEWT:35786","NEWT:1580","NEWT:399784","NEWT:96731","NEWT:383379","NEWT:1401257","NEWT:418106","NEWT:10029","NEWT:913645","NEWT:44491","NEWT:641809","NEWT:27933","NEWT:556484","NEWT:317447","NEWT:4688","NEWT:7955","NEWT:7719","NEWT:7959","NEWT:2261","NEWT:868565","NEWT:31156","NEWT:3112","NEWT:79329","NEWT:4442","NEWT:192875","NEWT:1214915","NEWT:12637","NEWT:59729","NEWT:2164133","NEWT:295105","NEWT:108061","NEWT:60711","NEWT:1316931","NEWT:224308","NEWT:3347","NEWT:511145","NEWT:160621","NEWT:212790","NEWT:931281","NEWT:4432","NEWT:5762","NEWT:5763","NEWT:658457","NEWT:1310161","NEWT:77133","NEWT:295358","NEWT:145481","NCBITaxon:79824","NEWT:2246","NEWT:2652724","NEWT:1912919","NEWT:5757","NCBITaxon:4563","NEWT:5755","NEWT:44689","NEWT:44447","NEWT:752555","NEWT:498211","NEWT:5759","NEWT:347256","NEWT:1736231","NEWT:5518","NEWT:398007","NEWT:1527468","NEWT:1392","NEWT:498217","NEWT:498216","NEWT:2242","NEWT:11320","NEWT:286","NEWT:391619","NEWT:246196","NEWT:287","NEWT:246197","NEWT:1367269","NEWT:145458","NEWT:633149","NEWT:1149786","NEWT:10239","NEWT:68895","NEWT:44685","NEWT:161934","NEWT:4897","NEWT:1148","NEWT:5744","NEWT:5508","NEWT:3329","NEWT:5507","NEWT:410661","NEWT:55571","NEWT:35500","NEWT:1235816","NEWT:1140","NCBITaxon:2157","NEWT:1143","NEWT:4896","NEWT:1287689","NEWT:1390","NEWT:11557","NEWT:1094343","NEWT:1462472","NEWT:1336795","NEWT:644042","NEWT:294","NEWT:1773","NEWT:1182590","NEWT:3712","NEWT:82380","NEWT:3711","NEWT:935293","NEWT:375146","NEWT:270643","NEWT:2065263","NEWT:1772","NEWT:118698","NEWT:1616117","NEWT:263","NEWT:118696","NEWT:52283","NEWT:11988","NEWT:284812","NEWT:8175","NEWT:400667","NEWT:43330","NEWT:1603293","NEWT:408169","NEWT:44664","NEWT:47946","NEWT:459758","NEWT:3702","NEWT:1245466","NEWT:243277","NEWT:1246791","NEWT:7067","NEWT:118694","NEWT:586722","NEWT:2850","NEWT:118691","NEWT:33548","NEWT:274","NEWT:7070","NCBITaxon:287","NEWT:408172","NEWT:408170","NEWT:96794","NEWT:3708","NEWT:332648","NEWT:44670","NEWT:536231","NEWT:376219","NEWT:219813","NEWT:1510","NEWT:1436733","NEWT:460519","NEWT:1247411","NEWT:1515","NEWT:572307","NEWT:1432138","NEWT:1424507","NEWT:1194599","NEWT:272844","NEWT:9483","NEWT:333760","NEWT:56636","NEWT:1513458","NEWT:1233681","NCBITaxon:40559","NEWT:506599","NEWT:2853422","NEWT:81077","NEWT:84588","NEWT:1679718","NEWT:480","NEWT:65349","NEWT:67767","NEWT:46835","NEWT:109757","NEWT:582580","NEWT:300852","NEWT:1502","NEWT:128017","NEWT:376686","NEWT:95486","NEWT:508771","NEWT:1883446","NEWT:253","NCBITaxon:2759","NEWT:1233435","NEWT:93061","NEWT:93062","NEWT:34613","NCBITaxon:4932","NEWT:109760","NEWT:943274","NEWT:644223","NEWT:235443","NEWT:108458","NEWT:5936","NEWT:272623","NEWT:272624","NEWT:320637","NEWT:886559","NEWT:55521","NEWT:983964","NEWT:118499","NEWT:11706","NEWT:32644","NEWT:527796","NEWT:1130798","NEWT:55529","NEWT:499175","NEWT:109779","NEWT:3745","NEWT:1715989","NCBITaxon:4751","NEWT:476272","NEWT:3747","NEWT:195051","NEWT:3988","NEWT:1116234","NEWT:1255228","NEWT:649908","NEWT:410289","NEWT:373153","NEWT:3983","NEWT:203696","NEWT:352472","NEWT:1071661","NEWT:1202532","NEWT:360094","NEWT:470","NEWT:41364","NEWT:5911","NEWT:1313","NEWT:1218097","NCBITaxon:50557","NEWT:39251","NEWT:39491","NEWT:212142","NCBITaxon:5811","NEWT:29491","NEWT:101841","NEWT:2014887","NEWT:33952","NEWT:153009","NEWT:261756","NEWT:571256","NEWT:40483","NEWT:63366","NEWT:63367","NEWT:688333","NEWT:215402","NCBITaxon:548681","NEWT:318586","NCBITaxon:5820","NEWT:1547","NEWT:272634","NEWT:198107","NEWT:9031","NEWT:1872122","NEWT:1308","NEWT:7091","NEWT:1034015","NEWT:760568","NEWT:141262","NEWT:108931","NEWT:1055524","NEWT:4087","NEWT:9778","NEWT:306","NEWT:150475","NEWT:303","NEWT:267872","NEWT:97477","NEWT:7111","NEWT:347515","NEWT:172269","NEWT:9534","NEWT:6269","NEWT:5180","NEWT:256737","NEWT:4090","NEWT:4092","NEWT:9541","NEWT:8694","NEWT:4093","NEWT:4096","NEWT:8692","NEWT:2903","NEWT:185579","NEWT:941442","NEWT:536088","NEWT:13076","NEWT:1226408","NEWT:7108","NEWT:40479","NEWT:43989","NEWT:4076","NEWT:142615","NEWT:317","NEWT:1006581","NEWT:885318","NEWT:39488","NEWT:550","NEWT:4081","NEWT:273068","NEWT:554","NEWT:98334","NEWT:451516","NEWT:552","NEWT:4084","NEWT:63577","NEWT:36185","NEWT:1225786","NEWT:7574","NEWT:1715256","NEWT:30640","NEWT:575412","NEWT:929793","NEWT:29204","NEWT:28112","NEWT:114155","NEWT:6494","NEWT:6491","NEWT:507601","NEWT:520","NEWT:186441","NEWT:634955","NEWT:643680","NEWT:214092","NCBITaxon:6157","NEWT:6239","NEWT:13095","NEWT:162425","NEWT:216257","NEWT:102169","NEWT:208893","NEWT:9986","NEWT:4054","NEWT:8654","NEWT:8658","NEWT:1268063","NEWT:8657","NEWT:8655","NEWT:5147","NEWT:98351","NEWT:1263854","NEWT:118503","NEWT:2059687","NEWT:160488","NEWT:28104","NEWT:207559","NEWT:407821","NCBITaxon:2","NEWT:85057","NEWT:985076","NEWT:568708","NEWT:1215323","NEWT:986","NEWT:52641","NEWT:7159","NEWT:267671","NEWT:28532","NEWT:353152","NEWT:8496","NEWT:7165","NEWT:1257118","NEWT:27448","NEWT:40674","NEWT:1194669","NEWT:51329","NEWT:243230","NEWT:443906","NEWT:1080772","NEWT:519","NEWT:8479","NEWT:8485","NEWT:6063","NEWT:49240","NEWT:1328388","NEWT:104395","NEWT:9557","NEWT:9315","NEWT:6289","NEWT:377586","NEWT:6287","NEWT:300641","NEWT:727","NEWT:9796","NEWT:9554","NEWT:118562","NEWT:725","NEWT:7137","NEWT:469008","NEWT:256318","NEWT:9321","NEWT:206411","NCBITaxon:6191","NEWT:596153","NEWT:229533","NEWT:1836","NEWT:214053","NCBITaxon:10298","NEWT:80863","NEWT:90675","NEWT:105231","NEWT:104385","NEWT:74649","NEWT:52638","NEWT:57075","NEWT:206672","NEWT:4097","NEWT:8697","NEWT:8695","NEWT:884204","NEWT:71139","NEWT:9785","NEWT:6279","NEWT:1123869","NEWT:9544","NEWT:9545","NEWT:7370","NEWT:9793","NEWT:83906","NCBITaxon:780","NCBITaxon:1502","NEWT:6282","NEWT:1134506","NEWT:255470","NEWT:27457","NEWT:38783","NEWT:4006","NEWT:6426","NCBITaxon:5476","NEWT:113208","NEWT:33090","NEWT:6669","NEWT:9935","NEWT:89453","NEWT:287889","NEWT:1114301","NEWT:51515","NEWT:588596","NEWT:51511","NEWT:8845","NEWT:92867","NEWT:92866","NEWT:419610","NEWT:5334","NEWT:51750","NEWT:202950","NEWT:382352","NEWT:413071","NCBITaxon:10239","NCBITaxon:714","NEWT:295027","NCBITaxon:11320","NEWT:632957","NEWT:11051","NEWT:9925","NEWT:89462","NCBITaxon:9606","NEWT:452680","NEWT:8839","NEWT:90690","NEWT:1436183","NEWT:4232","NEWT:2758385","NEWT:416348","NEWT:11298","NEWT:171101","NEWT:714","NEWT:5322","NEWT:421932","NEWT:312017","NEWT:196627","NEWT:200308","NEWT:553470","NEWT:200302","NEWT:870435","NEWT:284593","NEWT:100392","NEWT:655819","NEWT:5315","NEWT:9913","NEWT:265872","NEWT:105841","NEWT:337330","NEWT:2666255","NEWT:2285","NEWT:2287","NEWT:999810","NCBITaxon:5693","NEWT:28995","NEWT:1392998","NEWT:380394","NEWT:981087","NEWT:180066","NEWT:226900","NEWT:1266738","NEWT:231490","NEWT:244704","NEWT:7725","NEWT:430615","NEWT:563041","NEWT:72664","NEWT:174633","NEWT:326423","NEWT:452467","NEWT:198822","NEWT:36111","NEWT:326424","NEWT:1416333","NEWT:35024","NEWT:135461","NEWT:1678078","NEWT:7962","NEWT:749906","NEWT:418985","NEWT:1817808","NEWT:749907","NEWT:145262","NEWT:145263","NEWT:431947","NEWT:69014","NEWT:142809","NEWT:694569","NEWT:27606","NEWT:9739","NEWT:59202","NEWT:9975","NEWT:8643","NEWT:51953","NEWT:502780","NEWT:57267","NEWT:3197","NEWT:860688","NEWT:13443","NEWT:8644","NEWT:36329","NEWT:62615","NEWT:5141","NEWT:46360","NCBITaxon:3044782","NEWT:1333550","NEWT:160235","NEWT:72407","NEWT:8639","NEWT:1928434","NEWT:8637","NEWT:349741","NEWT:1114970","NEWT:409859","NEWT:157295","NEWT:2096","NEWT:509169","NEWT:3051137","NEWT:192222","NEWT:9721","NEWT:137221","NEWT:9963","NEWT:1617910","NEWT:565050","NEWT:409860","NEWT:2785785","NEWT:411901","NEWT:8626","NEWT:105884","NCBITaxon:9615","NEWT:8621","NEWT:58334","NEWT:452659","NEWT:1193501","NEWT:58331","NEWT:6689","NEWT:8624","NEWT:5116","NEWT:8623","NEWT:5597","NCBITaxon:3077","NEWT:298315","NEWT:8618","NEWT:70448","NEWT:9704","NEWT:698936","NEWT:1009874","NEWT:8855","NEWT:9940","NEWT:3168","NEWT:1247190","NEWT:521001","NEWT:192011","NEWT:1813887","NEWT:118702","NEWT:118700","NEWT:2126719","NEWT:224911","NEWT:118705","NCBITaxon:11552","NEWT:334249","NEWT:6945","NEWT:184922","NEWT:6703","NEWT:2104","NEWT:6943","NEWT:2","NEWT:157546","NEWT:35670","NEWT:511693","NEWT:870726","NEWT:474186","NEWT:38942","NEWT:35677","NEWT:1493","NEWT:307972","NEWT:1496","NEWT:2102","NEWT:3674","NEWT:660469","NEWT:1365186","NEWT:38949","NEWT:45474","NEWT:1299114","NEWT:1590841","NEWT:2282334","NEWT:4513","NEWT:1247","NEWT:70667","NEWT:869728","NEWT:5843","NEWT:6938","NEWT:376741","NCBITaxon:39054","NCBITaxon:10407","NEWT:1736309","NEWT:4751","NEWT:10360","NEWT:47664","NEWT:317548","NEWT:15819","NEWT:3654","NEWT:237561","NEWT:1085956","NEWT:5833","NEWT:3659","NEWT:6928","NEWT:1239","NEWT:36745","NEWT:499229","NEWT:31298","NEWT:400727","NEWT:1204162","NEWT:272563","NEWT:11009","NEWT:82688","NEWT:5823","NEWT:3885","NEWT:3888","NEWT:5821","NEWT:44139","NEWT:649408","NCBITaxon:4895","NCBITaxon:4896","NEWT:315393","NEWT:6915","NEWT:3649","NEWT:101510","NEWT:28903","NEWT:3880","NEWT:272559","NEWT:216816","NEWT:28909","NEWT:515849","NEWT:3641","NEWT:10141","NEWT:466585","NEWT:1000589","NEWT:85963","NEWT:85962","NEWT:42197","NEWT:143361","NCBITaxon:5796","NEWT:12993","NEWT:398580","NEWT:4565","NEWT:1264690","NEWT:515619","NEWT:1299","NEWT:316407","NEWT:34305","NCBITaxon:183674","NEWT:167387","NEWT:84645","NEWT:44586","NEWT:1123294","NEWT:626528","NEWT:139927","NEWT:4558","NEWT:209285","NEWT:5888","NEWT:211586","NEWT:747078","NEWT:1282","NEWT:1283","NEWT:431241","NEWT:4550","NEWT:1000561","NEWT:2133","NEWT:4555","NEWT:294381","NEWT:197","NEWT:1390363","NEWT:35889","NEWT:406072","NEWT:144030","NEWT:288705","NEWT:29176","NEWT:4787","NEWT:3217","NEWT:113549","NEWT:4547","NEWT:3218","NEWT:556182","NEWT:1270","NEWT:374990","NEWT:1432059","NEWT:154293","NEWT:156471","NEWT:4784","NEWT:3694","NEWT:360106","NEWT:156476","NEWT:4543","NEWT:4785","NEWT:210007","NEWT:360104","NEWT:1857017","NEWT:10117","NEWT:10359","NEWT:10116","NEWT:1280","NEWT:10358","NEWT:83333","NEWT:1735272","NEWT:83334","NEWT:83332","NEWT:317513","NEWT:580240","NEWT:294128","NEWT:11676","NEWT:100226","NEWT:718308","NEWT:4530","NEWT:176299","NEWT:5861","NEWT:54126","NEWT:75058","NEWT:13616","NEWT:172","NEWT:296543","NEWT:173","NEWT:316435","NEWT:42157","NEWT:1895","NEWT:1034304","NEWT:105023","NEWT:866628","NEWT:215358","NEWT:64152","NEWT:4924","NEWT:749200","NEWT:2748","NEWT:8049","NEWT:33892","NEWT:9378","NEWT:990346","NEWT:145953","NEWT:257309","NEWT:100816","NEWT:203124","NEWT:192952","NEWT:230741","NEWT:8296","NEWT:117008","NCBITaxon:1313","NEWT:167748","NEWT:1163394","NEWT:44544","NEWT:529818","NEWT:400540","NEWT:4911","NEWT:645463","NEWT:152480","NEWT:129249","NEWT:1077286","NEWT:943129","NEWT:1221594","NEWT:990119","NEWT:77216","NEWT:1111708","NEWT:227321","NEWT:493760","NEWT:281677","NEWT:106590","NEWT:260710","NEWT:257313","NEWT:3827","NEWT:400772","NEWT:128161","NEWT:930945","NEWT:1162296","NEWT:106592","NEWT:46704","NEWT:482428","NEWT:1187947","NEWT:269796","NEWT:10312","NCBITaxon:1773","NEWT:54571","NEWT:9598","NEWT:8030","NEWT:1423772","NEWT:53232","NEWT:1235987","NEWT:1639","NEWT:188229","NEWT:246437","NEWT:3818","NEWT:4909","NEWT:759272","NEWT:432359","NEWT:1182263","NEWT:943146","NEWT:2711","NEWT:537457","NEWT:479249","NEWT:9103","NEWT:715877","NEWT:862238","NEWT:29159","NEWT:10306","NEWT:9595","NEWT:8022","NEWT:145943","NEWT:595536","NEWT:240906","NEWT:593117","NEWT:89920","NEWT:29158","NEWT:3633","NEWT:3635","NEWT:5811","NEWT:3879","NEWT:180923","NEWT:1328881","NEWT:411483","NEWT:76336","NEWT:3870","NEWT:884019","NEWT:198215","NEWT:411490","NEWT:200298","NEWT:169963","NEWT:1400870","NEWT:587","NEWT:588","NEWT:585","NEWT:343","NCBITaxon:43925","NEWT:225117","NEWT:746128","NEWT:5801","NEWT:43665","NEWT:212035","NEWT:5802","NCBITaxon:1653394","NEWT:1266464","NEWT:1205","NEWT:214693","NEWT:367830","NEWT:178616","NEWT:95145","NEWT:375451","NEWT:357","NEWT:9172","NEWT:2770979","NEWT:2010198","NEWT:1277351","NEWT:1594786","NEWT:457428","NEWT:106178","NEWT:411469","NEWT:84023","NEWT:1679","NEWT:559292","NEWT:569","NEWT:411464","NEWT:411460","NEWT:2762","NEWT:1174673","NEWT:1328426","NEWT:562","NEWT:28035","NEWT:411470","NEWT:2094720","NCBITaxon:2697049","NCBITaxon:138","NEWT:28038","NEWT:1663","NEWT:62141","NEWT:1423","NEWT:4932","NEWT:3603","NEWT:2756","NEWT:2759","NEWT:3848","NEWT:3847","NEWT:38293","NEWT:1428","NEWT:339","NEWT:327159","NEWT:178876","NEWT:1660","NEWT:2751","NEWT:327160","NEWT:573","NEWT:571","NEWT:12922","NEWT:29595","NEWT:1306413","NEWT:241368","NEWT:518766","NEWT:42528","NEWT:2664373","NEWT:190802","NEWT:9417","NEWT:1216979","NEWT:7237","NEWT:264483","NEWT:509924","NEWT:28450","NEWT:115104","NEWT:1121114","NEWT:663","NEWT:8570","NEWT:1081927","NEWT:1238993","NEWT:67825","NEWT:187878","NEWT:1241935","NEWT:220668","NEWT:1821314","NEWT:1249668","NEWT:426430","NEWT:38033","NEWT:9407","NEWT:9646","NEWT:5286","NEWT:7227","NEWT:7469","NEWT:9402","NEWT:9644","NEWT:415540","NEWT:675060","NEWT:334542","NEWT:313625","NEWT:27592","NEWT:426428","NEWT:227289","NEWT:63459","NEWT:1276815","NEWT:40324","NEWT:588858","NEWT:9638","NEWT:9639","NCBITaxon:11071","NEWT:242231","NEWT:197221","NEWT:7215","NEWT:51453","NEWT:2172103","NCBITaxon:59201","NEWT:7460","NEWT:504457","NEWT:434271","NEWT:392227","NEWT:747679","NEWT:66712","NEWT:42752","NEWT:103372","NEWT:746360","NEWT:862751","NEWT:89764","NEWT:470150","NEWT:9627","NEWT:543734","NEWT:1009714","NEWT:73239","NEWT:38018","NEWT:226186","NEWT:9870","NEWT:8782","NEWT:115357","NEWT:435590","NEWT:1902","NEWT:63436","NEWT:1908","NEWT:1169740","NEWT:13164","NEWT:216129","NEWT:2664179","NEWT:623","NEWT:7038","NEWT:6192","NCBITaxon:1639","NCBITaxon:38727","NEWT:74790","NEWT:2829","NEWT:366581","NEWT:216599","NEWT:405534","NEWT:216595","NEWT:40559","NEWT:51208","NEWT:216597","NEWT:9689","NEWT:8355","NEWT:633","NEWT:1607839","NEWT:9685","NEWT:7029","NEWT:6182","NEWT:1283300","NEWT:9694","NEWT:186990","NEWT:632","NEWT:1204551","NEWT:6183","NEWT:99586","NEWT:630","NCBITaxon:11019","NEWT:334747","NEWT:61235","NEWT:392021","NEWT:343691","NEWT:1457551","NEWT:15368","NEWT:1491466","NEWT:436486","NEWT:340188","NEWT:51655","NEWT:170187","NEWT:260707","NEWT:121845","NEWT:8595","NEWT:7263","NEWT:186763","NEWT:185431","NEWT:216591","NEWT:29760","NEWT:260704","NEWT:1719","NEWT:703612","NEWT:260705","NEWT:1202347","NEWT:692672","NEWT:2697049","NEWT:1505907","NEWT:1216981","NEWT:1109443","NEWT:1249885","NEWT:7004","NEWT:1972855","NEWT:9669","NCBITaxon:6073","NEWT:1089448","NEWT:1415167","NEWT:1329349","NEWT:607699","NEWT:208963","NEWT:208964","NEWT:27337","NEWT:575584","NEWT:185687","NEWT:3039","NEWT:669202","NEWT:2706014","NEWT:8727","NEWT:8726","NEWT:10090","NEWT:8729","NEWT:4120","NEWT:8720","NEWT:5693","NEWT:2186","NEWT:8724","NEWT:8723","NEWT:283166","NEWT:37334","NEWT:5697","NEWT:6544","NCBITaxon:10357","NCBITaxon:10114","NCBITaxon:10359","NEWT:1685931","NEWT:1203258","NEWT:242619","NEWT:49317","NEWT:557723","NEWT:557722","NEWT:160791","NEWT:1353008","NEWT:34073","NEWT:696811","NEWT:402042","NEWT:373995","NEWT:5689","NEWT:8715","NEWT:839","NEWT:544404","NEWT:92519","NEWT:2173","NEWT:943925","NEWT:37349","NEWT:4113","NEWT:837","NEWT:640459","NEWT:36015","NEWT:1232801","NEWT:81866","NEWT:5691","NEWT:48479","NEWT:61435","NEWT:627025","NEWT:1097677","NEWT:375939","NEWT:61674","NEWT:2072580","NEWT:669465","NEWT:1117957","NEWT:6526","NEWT:8709","NEWT:4100","NEWT:1159556","NEWT:5671","NEWT:1076","NEWT:4102","NEWT:4101","NEWT:6763","NEWT:8700","NEWT:803","NEWT:29722","NEWT:1692259","NEWT:1486917","NEWT:419947","NEWT:468911","NEWT:13373","NEWT:817","NEWT:7604","NEWT:818","NEWT:135588","NEWT:1843183","NEWT:5661","NEWT:157592","NEWT:51866","NEWT:29719","NEWT:58002","NEWT:5665","NEWT:6754","NEWT:1179777","NEWT:6997","NEWT:452589","NEWT:509068","NEWT:5666","NEWT:4577","NEWT:813","NEWT:5664","NEWT:2157","NEWT:146479","NEWT:1042986","NEWT:1911079","NEWT:69373","NEWT:1843192","NEWT:206189","NEWT:427577","NEWT:264203","NEWT:1480154","NEWT:1274414","NEWT:9612","NEWT:38626","NEWT:1286640","NEWT:38865","NEWT:3077","NEWT:9615","NEWT:10299","NEWT:6100","NEWT:713604","NEWT:112273","NEWT:1147787","NEWT:1440772","NEWT:10040","NEWT:1355477","NEWT:8759","NEWT:9605","NEWT:9606","NEWT:90371","NEWT:641501","NEWT:4153","NEWT:9601","NEWT:278839","NEWT:35128","NEWT:39966","NEWT:7668","NEWT:8756","NEWT:915099","NEWT:74940","NEWT:13551","NEWT:10041","NEWT:9600","NEWT:1450511","NEWT:1143193","NEWT:1122233","NEWT:890382","NEWT:174934","NEWT:179392","NEWT:2823525","NEWT:115778","NEWT:9838","NEWT:9839","NEWT:546414","NEWT:227086","NEWT:3055","NEWT:11167","NEWT:9835","NEWT:7650","NEWT:4146","NEWT:5478","NEWT:6326","NEWT:7656","NEWT:5476","NEWT:1450520","NEWT:1042311","NEWT:1123352","NEWT:1882945","NEWT:746707","NEWT:299767","NEWT:235909","NEWT:28835","NEWT:47311","NEWT:1274432","NEWT:2053667","NEWT:1274426","NEWT:104660","NEWT:9825","NEWT:1274423","NEWT:393765","NEWT:652611","NEWT:39946","NEWT:9823","NEWT:95602","NEWT:8732","NEWT:314539","NEWT:39947","NEWT:718274","NEWT:1274420","NEWT:578458","NEWT:60520"],"pubmed":["40766692"]}}