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Table S1. Clinicopathological Characterization of 99 Leiomyosarcoma Cases. STT Lib.Name Location Grade

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Table S1. Clinicopathological characterization of 99 Leiomyosarcoma cases. Subtypes from Age Prior Consensus Silhouette STT Lib.name Location Grade (years) Sex Relapse therapy Clustering value 5858 STT5858_LMS Uterine Low 51 Female Primary No I 0.125666992 5840 STT5840_LMS Extremities High 58 Female Primary No I 0.113624441 5836 STT5836_LMS Uterine Low 48 Female Primary No I 0.087137194 5859 STT5859_LMS Uterine High 40 Female Primary No I 0.0834868 5977 STT5977_LMS Extremities Low 21 Female Primary No I 0.083093565 5980 STT5980_LMS Thoracic/Abdominal/Retroperitoneal Low 51 Female Primary No I 0.080408626 5528 STT5528_LMS Extremities Intermediate 78 Male Local recur NA I 0.073772216 516 STT516_LMS Thoracic/Abdominal/Retroperitoneal high 68 Female Local recur No I 0.07061551 5841 STT5841_LMS Thoracic/Abdominal/Retroperitoneal High 74 Male Primary No I 0.070152611 6044 STT6044_LMS Thoracic/Abdominal/Retroperitoneal low 42 Female Local recur No I 0.069310086 6027 STT6027_LMS Thoracic/Abdominal/Retroperitoneal low 78 Male Local recur Yes I 0.0611887 6023 STT6023_LMS Thoracic/Abdominal/Retroperitoneal Intermediate 68 Female Met Yes I 0.060305089 6045 STT6045_LMS Extremities Intermediate 56 Male Met Yes I 0.050367868 5862 STT5862_LMS Uterine High 46 Female Primary No I 0.048356007 5976 STT5976_LMS Extremities Intermediate 81 Male Primary No I 0.048039714 5986 STT5986_LMS Thoracic/Abdominal/Retroperitoneal Intermediate 58 Male Primary No I 0.047491088 5846 STT5846_LMS Extremities Intermediate 46 Male Primary No I 0.044706292 6024 STT6024_LMS Unknown Intermediate 44 Female Met Yes I 0.043907123 5860 STT5860_LMS Uterine High 40 Female Met No I 0.043778974 6047 STT6047_LMS Thoracic/Abdominal/Retroperitoneal low 63 Female Local recur No I 0.043567402 5843 STT5843_LMS Extremities High 84 Male Primary No I 0.042812811 5985 STT5985_LMS Thoracic/Abdominal/Retroperitoneal Low 63 Female Primary No I 0.040251958 5851 STT5851_LMS Extremities High 65 Male Local recur No I 0.036103313 5863 STT5863_LMS Uterine High 35 Female Primary No I 0.035922655 5978 STT5978_LMS Extremities High 65 Female Primary No I 0.035346643 6046 STT6046_LMS Uterine Intermediate 53 Female Local recur No I 0.025546256 5855 STT5855_LMS Extremities High 56 Female Primary No I 0.023343122 5861 STT5861_LMS Uterine High 44 Female Primary No I 0.023081575 5975 STT5975_LMS Thoracic/Abdominal/Retroperitoneal Intermediate 52 Male Primary No I 0.016164913 5981 STT5981_LMS Extremities High 73 Male Primary No I 0.015302853 6794 STT6794_LMS Uterine High 55 Female Primary No I 0.013749464 6035 STT6035_LMS Thoracic/Abdominal/Retroperitoneal low 53 Female Primary No I 0.012552951 6036 STT6036_LMS Thoracic/Abdominal/Retroperitoneal low 2 Female Primary No I 0.005798847 6021 STT6021_LMS Extremities high 81 Male Local recur NA I 0.004793186 5842 STT5842_LMS Extremities Intermediate 42 Male Local recur No I 0.00183114 6037 STT6037_LMS Thoracic/Abdominal/Retroperitoneal Intermediate 94 Female Local recur No I ‐0.002303405 5838 STT5838_LMS Uterine High 64 Female Primary No I ‐0.003689111 5849 STT5849_LMS Extremities Low 38 Female Primary No I ‐0.007691372 6093 STT6093_LMS Extremities High 68 Female Primary No I ‐0.016743075 6799 STT6799_LMS Uterine High 57 Female Primary No I ‐0.017815515 6040 STT6040_LMS Thoracic/Abdominal/Retroperitoneal high 45 Female Met No I ‐0.018449475 6779 STT6779_LMS Uterine High 57 Female Primary No I ‐0.019223609 5847 STT5847_LMS Extremities Intermediate 52 Female Local recur No I ‐0.023447131 6028 STT6028_LMS Uterine high 47 Female Local recur Yes I ‐0.026580215 6795 STT6795_LMS Uterine Low 65 Female Primary No I ‐0.035675753 5856 STT5856_LMS Thoracic/Abdominal/Retroperitoneal High 67 Male Primary No I ‐0.036630406 5844 STT5844_LMS Extremities High 85 Male Primary No I ‐0.038219004 6025 STT6025_LMS Uterine high 52 Female Met Yes I ‐0.043624331 6029 STT6029_LMS Uterine high 39 Female Met No I ‐0.053120449 5837 STT5837_LMS Uterine High 55 Female Primary No I ‐0.059455969 5848 STT5848_LMS Extremities High 53 Male Primary No I ‐0.061915752 6096 STT6096_LMS Thoracic/Abdominal/Retroperitoneal High 67 Female Primary No I ‐0.063337165 5845 STT5845_LMS Extremities High 72 Male Primary No I ‐0.068247842 5852 STT5852_LMS Extremities High 60 Female Primary No I ‐0.076071787 5839 STT5839_LMS Extremities High 50 Female Primary No I ‐0.089352234 6798 STT6798_LMS Uterine High 56 Female Primary No I ‐0.096945871 6803 STT6803_LMS Uterine High 54 Female Primary No II 0.201993776 6049 STT6049_LMS Uterine high 44 Female Local recur No II 0.186594445 6802 STT6802_LMS Uterine High 58 Female Primary No II 0.1775918 6038 STT6038_LMS Thoracic/Abdominal/Retroperitoneal Intermediate 48 Male Local recur Yes II 0.16107199 6039 STT6039_LMS Thoracic/Abdominal/Retroperitoneal high 59 Male Local recur No II 0.158447098 6784 STT6784_LMS Uterine High 50 Female Primary No II 0.157304316 6050 STT6050_LMS Thoracic/Abdominal/Retroperitoneal low 67 Female Local recur No II 0.150862931 6788 STT6788_LMS Uterine Low 59 Female Primary No II 0.148595072 6032 STT6032_LMS Extremities high 43 Male Local recur No II 0.1439824 6034 STT6034_LMS Thoracic/Abdominal/Retroperitoneal high 50 Female Local recur No II 0.134235712 6041 STT6041_LMS Uterine Intermediate 47 Female Local recur No II 0.133387215 6805 STT6805_LMS Uterine High 48 Female Primary No II 0.125907512 6043 STT6043_LMS Uterine low 57 Female Local recur Yes II 0.116911639 6801 STT6801_LMS Uterine High 51 Female Primary No II 0.113703303 6030 STT6030_LMS Thoracic/Abdominal/Retroperitoneal Intermediate 57 Female Local recur Yes II 0.108366137 6033 STT6033_LMS Thoracic/Abdominal/Retroperitoneal high 66 Female Local recur No II 0.102841058 6650 STT6650_LMS Uterine High 56 Female Primary No II 0.097045936 6652 STT6652_LMS Uterine High 41 Female Primary No II 0.093357847 6620 STT6620_LMS Thoracic/Abdominal/Retroperitoneal high 63 Male Local recur No II 0.085595688 6806 STT6806_LMS Uterine High 56 Female Primary No II 0.084901255 6022 STT6022_LMS Uterine Intermediate 57 Female Met Yes II 0.077669139 1220 STT1220_LMS Thoracic/Abdominal/Retroperitoneal high 46 Female Local recur No II 0.029450414 6804 STT6804_LMS Uterine Low 60 Female Primary No III 0.262114051 6780 STT6780_LMS Uterine High 47 Female Primary No III 0.250516979 6796 STT6796_LMS Uterine High 46 Female Primary No III 0.245780946 6782 STT6782_LMS Uterine High 65 Female Primary No III 0.243962292 5834 STT5834_LMS Uterine High 57 Female Primary No III 0.241472767 5857 STT5857_LMS Thoracic/Abdominal/Retroperitoneal High 55 Male Primary No III 0.233951621 6775 STT6775_LMS Uterine High 70 Female Primary No III 0.179026041 6778 STT6778_LMS Uterine High 73 Female Primary No III 0.172778217 5835 STT5835_LMS Uterine low 61 Female Primary No III 0.127437241 6789 STT6789_LMS Uterine Low 57 Female Primary No III 0.097159818 6783 STT6783_LMS Uterine High 43 Female Met Yes III 0.060686741 6791 STT6791_LMS Uterine High 69 Female Primary No III 0.015848024 6776 STT6776_LMS Uterine High 80 Female Primary No III 0.002436252 6785 STT6785_LMS Uterine High 42 Female Met No III ‐0.009570967 5979 STT5979_LMS Extremities Intermediate 59 Male Local recur No III ‐0.041675365 6048 STT6048_LMS Uterine Intermediate 54 Female Local recur No III ‐0.051217895 6781 STT6781_LMS Uterine High 68 Female Primary No III ‐0.071479456 5854 STT5854_LMS Extremities High 83 Female Primary No III ‐0.074671556 5853 STT5853_LMS Uterine Intermediate 68 Female Local recur No III ‐0.14943816 6777 STT6777_LMS Uterine High 53 Female Primary No III ‐0.156690731 6651 STT6651_LMS Uterine High 46 Female Primary No III ‐0.22152812 Table S2. Patient clinical features for TCGA dataset (N=82). No. of Patients Percent (%) C3 (subtype I) C1 (subtype II) C2 (subtype III) LMS with Neg sil width Sex Female 43 52% 17 12 6 8 Male 21 26% 14 4 0 3 NA 18 22% 7 5 6 0 Location Uterine 19 23% 2 6 6 5 Thoracic/Abdominal/Retroperitoneal 32 39% 22 5 0 5 Extremities 13 16% 7 5 0 1 NA 18 22% 7 5 6 0 Relapse Primary 80 98% 37 21 11 11 recurent 2 2% 1 0 1 0 Prior therapy Yes 14 17% 5 4 3 2 No 33 40% 20 9 0 4 NA 35 43% 13 8 9 5 Total 82 38 21 12 11 Table S3.The number of overlapping genes by SAMSeq analysis between 3SEQ and TCGA RNASeq datasets. Subtype I‐3SEQ Subtype II‐3SEQ Subtype III‐3SEQ TCGA‐C3 (Subtype I) 2282 870 392 TCGA‐C1 (Subtype II) 1098 2075 230 TCGA‐C2 (Subtype III) 292 297 75 Table S4. Comparison of expression profiles between TCGA subtypes with SAMSeq. TCGA‐C3 (corresponding 3SEQ subtype I) vs. other TCGA subtypes Gene ID Score(d) Fold Change (C3/others) qvalue(%) LMOD1|25802 528.7 13.6986 0 MYLK|4638 402.1 13.5135 0 ACTG2|72 437.25 5.2083 0 CASQ2|845 516.95 166.6667 0 CFL2|1073 546.35 3.8168 0 SLMAP|7871 568.65 7.9365 0 TCGA‐C1 (corresponding 3SEQ subtype II) vs. other TCGA subtypes Gene ID Score(d) Fold Change (C1/others) qvalue(%) ARL4C|10123 436.2 8.333333333 0 Table S5. SAMSeq results between different LMS subtypes in 3SEQ data. Note before read this table: 1. SAMSeq was used to test the significance of differential expression between different LMS subtypes. E.g. "Subtype I vs. Others " is the comparsion between subtype I LMS and other LMS cases. 2. Genes were ranked by the SAMSeq significance, positive value means that this gene is significantly over‐expressed in second group, minus value means that gene is over‐expressed in first group. E.g. gene APLP2 is over‐expressed in Subtype I LMS with rank 5900, is also over‐expressed in Subtyp II iwith rank 3099, but is down‐expressed in Subtype III with rank 1549. 3. Increased absolute values of ranks from rank 1 to 10 (or ‐1 to ‐10), indicate decreased significances. Genes with rank 1 or ‐1 are most significant one from SAMSeq output.
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    ARTICLE Received 11 Dec 2015 | Accepted 13 Oct 2016 | Published 6 Dec 2016 | Updated 5 Jan 2017 DOI: 10.1038/ncomms13542 OPEN Defining functional interactions during biogenesis of epithelial junctions J.C. Erasmus1,*, S. Bruche1,*,w, L. Pizarro1,2,*, N. Maimari1,3,*, T. Poggioli1,w, C. Tomlinson4,J.Lees5, I. Zalivina1,w, A. Wheeler1,w, A. Alberts6, A. Russo2 & V.M.M. Braga1 In spite of extensive recent progress, a comprehensive understanding of how actin cytoskeleton remodelling supports stable junctions remains to be established. Here we design a platform that integrates actin functions with optimized phenotypic clustering and identify new cytoskeletal proteins, their functional hierarchy and pathways that modulate E-cadherin adhesion. Depletion of EEF1A, an actin bundling protein, increases E-cadherin levels at junctions without a corresponding reinforcement of cell–cell contacts. This unexpected result reflects a more dynamic and mobile junctional actin in EEF1A-depleted cells. A partner for EEF1A in cadherin contact maintenance is the formin DIAPH2, which interacts with EEF1A. In contrast, depletion of either the endocytic regulator TRIP10 or the Rho GTPase activator VAV2 reduces E-cadherin levels at junctions. TRIP10 binds to and requires VAV2 function for its junctional localization. Overall, we present new conceptual insights on junction stabilization, which integrate known and novel pathways with impact for epithelial morphogenesis, homeostasis and diseases. 1 National Heart and Lung Institute, Faculty of Medicine, Imperial College London, London SW7 2AZ, UK. 2 Computing Department, Imperial College London, London SW7 2AZ, UK. 3 Bioengineering Department, Faculty of Engineering, Imperial College London, London SW7 2AZ, UK. 4 Department of Surgery & Cancer, Faculty of Medicine, Imperial College London, London SW7 2AZ, UK.
  • A Computational Approach for Defining a Signature of Β-Cell Golgi Stress in Diabetes Mellitus

    A Computational Approach for Defining a Signature of Β-Cell Golgi Stress in Diabetes Mellitus

    Page 1 of 781 Diabetes A Computational Approach for Defining a Signature of β-Cell Golgi Stress in Diabetes Mellitus Robert N. Bone1,6,7, Olufunmilola Oyebamiji2, Sayali Talware2, Sharmila Selvaraj2, Preethi Krishnan3,6, Farooq Syed1,6,7, Huanmei Wu2, Carmella Evans-Molina 1,3,4,5,6,7,8* Departments of 1Pediatrics, 3Medicine, 4Anatomy, Cell Biology & Physiology, 5Biochemistry & Molecular Biology, the 6Center for Diabetes & Metabolic Diseases, and the 7Herman B. Wells Center for Pediatric Research, Indiana University School of Medicine, Indianapolis, IN 46202; 2Department of BioHealth Informatics, Indiana University-Purdue University Indianapolis, Indianapolis, IN, 46202; 8Roudebush VA Medical Center, Indianapolis, IN 46202. *Corresponding Author(s): Carmella Evans-Molina, MD, PhD ([email protected]) Indiana University School of Medicine, 635 Barnhill Drive, MS 2031A, Indianapolis, IN 46202, Telephone: (317) 274-4145, Fax (317) 274-4107 Running Title: Golgi Stress Response in Diabetes Word Count: 4358 Number of Figures: 6 Keywords: Golgi apparatus stress, Islets, β cell, Type 1 diabetes, Type 2 diabetes 1 Diabetes Publish Ahead of Print, published online August 20, 2020 Diabetes Page 2 of 781 ABSTRACT The Golgi apparatus (GA) is an important site of insulin processing and granule maturation, but whether GA organelle dysfunction and GA stress are present in the diabetic β-cell has not been tested. We utilized an informatics-based approach to develop a transcriptional signature of β-cell GA stress using existing RNA sequencing and microarray datasets generated using human islets from donors with diabetes and islets where type 1(T1D) and type 2 diabetes (T2D) had been modeled ex vivo. To narrow our results to GA-specific genes, we applied a filter set of 1,030 genes accepted as GA associated.
  • Protein Identities in Evs Isolated from U87-MG GBM Cells As Determined by NG LC-MS/MS

    Protein Identities in Evs Isolated from U87-MG GBM Cells As Determined by NG LC-MS/MS

    Protein identities in EVs isolated from U87-MG GBM cells as determined by NG LC-MS/MS. No. Accession Description Σ Coverage Σ# Proteins Σ# Unique Peptides Σ# Peptides Σ# PSMs # AAs MW [kDa] calc. pI 1 A8MS94 Putative golgin subfamily A member 2-like protein 5 OS=Homo sapiens PE=5 SV=2 - [GG2L5_HUMAN] 100 1 1 7 88 110 12,03704523 5,681152344 2 P60660 Myosin light polypeptide 6 OS=Homo sapiens GN=MYL6 PE=1 SV=2 - [MYL6_HUMAN] 100 3 5 17 173 151 16,91913397 4,652832031 3 Q6ZYL4 General transcription factor IIH subunit 5 OS=Homo sapiens GN=GTF2H5 PE=1 SV=1 - [TF2H5_HUMAN] 98,59 1 1 4 13 71 8,048185945 4,652832031 4 P60709 Actin, cytoplasmic 1 OS=Homo sapiens GN=ACTB PE=1 SV=1 - [ACTB_HUMAN] 97,6 5 5 35 917 375 41,70973209 5,478027344 5 P13489 Ribonuclease inhibitor OS=Homo sapiens GN=RNH1 PE=1 SV=2 - [RINI_HUMAN] 96,75 1 12 37 173 461 49,94108966 4,817871094 6 P09382 Galectin-1 OS=Homo sapiens GN=LGALS1 PE=1 SV=2 - [LEG1_HUMAN] 96,3 1 7 14 283 135 14,70620005 5,503417969 7 P60174 Triosephosphate isomerase OS=Homo sapiens GN=TPI1 PE=1 SV=3 - [TPIS_HUMAN] 95,1 3 16 25 375 286 30,77169764 5,922363281 8 P04406 Glyceraldehyde-3-phosphate dehydrogenase OS=Homo sapiens GN=GAPDH PE=1 SV=3 - [G3P_HUMAN] 94,63 2 13 31 509 335 36,03039959 8,455566406 9 Q15185 Prostaglandin E synthase 3 OS=Homo sapiens GN=PTGES3 PE=1 SV=1 - [TEBP_HUMAN] 93,13 1 5 12 74 160 18,68541938 4,538574219 10 P09417 Dihydropteridine reductase OS=Homo sapiens GN=QDPR PE=1 SV=2 - [DHPR_HUMAN] 93,03 1 1 17 69 244 25,77302971 7,371582031 11 P01911 HLA class II histocompatibility antigen,