HARVARD
MEDICAL
SCHOOL
Robust Radiomics Methods
Hugo Aerts
Director, Computational Imaging and Bioinformatics Lab (CIBL)
Dana-Farber Cancer Institute, Brigham and Women’s Hospital
Harvard Medical School
Objectives
- Describe the motivation for integrating imaging with genomic
and clinical data
- Describe robust methodology underlying quantitative radiomic
analysis
- Describe biomarker quantification studies in Radiomics and
Imaging-Genomics (Radiogenomics)
Imaging for personalized medicine
Advantages of Imaging:
- Performed non-invasively
- Covers the total 3D volume
- Already performed in clinical practice
- Multiple times during treatment for diagnosis, staging, radiation oncology
planning, response assessment
Disadvantages of Imaging:
- Probes the cancer at the macroscopic level
- Often qualitative not quantitative
- Very heterogeneous acquisition protocols:
- comparisons between patients difficult
- comparisons same patient in time difficult
- Storage of only reconstructed images (not the raw data)
1
Representative CT images of lung cancer
Tumors are different
Medical imaging can capture these phenotypic differences
Integrating Imaging and Genomic Data
Radiomic Data
Clinical Data
Genomic Data
Imaging-Genomics
Radiomics
Imaging
Radiomics Data
Feature
extraction
Clinical Data
Metabolome
Biologic Data
Proteome
Transcriptome
Genome
Integrating Tissue Imaging data with the underlying Biology
2
Radiomics rational
- Radiographic images are typically analysed qualitatively by radiologist,
often with non-standard lexicon.
- At most, unidirectional measurements (RECIST)
- Radiomics aims to provide a comprehensive quantification of the tumor
phenotype using automated image characterisation algorithms
- We hypothesize that radiomic analyses of standard of care images can
improve diagnostic, prognostic and predictive power
- Automation is key: automatic quantitative feature algorithms to extract
quantitative data instead of qualitative data, reduce observer variation by
manual annotation, and increase speed of workflow.
Radiomics: Quantify the tumor phenotype
Convert Images to mineable data in high throughput (radiomics)
Area=1201.6 mm 2
Perimeter=152.4 mm
Volume=2615 mm 3
Surf. area=1099.33 mm 2
Surf. Area/volume=0.42 mm -1
Density, Necrosis
Mean = 19.33 HU
SD = 76.59 HU
Min = -249 HU
Max = 118 HU
Spiculations
Slope at margin =133.5±31.3 HU/mm
Low density inclusions
Rel. vol.= 0.21 mm 3
Number=110
Volume=4.89±8.35 mm 3
*Lambin et al.Eur J Cancer 2012
PAGE 8
*Kumar et al. Magn Reson Imaging
2012
Radiomics: Workflow & Challenges
Image Acquisition, Reconstruction, Standardization, Storage
PAGE 9
3
Radiomics: Workflow & Challenges
Image Acquisition, reconstruction, standardization, storage
Automate, Validate, Reproducibility
Automatic segmentation:
1) Automated method for high throughput of images.
2) Reducing the high intra- and inter-observer
variability observed for target definition.
PAGE
10
Automatic tumor delineation using 3D-Slicer
Developing algorithms for fast, semi-automated, and accurate delineation
Automatic tumor delineation using 3D-Slicer
*Velazquez et al, Sci Rep. 2013
4
Manual
3D-Slicer
3D-Slicer region growing algorithm
*Velazquez et al, Sci Rep. 2013
Manual
Uncertainty Region
3D-Slicer
Uncertainty Region
Segmentation uncertainty was significantly smaller with 3D-Slicer (Velazquez et al, Sci Rep. 2013)
Radiomics features based on 3D-Slicer delineations are more stable (Parmar et al. PLOS One 2014)
Radiomics: Workflow & Challenges
Image Acquisition, reconstruction, standardization, storage
Automate, Validate, Reproducibility
Area=1201.6 mm 2
Perimeter=152.4 mm
Volume=2615 mm 3
Surf. area=1099.33 mm 2
Surf. Area/volume=0.42 mm -1
Density, Necrosis
Mean = 19.33 HU
SD = 76.59 HU
Min = -249 HU
Max = 118 HU
Spiculations
Slope at margin =133.5±31.3 HU/mm
Low density inclusions
Rel. vol.= 0.21 mm 3
Number=110
Volume=4.89±8.35 mm 3
Definition, Informative, Reproducibility,
Robustness
PAGE
15
5
Radiomic Feature Set (current release ~1600 features)
RLGL
GCLM
GLSZM
GLCM
GLRL
Wavelet
Texture
LoG
Shape
RLGL
Texture
GCLM
Stats
GLSZM
Texture
GCLM
Stats
GLSZM
RLGL
Stats
Kurtosis:
Entropy:
Radiomic features can capture tumor phenotypic details
HARVARD
MEDICAL
SCHOOL
Robust Radiomics Data Analysis
(Feature Selection & Machine learning)
Motivation
•
Predictive/Prognostic models having high accuracy, reliability and efficiency
can be vital factors driving success of “Radiomics”.
•
Need for the machine-learning models.
•
Radiomics suffers from the curse of dimensionality.
•
Need for the feature selection.
•
Different feature selection and machine-learning classification methods
have to be investigated.
6
HARVARD
Radiomics Dimensionality Reduction
MEDICAL
SCHOOL
Radiomics Features
Matrix of 440 Radiomics
features
(422 NSCLC patients)
Spearman's rank
correlation coefficient
-1
0
1
Radiomics Features
Feature selection: RIDER test retest
 Rider test retest reproducibility to select the most reproducible tumor image
features extracted from CT images of 31 non-small cell lung cancer (NSCLC) patients.
 CT scans acquired within fifteen minutes.
 All primary lung cancers were segmented using Definiens
 440 radiomics features were extracted from these segmented tumor regions
 Intraclass Correlation Coefficient (ICC) was calculated for each feature as a stability
index
Scan 1
Scan 2
[ Lung CT image with segmented tumor region shown with green outline]
Robust Machine Learning in Radiomics
*Parmar et al. submitted
7
0.64
0.61
0.61
0.68
0.65
0.64
0.64
0.6
0.5
0.55
0.64
0.51
0.65
0.66
0.63
0.67
0.6
0.63
0.61
0.63
0.52
0.68
0.68
0.65
0.69
0.59
0.59
0.61
0.63
0.62
0.64
0.61
0.61
0.61
0.61
0.62
0.61
0.62
0.64
0.64
0.67
0.56
0.64
0.57
0.62
0.57
0.67
0.65
0.67
0.68
0.64
0.61
0.54
0.59
0.56
0.54
0.62
0.6
0.61
0.64
0.59
0.57
0.66
0.67
0.62
0.59
0.64
0.66
0.53
0.59
0.54
0.53
0.6
0.61
0.59
0.54
0.67
0.56
0.56
0.64
0.63
0.6
0.64
0.65
0.53
0.53
0.59
0.58
0.61
0.58
0.61
0.63
0.62
0.63
0.62
0.66
0.53
0.53
0.61
0.61
0.61
0.62
0.62
0.62
0.61
0.61
0.64
0.66
0.53
0.53
0.53
0.53
DT
40
BY
BST
20
RF
BAG
Count
MARS
0
DA
FSCR
0.58
0.53
0.53
0.66
0.62
0.63
0.62
0.63
0.61
0.62
0.64
0.64
GINI
0.57
0.53
0.53
0.65
0.64
0.6
0.61
0.58
0.6
0.6
0.62
0.63
CHSQ
0.55
0.56
0.56
0.64
0.63
0.67
0.54
0.59
0.61
0.63
0.6
0.63
JMI
0.55
0.54
0.59
0.64
0.59
0.66
0.57
0.61
0.6
0.61
0.62
0.6
CIFE
0.51
0.53
0.53
0.66
0.62
0.67
0.59
0.64
0.62
0.61
0.63
0.64
DISR
0.55
0.54
0.54
0.61
0.67
0.65
0.62
0.57
0.61
0.61
0.61
0.59
MIM
0.58
0.56
0.59
0.64
0.68
0.67
0.57
0.64
0.61
0.63
0.61
0.62
CMIM
0.57
0.61
0.62
0.64
0.64
0.67
0.56
0.62
0.59
0.6
0.61
0.61
ICAP
0.6
0.61
0.61
0.64
0.62
0.63
0.61
0.59
0.61
0.6
0.64
0.63
TSCR
0.53
0.55
0.63
0.52
0.68
0.68
0.65
0.69
0.6
0.6
0.63
0.62
MRMR
0.56
0.5
0.6
0.51
0.65
0.66
0.63
0.67
0.63
0.61
0.63
0.65
MIFS
0.67
0.64
0.64
0.64
0.65
0.68
0.61
0.61
0.64
0.67
0.65
0.66
WLCX
0
20
40
Nnet
Count
ML Classification Methods
Feature Selection Methods
RELF
0.63
PLSR
0.56
0.53
0.63
0.62
GLM
0.6
0.57
0.65
0.64
NN
0.58
0.64
0.59
DA
0.55
0.58
0.61
SVM
0.51
0.61
0.62
MARS
0.55
0.61
0.62
RF
0.55
0.62
0.61
BAG
0.57
0.61
0.64
BY
0.58
0.66
0.53
DT
0.61
0.53
0.53
Value
0.6
0.5
0.53
0.61
BST
Color Key
and Histogram
0.61
Machine Learning in Radiomics
0.61
0.67
0.6
Value
Nnet
0.5
SVM
Color Key
and Histogram
*Parmar et al. submitted
Stability for feature selection and Classification
*Parmar et al. submitted
Machine Learning in Radiomics
20
10
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*Parmar et al. submitted
8
Imaging-Genomics across cancer types
I) CT Imaging
II) Feature Extrac on
III) Analysis
Radiomic Features
Gene expression
*Aerts et al. Nature Comm. 2014
Tumor Intensity
Tumor Shape
Clinical Data
Tumor Texture
Wavelet
• Radiomics analysis on CT imaging of >1000 patients with Lung or
H&N cancer
• Developed and validated a prognostic radiomics signature that
can be applied across cancer types
• Imaging-Genomics analysis showed strong correlations between
radiomics and genomics data
-2
-1
0
z-score
1
Lung1 Dataset
422 NSCLC Patients MAASTRO Clinic
2
Patients
Intensity
Radiomics Features
Shape
Texture
HHH
HHL
HLL
LHH
Wavelet
HLH
LHL
LLH
LLL
Clusters
I
II
III
T-stage
1 2 3 4 5
N-stage
0 1 2 3 4
M-stage
0 >1
Overall Stage
I
II
IIIA IIIB IV
Histology
adenocarcinoma
squamous cell carcinoma
large cell carcinoma
not otherwise speci ed (nos)
NA
Radiomics CT Workflow
Radiomics Signature:
1 “Statistics Energy”
2 “ShapeCompactness”
3 “Gray Level Nonuniformity”
4 Wavelet “Gray Level Nonuniformity HLH”
7 datasets with a total of 1018 patients
9
Radiomics CT Signature Performance
Head & neck cancer cohorts
Survival Probability
Lung cancer cohorts
Survival time (days)
Survival time (days)
Performance Model:
- CI = 0.65 on the Lung2 Validation Dataset (n=225)
Performance Model:
- CI = 0.69 on Maastro H&N dataset (n=136)
- CI = 0.69 on VU H&N dataset (n=95)
*Aerts et al. Nature Comm. 2014
Radiomics CT Signature Performance
-
Signature performed significantly better compared to volume in all datasets.
Signature performance was better than TNM staging in Lung2 and H&N2, and
comparable in the H&N1 dataset.
Combining the signature with TNM showed significant improvement in all datasets.
Additional Validation of Prognostic Signature
542 Oropharyngeal squamous cell carcinoma (OPSCC) treated at Princess Margaret
Hospital (PMH) in Toronto.
a
1.0
Kaplan-Meier Radiomics Signature
0.8
<= Median
> Median
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0.2
Survival probability
1.0
0.4
0.6
0.8
*
*
***
**
***
0.2
Survival probability
b
Kaplan-Meier Radiomic Signature
*
0
500
1000
1500
Survival time (days)
MAASTRO (n=136)
VUmc (n=95)
0.0
0.0
PMH: all (n=542)
PMH: no CT artifacts (n=267)
PMH: artifacts (n=275)
2000
2500
0
500
1000
1500
2000
Survival time (days)
C-index was: PMH1: 0.628 (P<2.72e-9), PMH2: 0.634 (P<2.7e-6) and PMH3: 0.647 (P<5.35e-6)
Radiomics signature could be validated in an additional large OPSCC cohort
*Leijnaar et al. Acta Onco 2015
10
GSEA of Prognostic Radiomics Signature
Dataset of 89 Stage I NSCLC patients treated with surgery
Radiomics-Genomics in NSCLC
I) Medical Image
(B)
D1
D2
R+G
n=262
Enrichment
analysis
Radiomic feature
Pathway
II) Segmentation
Correlation to pathway activity
III) 3D mask
Independent
validations
R+G
n=89
Identification of modules
Radiomic feature
IV) Feature extraction
Pathway
Association to
clinical data
R+G+C
n=224
V) Data integration
Clinical characterization of module
s
Independent
validations
R+G+C
n=87
Meta-analysis
*Grossmann et al. Submitted
Color Key
Stats
Shape
LoG_sigma
Wavelet
RLGL
GLSZM
GLCM
Association Heatmap Radiomics-Genomics
−1
0
1
2
Value
TRNA_AMINOACYLATION
MITOCHONDRIAL_TRNA_AMINO ACYLATION
CYTOSOLIC_TRNA_AMINO ACYLATION
DOUBLE_STRAND_BREAK_REP AIR
PROCESSIVE_SYNTHESIS_ON_THE_LA GGING_STRAND
HOMOLOGOUS_RECOMBINATION_REPAIR_OF_REPLICATION_INDEPENDENT_DOUBLE_STRAND_BREAKS
FANCONI_ANEMIA_PATHWAY
RECRUITMENT_OF_MITOTIC_CENTROSOME_PROTEINS_AND_COMPLEXES
LOSS_OF_NLP_FR OM_MITOTIC_CENTROSOMES
MITOTIC_G2_G2_M_PHASES
KINESINS
PROTEIN_FOLDING
GLUCOSE_METABOLISM
GLYCOLYSIS
ACETYLCHOLINE_BINDING_AND_DO WNSTREAM_EVENTS
PREFOLDIN_MEDIATED_TRANSFER_OF_SUBSTRA TE_TO_CCT_TRIC
FORMATION_OF_TUBULIN_FOLDING_INTERMEDIA TES_BY_CCT_TRIC
SIGNALLING_TO_P38_VIA_RIT_AND_RIN
PROLONGED_ERK_A CTIVATION_EVENTS
SHC1_EVENTS_IN_EGFR_SIGNALING
PROCESSING_OF_CAPPED_INTR ONLESS_PRE_MRNA
AMINO_ACID_SYNTHESIS_AND_INTERCONVERSION_TRANSAMINA TION
GLUCONEOGENESIS
DESTABILIZATION_OF_MRNA_BY_KSRP
MICRORNA_MIRNA_BIOGENESIS
REGULATORY_RNA_PATHWAYS
INFLUENZA_LIFE_CYCLE
INFLUENZA_VIRAL_RNA_TRANSCRIPTION_AND_REPLICA TION
3_UTR_MEDIATED_TRANSLATIONAL_REGULATION
TRANSLATION
SRP_DEPENDENT_CO TRANSLATIONAL_PROTEIN_TARGETING_TO_MEMBRANE
PEPTIDE_CHAIN_ELONGA TION
NONSENSE_MEDIATED_DECAY_ENHANCED_BY_THE_EXON_JUNCTION_COMPLEX
ACTIVATION_OF_THE_MRNA_UPON_BINDING_OF_THE_CAP_BINDING_COMPLEX_AND_EIFS_AND_SUBSEQ UENT_BINDING_TO_43S
FORMATION_OF_THE_TERNAR Y_COMPLEX_AND_SUBSEQ UENTLY_THE_43S_COMPLEX
METABOLISM_OF_RNA
METABOLISM_OF_MRNA
ABORTIVE_ELONGATION_OF_HIV1_TRANSCRIPT_IN_THE_ABSENCE_OF_T AT
MITOCHONDRIAL_PR OTEIN_IMPORT
BASE_EXCISION_REPAIR
RESOLUTION_OF_AP_SITES_VIA_THE_MUL TIPLE_NUCLEO TIDE_PATCH_REPLACEMENT_PATHWAY
POST_CHAPER ONIN_TUBULIN_FOLDING_PATHWAY
RESPIRATORY_ELECTRON_TRANSPORT
RESPIRATORY_ELECTRON_TRANSPORT_ATP_SYNTHESIS_BY_CHEMIOSMO TIC_COUPLING_AND_HEA T_PRODUCTION_BY_UNCOUPLING_PR OTEINS_
TCA_CYCLE_AND_RESPIRA TORY_ELECTRON_TRANSPORT
RNA_POL_III_TRANSCRIPTION_TERMINA TION
RNA_POL_III_CHAIN_ELONGA TION
RNA_POL_III_TRANSCRIPTION_INITIA TION_FROM_TYPE_3_PROMOTER
RNA_POL_III_TRANSCRIPTION_INITIA TION_FROM_TYPE_2_PROMOTER
RNA_POL_III_TRANSCRIPTION
PROCESSING_OF_CAPPED_INTR ON_CONTAINING_PRE_MRNA
MRNA_SPLICING
MRNA_PROCESSING
MRNA_SPLICING_MINOR_PATHWAY
TRANSCRIPTION_COUPLED_NER_TC_NER
NUCLEOTIDE_EXCISION_REPAIR
FORMATION_OF_THE_HIV1_EARLY_ELONGATION_COMPLEX
GLOBAL_GENOMIC_NER_GG_NER
TRANSPORT_OF_MATURE_TRANSCRIPT_T O_CYTOPLASM
CLEAVAGE_OF_GROWING_TRANSCRIPT_IN_THE_TERMINA TION_REGION_
MRNA_3_END_PR OCESSING
G2_M_CHECKPOINTS
ACTIVATION_OF_ATR_IN_RESPONSE_T O_REPLICATION_STRESS
ACTIVATION_OF_THE_PRE_REPLICA TIVE_COMPLEX
EXTENSION_OF_TELOMERES
LAGGING_STRAND_SYNTHESIS
DNA_STRAND_ELONGATION
DNA_REPAIR
CYCLIN_A_B1_ASSOCIA TED_EVENTS_DURING_G2_M_TRANSITION
G1_S_SPECIFIC_TRANSCRIPTION
E2F_MEDIATED_REGULATION_OF_DNA_REPLICATION
MEIOTIC_SYNAPSIS
AMYLOIDS
RNA_POL_I_PR OMOTER_OPENING
PACKAGING_OF_TELOMERE_ENDS
RNA_POL_I_TRANSCRIPTION
DEPOSITION_OF_NEW_CENP A_CONTAINING_NUCLEOSOMES_AT_THE_CENTR OMERE
RNA_POL_I_RNA_POL_III_AND_MIT OCHONDRIAL_TRANSCRIPTION
TRANSCRIPTION
TELOMERE_MAINTENANCE
MEIOTIC_RECOMBINATION
MEIOSIS
CHROMOSOME_MAINTENANCE
DNA_REPLICATION
MITOTIC_M_M_G1_PHASES
MITOTIC_PROMETAPHASE
CELL_CYCLE_MIT OTIC
CELL_CYCLE
CELL_CYCLE_CHECKPOINTS
G1_S_TRANSITION
S_PHASE
SYNTHESIS_OF_DNA
METABOLISM_OF_NUCLEO TIDES
METABOLISM_OF_CARBOHYDRA TES
CHONDROITIN_SULFATE_BIOSYNTHESIS
SYNTHESIS_AND_INTERCONVERSION_OF_NUCLEO TIDE_DI_AND_TRIPHOSPHA TES
GLYCOSAMINOGLYCAN_METABOLISM
HS_GAG_BIOSYNTHESIS
DIABETES_PATHWAYS
KERATAN_SULFATE_KERATIN_METABOLISM
KERATAN_SULFATE_BIOSYNTHESIS
ACTIVATED_TAK1_MEDIATES_P38_MAPK_A CTIVATION
JNK_C_JUN_KINASES_PHOSPHOR YLATION_AND_ACTIVATION_MEDIATED_BY_ACTIVATED_HUMAN_TAK1
ARMS_MEDIATED_ACTIVATION
IL1_SIGNALING
METABOLISM_OF_AMINO_A CIDS_AND_DERIVATIVES
APOPTOSIS
NCAM_SIGNALING_FOR_NEURITE_OUT_GR OWTH
ACTIVATION_OF_CHAPER ONE_GENES_BY_XBP1S
YAP1_AND_WWTR1_TAZ_STIMULATED_GENE_EXPRESSION
GAP_JUNCTION_ASSEMBLY
GAP_JUNCTION_TRAFFICKING
HEPARAN_SULFATE_HEPARIN_HS_GAG_METABOLISM
CHONDROITIN_SULFATE_DERMATAN_SULFATE_METABOLISM
A_TETRASACCHARIDE_LINKER_SEQ UENCE_IS_REQ UIRED_FOR_GAG_SYNTHESIS
COLLAGEN_FORMATION
EXTRACELLULAR_MATRIX_ORGANIZATION
ASSOCIATION_OF_TRIC_CCT_WITH_T ARGET_PROTEINS_DURING_BIOSYNTHESIS
METABOLISM_OF_PROTEINS
UNFOLDED_PR OTEIN_RESPONSE
PERK_REGULATED_GENE_EXPRESSION
ACTIVATION_OF_GENES_BY_ATF4
PYRUVATE_METABOLISM
G1_PHASE
PYRIMIDINE_METABOLISM
INTRINSIC_PATHWAY_FOR_APOPTOSIS
ACTIVATION_OF_BH3_ONLY_PROTEINS
RNA_POL_II_TRANSCRIPTION_PRE_INITIA TION_AND_PROMOTER_OPENING
RNA_POL_II_TRANSCRIPTION
RNA_POL_II_PRE_TRANSCRIPTION_EVENTS
MRNA_CAPPING
HIV_LIFE_CYCLE
LATE_PHASE_OF_HIV_LIFE_CYCLE
TRANSPORT_OF_RIBONUCLEOPR OTEINS_INTO_THE_HOST_NUCLEUS
GLUCOSE_TRANSPOR T
TRANSPORT_OF_MATURE_MRNA_DERIVED_FR OM_AN_INTRONLESS_TRANSCRIPT
METABOLISM_OF_NON_CODING_RNA
NEP_NS2_INTERA CTS_WITH_THE_CELLULAR_EXPOR T_MACHINERY
INTERACTIONS_OF_VPR_WITH_HOST_CELLULAR_PR OTEINS
REGULATION_OF_GLUCOKINASE_BY_GLUCOKINASE_REGULA TORY_PROTEIN
APC_CDC20_MEDIATED_DEGRADATION_OF_NEK2A
INHIBITION_OF_THE_PR OTEOLYTIC_ACTIVITY_OF_APC_C_REQ UIRED_FOR_THE_ONSET_OF_ANAPHASE_BY_MIT OTIC_SPINDLE_CHECKPOINT_COMPONENTS
APC_C_CDC20_MEDIATED_DEGRADATION_OF_CYCLIN_B
PHOSPHORYLATION_OF_THE_APC_C
CONVERSION_FR OM_APC_C_CDC20_T O_APC_C_CDH1_IN_LATE_ANAPHASE
ASSEMBLY_OF_THE_PRE_REPLICA TIVE_COMPLEX
ORC1_REMOVAL_FROM_CHROMATIN
REGULATION_OF_MITOTIC_CELL_CYCLE
MITOTIC_G1_G1_S_PHASES
M_G1_TRANSITION
APC_C_CDH1_MEDIATED_DEGRADATION_OF_CDC20_AND_O THER_APC_C_CDH1_TARGETED_PR OTEINS_IN_LATE_MITOSIS_EARLY_G1
APC_C_CDC20_MEDIATED_DEGRADATION_OF_MITOTIC_PROTEINS
HIV_INFECTION
G0_AND_EARLY_G1
FACTORS_INVOLVED_IN_MEGAKAR YOCYTE_DEVELOPMENT_AND_PLA TELET_PRODUCTION
P53_INDEPENDENT_G1_S_DNA_D AMAGE_CHECKPOINT
SCF_BETA_TRCP_MEDIATED_DEGRADATION_OF_EMI1
CDT1_ASSOCIATION_WITH_THE_CDC6_ORC_ORIGIN_COMPLEX
AUTODEGRADATION_OF_CDH1_BY_CDH1_APC_C
CYCLIN_E_ASSOCIATED_EVENTS_DURING_G1_S_TRANSITION_
SCFSKP2_MEDIATED_DEGRADATION_OF_P27_P21
CDK_MEDIATED_PHOSPHORYLATION_AND_REMO VAL_OF_CDC6
P53_DEPENDENT_G1_DNA_D AMAGE_RESPONSE
DESTABILIZATION_OF_MRNA_BY_A UF1_HNRNP_D0
HOST_INTERACTIONS_OF_HIV_FACTORS
REGULATION_OF_MRNA_STABILITY_BY_PR OTEINS_THAT_BIND_AU_RICH_ELEMENTS
MHC_CLASS_II_ANTIGEN_PRESENT ATION
PURINE_METABOLISM
OLFACTORY_SIGNALING_PATHWAY
ANTIVIRAL_MECHANISM_BY_IFN_STIMULA TED_GENES
ANTIGEN_PROCESSING_UBIQ UITINATION_PROTEASOME_DEGRADATION
REGULATION_OF_ORNITHINE_DECARBO XYLASE_ODC
AUTODEGRADATION_OF_THE_E3_UBIQ UITIN_LIGASE_COP1
VIF_MEDIATED_DEGRADATION_OF_APOBEC3G
ER_PHAGOSOME_PATHWAY
ACTIVATION_OF_NF_KAPPAB_IN_B_CELLS
REGULATION_OF_INSULIN_LIKE_GR OWTH_FACTOR_IGF_ACTIVITY_BY_INSULIN_LIKE_GR OWTH_FACTOR_BINDING_PR OTEINS_IGFBPS
N_GLYCAN_ANTENNAE_ELONGA TION_IN_THE_MEDIAL_TRANS_GOLGI
AMINO_ACID_TRANSPOR T_ACROSS_THE_PLASMA_MEMBRANE
FATTY_ACYL_COA_BIOSYNTHESIS
INSULIN_SYNTHESIS_AND_PR OCESSING
AMINE_DERIVED_HORMONES
SIGNALING_BY_HIPPO
NOD1_2_SIGNALING_PATHWAY
BASIGIN_INTERA CTIONS
SIGNALING_BY_SCF_KIT
PPARA_ACTIVATES_GENE_EXPRESSION
POST_TRANSLATIONAL_PROTEIN_MODIFICATION
ASPARAGINE_N_LINKED_GLYCOSYLATION
CROSS_PRESENTATION_OF_SOLUBLE_EXOGENOUS_ANTIGENS_ENDOSOMES
ANTIGEN_PROCESSING_CR OSS_PRESENTATION
DOWNSTREAM_SIGNALING_EVENTS_OF_B_CELL_RECEPT OR_BCR
SIGNALING_BY_WNT
CLASS_I_MHC_MEDIATED_ANTIGEN_PR OCESSING_PRESENTATION
REGULATION_OF_APOPTOSIS
ACTIVATION_OF_KAINATE_RECEPTORS_UPON_GLUTAMATE_BINDING
G_BETA_GAMMA_SIGNALLING_THR OUGH_PLC_BETA
PRE_NOTCH_TRANSCRIPTION_AND_TRANSLA TION
PRE_NOTCH_EXPRESSION_AND_PR OCESSING
NEF_MEDIATES_DOWN_MODULATION_OF_CELL_SURFACE_RECEPTORS_BY_RECRUITING_THEM_T O_CLATHRIN_ADAPTERS
NCAM1_INTERACTIONS
HS_GAG_DEGRADATION
SMOOTH_MUSCLE_CONTRA CTION
ADHERENS_JUNCTIONS_INTERA CTIONS
MEMBRANE_TRAFFICKING
DEGRADATION_OF_THE_EXTRA CELLULAR_MATRIX
GLUTATHIONE_CONJUGATION
SEMA4D_INDUCED_CELL_MIGRA TION_AND_GROWTH_CONE_COLLAPSE
METABOLISM_OF_VITAMINS_AND_COFACTORS
METABOLISM_OF_POLYAMINES
SIGNALING_BY_CONSTITUTIVEL Y_ACTIVE_EGFR
SIGNALING_BY_ROBO_RECEPTOR
SIGNALLING_TO_ERKS
SIGNALLING_TO_RAS
ENDOSOMAL_SORTING_COMPLEX_REQ UIRED_FOR_TRANSPOR T_ESCRT
CHOLESTEROL_BIOSYNTHESIS
ELONGATION_ARREST_AND_RECO VERY
SHC_RELATED_EVENTS
SHC_MEDIATED_SIGNALLING
SHC1_EVENTS_IN_ERBB4_SIGNALING
GRB2_EVENTS_IN_ERBB2_SIGNALING
BMAL1_CLOCK_NPAS2_ACTIVATES_CIRCADIAN_EXPRESSION
CIRCADIAN_CLOCK
NOTCH1_INTRACELLULAR_DOMAIN_REGULA TES_TRANSCRIPTION
CIRCADIAN_REPRESSION_OF_EXPRESSION_BY_REV_ERBA
RORA_ACTIVATES_CIRCADIAN_EXPRESSION
DESTABILIZATION_OF_MRNA_BY_BRF1
DESTABILIZATION_OF_MRNA_BY_TRISTETRAPR OLIN_TTP
DEADENYLATION_DEPENDENT_MRNA_DECA Y
APOPTOTIC_EXECUTION_PHASE
SMAD2_SMAD3_SMAD4_HETER OTRIMER_REGULATES_TRANSCRIPTION
DEADENYLATION_OF_MRNA
CITRIC_ACID_CYCLE_TCA_CYCLE
REGULATION_OF_HYPOXIA_INDUCIBLE_FACTOR_HIF_BY_OXYGEN
PYRUVATE_METABOLISM_AND_CITRIC_A CID_TCA_CYCLE
POST_TRANSLATIONAL_MODIFICATION_SYNTHESIS_OF_GPI_ANCHORED_PR OTEINS
SYNTHESIS_OF_GLYCOSYLPHOSPHATIDYLINOSITOL_GPI
BIOSYNTHESIS_OF_THE_N_GLYCAN_PRECURSOR_DOLICHOL_LIPID_LINKED_OLIGOSA CCHARIDE_LLO_AND_TRANSFER_T O_A_NASCENT_PR OTEIN
PKB_MEDIATED_EVENTS
FORMATION_OF_RNA_POL_II_ELONGA TION_COMPLEX_
FORMATION_OF_TRANSCRIPTION_COUPLED_NER_TC_NER_REP AIR_COMPLEX
RNA_POL_I_TRANSCRIPTION_TERMINA TION
SPHINGOLIPID_DE_NO VO_BIOSYNTHESIS
ZINC_TRANSPOR TERS
O_LINKED_GLYCOSYLATION_OF_MUCINS
GLYCOGEN_BREAKDO WN_GLYCOGENOLYSIS
SIGNALING_BY_TGF_BETA_RECEPTOR_COMPLEX
DOWNREGULATION_OF_TGF_BETA_RECEPTOR_SIGNALING
TGF_BETA_RECEPTOR_SIGNALING_A CTIVATES_SMADS
SIGNALING_BY_ERBB4
TRANSCRIPTIONAL_A CTIVITY_OF_SMAD2_SMAD3_SMAD4_HETER OTRIMER
FRS2_MEDIATED_CASCADE
SHC_MEDIATED_CASCADE
SIGNALING_BY_FGFR_MUTANTS
INSULIN_RECEPT OR_SIGNALLING_CASCADE
SIGNALING_BY_INSULIN_RECEPT OR
PIP3_ACTIVATES_AKT_SIGNALING
PI3K_AKT_ACTIVATION
OXYGEN_DEPENDENT_PR OLINE_HYDROXYLATION_OF_HYPOXIA_INDUCIBLE_FACTOR_ALPHA
SULFUR_AMINO_A CID_METABOLISM
RNA_POL_I_TRANSCRIPTION_INITIA TION
THROMBOXANE_SIGNALLING_THR OUGH_TP_RECEPT OR
SIGNAL_AMPLIFICATION
ADP_SIGNALLING_THR OUGH_P2RY1
GASTRIN_CREB_SIGNALLING_P ATHWAY_VIA_PKC_AND_MAPK
G_ALPHA_Q_SIGNALLING_EVENTS
THROMBIN_SIGNALLING_THR OUGH_PROTEINASE_ACTIVATED_RECEPTORS_PARS
G_BETA_GAMMA_SIGNALLING_THR OUGH_PI3KGAMMA
CLASS_B_2_SECRETIN_F AMILY_RECEPTORS
GLUCAGON_TYPE_LIGAND_RECEPT ORS
G_ALPHA1213_SIGNALLING_EVENTS
SIGNALLING_BY_NGF
SIGNALING_BY_EGFR_IN_CANCER
DOWNSTREAM_SIGNAL_TRANSDUCTION
PI3K_CASCADE
NEGATIVE_REGULATION_OF_FGFR_SIGNALING
NGF_SIGNALLING_VIA_TRKA_FR OM_THE_PLASMA_MEMBRANE
SIGNALING_BY_FGFR_IN_DISEASE
SIGNALING_BY_FGFR
DOWNSTREAM_SIGNALING_OF_A CTIVATED_FGFR
PI_3K_CASCADE
PROSTACYCLIN_SIGNALLING_THR OUGH_PROSTACYCLIN_RECEPT OR
INHIBITION_OF_INSULIN_SECRETION_BY_ADRENALINE_NORADRENALINE
ADP_SIGNALLING_THR OUGH_P2RY12
G_PROTEIN_ACTIVATION
G_PROTEIN_BETA_GAMMA_SIGNALLING
INWARDLY_RECTIFYING_K_CHANNELS
INHIBITION_OF_VOLTAGE_GATED_CA2_CHANNELS_VIA_GBET A_GAMMA_SUBUNITS
HDL_MEDIATED_LIPID_TRANSPOR T
P75_NTR_RECEPT OR_MEDIATED_SIGNALLING
CELL_DEATH_SIGNALLING_VIA_NRA GE_NRIF_AND_NADE
NRAGE_SIGNALS_DEATH_THROUGH_JNK
SIGNALING_BY_NO TCH
REGULATION_OF_BETA_CELL_DEVELOPMENT
TIE2_SIGNALING
EGFR_DOWNREGULATION
SIGNAL_TRANSDUCTION_BY_L1
SIGNALING_BY_NO TCH1
NEPHRIN_INTERA CTIONS
SIGNALING_BY_NOD AL
SIGNALING_BY_ILS
SEMA4D_IN_SEMAPHORIN_SIGNALING
IL_2_SIGNALING
EICOSANOID_LIGAND_BINDING_RECEPT ORS
CD28_CO_STIMULATION
SEMAPHORIN_INTERA CTIONS
GROWTH_HORMONE_RECEPT OR_SIGNALING
AXON_GUIDANCE
SIGNALING_BY_PDGF
DEFENSINS
BETA_DEFENSINS
PROTEOLYTIC_CLEAVAGE_OF_SNARE_COMPLEX_PR OTEINS
BOTULINUM_NEUR OTOXICITY
TRANSPORT_OF_GLUCOSE_AND_O THER_SUGARS_BILE_SAL TS_AND_ORGANIC_A CIDS_METAL_IONS_AND_AMINE_COMPOUNDS
INTERFERON_SIGNALING
CYTOKINE_SIGNALING_IN_IMMUNE_SYSTEM
SIGNALING_BY_THE_B_CELL_RECEPT OR_BCR
THE_ROLE_OF_NEF_IN_HIV1_REPLICA TION_AND_DISEASE_PATHOGENESIS
GPVI_MEDIATED_ACTIVATION_CASCADE
TRAF6_MEDIATED_IRF7_ACTIVATION
TOLL_RECEPTOR_CASCADES
ACTIVATED_TLR4_SIGNALLING
TRAF6_MEDIATED_INDUCTION_OF_NFKB_AND_MAP_KINASES_UPON_TLR7_8_OR_9_A CTIVATION
MYD88_MAL_CASCADE_INITIA TED_ON_PLASMA_MEMBRANE
NFKB_AND_MAP_KINASES_A CTIVATION_MEDIATED_BY_TLR4_SIGNALING_REPER TOIRE
CELL_SURFACE_INTERACTIONS_AT_THE_VASCULAR_WALL
TCR_SIGNALING
DOWNSTREAM_TCR_SIGNALING
IRON_UPTAKE_AND_TRANSPOR T
TRANSPORT_OF_INORGANIC_CATIONS_ANIONS_AND_AMINO_A CIDS_OLIGOPEPTIDES
AMINE_LIGAND_BINDING_RECEPT ORS
CTLA4_INHIBITORY_SIGNALING
ANTIGEN_PRESENTATION_FOLDING_ASSEMBLY_AND_PEPTIDE_LO ADING_OF_CLASS_I_MHC
REGULATION_OF_KIT_SIGNALING
REGULATION_OF_SIGNALING_BY_CBL
LIGAND_GATED_ION_CHANNEL_TRANSPOR T
CREB_PHOSPHORYLATION_THROUGH_THE_ACTIVATION_OF_CAMKII
REGULATION_OF_GENE_EXPRESSION_IN_BET A_CELLS
GABA_SYNTHESIS_RELEASE_REUPT AKE_AND_DEGRAD ATION
SIGNALING_BY_FGFR1_FUSION_MUT ANTS
SIGNALING_BY_FGFR1_MUTANTS
SPHINGOLIPID_METABOLISM
GLYCOSPHINGOLIPID_METABOLISM
ACTIVATED_POINT_MUTANTS_OF_FGFR2
PTM_GAMMA_CARBOXYLATION_HYPUSINE_FORMATION_AND_ARYLSULFATASE_ACTIVATION
NUCLEOTIDE_BINDING_DOMAIN_LEUCINE_RICH_REPEA T_CONTAINING_RECEPTOR_NLR_SIGNALING_PATHWAYS
ENOS_ACTIVATION_AND_REGULATION
METAL_ION_SLC_TRANSPOR TERS
SLC_MEDIATED_TRANSMEMBRANE_TRANSPOR T
AMINO_ACID_AND_OLIGOPEPTIDE_SLC_TRANSPOR TERS
MYOGENESIS
MAP_KINASE_ACTIVATION_IN_TLR_CASCADE
APOPTOTIC_CLEAVAGE_OF_CELLULAR_PR OTEINS
FORMATION_OF_INCISION_COMPLEX_IN_GG_NER
DOWNREGULATION_OF_SMAD2_3_SMAD4_TRANSCRIPTIONAL_A CTIVITY
LATENT_INFECTION_OF_HOMO_SAPIENS_WITH_MYCOBA CTERIUM_TUBERCULOSIS
TRANSFERRIN_ENDOCYT OSIS_AND_RECYCLING
INSULIN_RECEPT OR_RECYCLING
TRANSPORT_TO_THE_GOLGI_AND_SUBSEQ UENT_MODIFICATION
SYNTHESIS_SECRETION_AND_DEA CYLATION_OF_GHRELIN
SYNTHESIS_SECRETION_AND_INA CTIVATION_OF_GLP1
INCRETIN_SYNTHESIS_SECRETION_AND_INA CTIVATION
SIGNALING_BY_BMP
SIGNALING_BY_ERBB2
FATTY_ACID_TRIACYLGLYCEROL_AND_KETONE_BODY_METABOLISM
ERK_MAPK_TARGETS
MAPK_TARGETS_NUCLEAR_EVENTS_MEDIA TED_BY_MAP_KINASES
NUCLEAR_EVENTS_KINASE_AND_TRANSCRIPTION_F ACTOR_ACTIVATION
DEVELOPMENTAL_BIOLOGY
TRANSCRIPTIONAL_REGULA TION_OF_WHITE_ADIPOCYTE_DIFFERENTIA TION
GAB1_SIGNALOSOME
PI3K_EVENTS_IN_ERBB2_SIGNALING
PI3K_EVENTS_IN_ERBB4_SIGNALING
PHASE_II_CONJUGATION
PEROXISOMAL_LIPID_METABOLISM
CTNNB1_PHOSPHOR YLATION_CASCADE
BRANCHED_CHAIN_AMINO_A CID_CATABOLISM
CELL_CELL_COMMUNICATION
CELL_JUNCTION_ORGANIZA TION
TIGHT_JUNCTION_INTERA CTIONS
CELL_CELL_JUNCTION_ORGANIZA TION
GENERIC_TRANSCRIPTION_P ATHWAY
SYNTHESIS_OF_PIPS_AT_THE_GOLGI_MEMBRANE
NUCLEAR_SIGNALING_BY_ERBB4
L1CAM_INTERA CTIONS
TRIF_MEDIATED_TLR3_SIGNALING
TRAF6_MEDIATED_NFKB_ACTIVATION
RECYCLING_PATHWAY_OF_L1
TRAFFICKING_OF_GLUR2_CONT AINING_AMPA_RECEPTORS
SYNTHESIS_OF_PC
PRE_NOTCH_PROCESSING_IN_GOLGI
XENOBIOTICS
ENERGY_DEPENDENT_REGULA TION_OF_MTOR_BY_LKB1_AMPK
ACTIVATED_AMPK_STIMULATES_FATTY_ACID_OXIDATION_IN_MUSCLE
ABCA_TRANSPOR TERS_IN_LIPID_HOMEOST ASIS
REGULATION_OF_IFNA_SIGNALING
GENERATION_OF_SECOND_MESSENGER_MOLECULES
INTERFERON_ALPHA_BETA_SIGNALING
METABOLISM_OF_STER OID_HORMONES_AND_VITAMINS_A_AND_D
STEROID_HORMONES
NEGATIVE_REGULATORS_OF_RIG_I_MDA5_SIGNALING
RIG_I_MDA5_MEDIATED_INDUCTION_OF_IFN_ALPHA_BET A_PATHWAYS
LIPOPROTEIN_METABOLISM
TERMINATION_OF_O_GLYCAN_BIOSYNTHESIS
CHYLOMICRON_MEDIATED_LIPID_TRANSPOR T
LIPID_DIGESTION_MOBILIZATION_AND_TRANSPOR T
NITRIC_OXIDE_STIMULATES_GUANYLATE_CYCLASE
CGMP_EFFECTS
INTEGRATION_OF_ENERGY_METABOLISM
OPIOID_SIGNALLING
REGULATION_OF_INSULIN_SECRETION
REGULATION_OF_INSULIN_SECRETION_BY_GLUCA GON_LIKE_PEPTIDE1
GLUCAGON_SIGNALING_IN_METABOLIC_REGULATION
G_ALPHA_Z_SIGNALLING_EVENTS
AMINE_COMPOUND_SLC_TRANSPOR TERS
NA_CL_DEPENDENT_NEUR OTRANSMITTER_TRANSPOR TERS
NETRIN1_SIGNALING
NUCLEAR_RECEPT OR_TRANSCRIPTION_PATHWAY
PLC_BETA_MEDIATED_EVENTS
OTHER_SEMAPHORIN_INTERA CTIONS
P130CAS_LINKA GE_TO_MAPK_SIGNALING_FOR_INTEGRINS
GRB2_SOS_PROVIDES_LINKA GE_TO_MAPK_SIGNALING_FOR_INTERGRINS_
STRIATED_MUSCLE_CONTRA CTION
MUSCLE_CONTRA CTION
IL_RECEPTOR_SHC_SIGNALING
SIGNALING_BY_RHO_GTPASES
VOLTAGE_GATED_POTASSIUM_CHANNELS
POTASSIUM_CHANNELS
GABA_RECEPTOR_ACTIVATION
GABA_B_RECEPT OR_ACTIVATION
CREB_PHOSPHORYLATION_THROUGH_THE_ACTIVATION_OF_RAS
POST_NMDA_RECEPTOR_ACTIVATION_EVENTS
ACTIVATION_OF_NMDA_RECEPTOR_UPON_GLUTAMATE_BINDING_AND_POSTSYNAPTIC_EVENTS
NEUROTRANSMITTER_RECEPT OR_BINDING_AND_DO WNSTREAM_TRANSMISSION_IN_THE_POSTSYNAPTIC_CELL
NEURONAL_SYSTEM
TRANSMISSION_A CROSS_CHEMICAL_SYNAPSES
TRAFFICKING_OF_AMPA_RECEPTORS
INTERACTION_BETWEEN_L1_AND_ANKYRINS
CD28_DEPENDENT_PI3K_AKT_SIGNALING
RAS_ACTIVATION_UOPN_CA2_INFUX_THR OUGH_NMDA_RECEPTOR
UNBLOCKING_OF_NMD A_RECEPTOR_GLUTAMATE_BINDING_AND_A CTIVATION
PEPTIDE_LIGAND_BINDING_RECEPT ORS
CLASS_A1_RHODOPSIN_LIKE_RECEPT ORS
GPCR_LIGAND_BINDING
G_ALPHA_I_SIGNALLING_EVENTS
PLATELET_ACTIVATION_SIGNALING_AND_A GGREGATION
RESPONSE_TO_ELEVATED_PLATELET_CYTOSOLIC_CA2_
IMMUNOREGULATORY_INTERACTIONS_BETWEEN_A_LYMPHOID_AND_A_NON_LYMPHOID_CELL
PHOSPHORYLATION_OF_CD3_AND_TCR_ZET A_CHAINS
PD1_SIGNALING
PLATELET_AGGREGATION_PLUG_FORMATION
INTEGRIN_ALPHAIIB_BETA3_SIGNALING
HEMOSTASIS
INTEGRIN_CELL_SURF ACE_INTERACTIONS
CHEMOKINE_RECEPT ORS_BIND_CHEMOKINES
IL_3_5_AND_GM_CSF_SIGNALING
INFLAMMASOMES
INTERFERON_GAMMA_SIGNALING
INNATE_IMMUNE_SYSTEM
COSTIMULATION_BY_THE_CD28_F AMILY
NUCLEOTIDE_LIKE_PURINERGIC_RECEPT ORS
ANTIGEN_ACTIVATES_B_CELL_RECEPT OR_LEADING_TO_GENERATION_OF_SECOND_MESSENGERS
ION_CHANNEL_TRANSPOR T
ION_TRANSPORT_BY_P_TYPE_ATPASES
TRANSMEMBRANE_TRANSPOR T_OF_SMALL_MOLECULES
FGFR_LIGAND_BINDING_AND_A CTIVATION
NEUROTRANSMITTER_RELEASE_CYCLE
GLUTAMATE_NEUROTRANSMITTER_RELEASE_CYCLE
PLATELET_SENSITIZATION_BY_LDL
TRIGLYCERIDE_BIOSYNTHESIS
DARPP_32_EVENTS
SYNTHESIS_OF_PIPS_AT_THE_PLASMA_MEMBRANE
PI_METABOLISM
PLATELET_HOMEOSTASIS
GLYCEROPHOSPHOLIPID_BIOSYNTHESIS
PHOSPHOLIPID_METABOLISM
METABOLISM_OF_LIPIDS_AND_LIPOPR OTEINS
EFFECTS_OF_PIP2_HYDR OLYSIS
INTRINSIC_PATHWAY
FORMATION_OF_FIBRIN_CLO T_CLOTTING_CASCADE
ABC_FAMILY_PROTEINS_MEDIATED_TRANSPORT
G_ALPHA_S_SIGNALLING_EVENTS
RAP1_SIGNALLING
COMPLEMENT_CASCADE
AQUAPORIN_MEDIATED_TRANSPORT
REGULATION_OF_WATER_BALANCE_BY_RENAL_A QUAPORINS
PHOSPHOLIPASE_C_MEDIATED_CASCADE
PKA_MEDIATED_PHOSPHORYLATION_OF_CREB
CA_DEPENDENT_EVENTS
DAG_AND_IP3_SIGNALING
PHASE1_FUNCTIONALIZA TION_OF_COMPOUNDS
BIOLOGICAL_OXIDATIONS
RIP_MEDIATED_NFKB_ACTIVATION_VIA_DAI
TAK1_ACTIVATES_NFKB_BY_PHOSPHOR YLATION_AND_ACTIVATION_OF_IKKS_COMPLEX
CYTOCHROME_P450_ARRANGED_BY_SUBSTRA TE_TYPE
ENDOGENOUS_STER OLS
GOLGI_ASSOCIATED_VESICLE_BIOGENESIS
TRANS_GOLGI_NETW ORK_VESICLE_B UDDING
TRANSPORT_OF_VITAMINS_NUCLEOSIDES_AND_RELA TED_MOLECULES
LYSOSOME_VESICLE_BIOGENESIS
PLATELET_CALCIUM_HOMEOST ASIS
ACTIVATED_NOTCH1_TRANSMITS_SIGNAL_T O_THE_NUCLEUS
BILE_ACID_AND_BILE_SALT_METABOLISM
SYNTHESIS_OF_BILE_A CIDS_AND_BILE_SALTS
SYNTHESIS_OF_BILE_A CIDS_AND_BILE_SALTS_VIA_7ALPHA_HYDR OXYCHOLESTER OL
ACYL_CHAIN_REMODELLING_OF_PS
ACYL_CHAIN_REMODELLING_OF_PG
SYNTHESIS_OF_PA
ACYL_CHAIN_REMODELLING_OF_PI
ACYL_CHAIN_REMODELLING_OF_PE
ACYL_CHAIN_REMODELLING_OF_PC
Molecular Pathways
−2
Wavelet_HLL_rlgl_lowGrayLevelRunEmphasis
Wavelet_HLL_rlgl_shortRunLowGrayLevEmpha
Wavelet_LHH_rlgl_longRunLowGrayLevEmpha
Wavelet_HHH_rlgl_lowGrayLevelRunEmphasis
Wavelet_HHH_rlgl_shortRunLowGrayLevEmpha
Wavelet_LHL_rlgl_lowGrayLevelRunEmphasis
Wavelet_LHL_rlgl_shortRunLowGrayLevEmpha
Wavelet_LLH_rlgl_lowGrayLevelRunEmphasis
Wavelet_LLH_rlgl_shortRunLowGrayLevEmpha
Wavelet_HHH_rlgl_longRunLowGrayLevEmpha
Wavelet_HHL_rlgl_longRunLowGrayLevEmpha
Wavelet_HLH_rlgl_longRunLowGrayLevEmpha
Wavelet_LHH_glcm_infoCorr2
Wavelet_HHH_glcm_infoCorr2
Wavelet_HHL_stats_median
Wavelet_HLH_stats_median
GLSZM_zonePercentage
Wavelet_LLH_stats_min
Wavelet_LHL_stats_min
Wavelet_LLL_rlgl_longRunLowGrayLevEmpha
RLGL_longRunLowGrayLevEmpha
GLCM_clusShade
Wavelet_LLL_glcm_clusShade
Wavelet_LHH_stats_median
Wavelet_LHH_stats_mean
Wavelet_HLL_stats_entropy
Wavelet_HLL_glcm_sumEntro
Wavelet_HLL_glcm_entrop2
Wavelet_HLL_glcm_dissimilar
Wavelet_HLL_glcm_diffEntro
Wavelet_HLL_glcm_contrast
Wavelet_LHH_glcm_clusProm
Wavelet_HLH_glcm_clusProm
Wavelet_HHL_glcm_clusProm
Wavelet_LHL_glcm_clusProm
Wavelet_LLH_glcm_clusProm
GLCM_sumEntro
Wavelet_LLL_glcm_sumEntro
Stats_entropy
Wavelet_LLL_stats_entropy
Wavelet_LLL_glcm_entrop2
GLCM_entrop2
Stats_skewness
Wavelet_LLL_stats_skewness
Wavelet_LLL_rlgl_shortRunLowGrayLevEmpha
Wavelet_LLL_rlgl_lowGrayLevelRunEmphasis
RLGL_lowGrayLevelRunEmphasis
RLGL_shortRunLowGrayLevEmpha
Wavelet_LHH_stats_min
Wavelet_LHH_rlgl_lowGrayLevelRunEmphasis
Wavelet_LHH_rlgl_shortRunLowGrayLevEmpha
Wavelet_HHL_rlgl_lowGrayLevelRunEmphasis
Wavelet_HHL_rlgl_shortRunLowGrayLevEmpha
Shape_surfVolRatio
Wavelet_HLH_rlgl_lowGrayLevelRunEmphasis
Wavelet_HLH_rlgl_shortRunLowGrayLevEmpha
RLGL_shortRunEmphasis
RLGL_runPercentage
Wavelet_LLL_rlgl_shortRunEmphasis
Wavelet_LLL_rlgl_runPercentage
Wavelet_HLL_rlgl_shortRunEmphasis
Wavelet_HLL_rlgl_runPercentage
Wavelet_LLL_glcm_contrast
GLCM_contrast
GLCM_dissimilar
Wavelet_LLL_glcm_dissimilar
GLCM_diffEntro
Wavelet_LLL_glcm_diffEntro
LoG_sigma_0_5_mm_3D_stats_mean
LoG_sigma_0_5_mm_3D_stats_meanPos
LoG_sigma_1_5_mm_3D_stats_meanPos
LoG_sigma_1_mm_3D_stats_meanPos
LoG_sigma_2_mm_3D_stats_mean
LoG_sigma_2_mm_3D_stats_meanPos
LoG_sigma_3_mm_3D_stats_meanPos
LoG_sigma_4_mm_3D_stats_meanPos
LoG_sigma_4_5_mm_3D_stats_meanPos
LoG_sigma_3_5_mm_3D_stats_mean
LoG_sigma_3_5_mm_3D_stats_meanPos
LoG_sigma_2_5_mm_3D_stats_meanPos
LoG_sigma_5_mm_3D_stats_mean
LoG_sigma_5_mm_3D_stats_meanPos
LoG_sigma_1_5_mm_3D_stats_mean
LoG_sigma_1_mm_3D_stats_mean
LoG_sigma_2_5_mm_3D_stats_mean
LoG_sigma_3_mm_3D_stats_mean
LoG_sigma_4_mm_3D_stats_mean
LoG_sigma_4_5_mm_3D_stats_mean
LoG_sigma_0_5_mm_2D_stats_meanPos
LoG_sigma_1_5_mm_2D_stats_meanPos
LoG_sigma_1_mm_2D_stats_mean
LoG_sigma_1_mm_2D_stats_meanPos
LoG_sigma_2_mm_2D_stats_meanPos
LoG_sigma_2_5_mm_2D_stats_meanPos
LoG_sigma_3_5_mm_2D_stats_meanPos
LoG_sigma_3_mm_2D_stats_meanPos
LoG_sigma_4_5_mm_2D_stats_mean
LoG_sigma_4_5_mm_2D_stats_meanPos
LoG_sigma_4_mm_2D_stats_meanPos
LoG_sigma_5_mm_2D_stats_meanPos
LoG_sigma_0_5_mm_2D_stats_mean
LoG_sigma_1_5_mm_2D_stats_mean
LoG_sigma_2_mm_2D_stats_mean
LoG_sigma_2_5_mm_2D_stats_mean
LoG_sigma_3_5_mm_2D_stats_mean
LoG_sigma_3_mm_2D_stats_mean
LoG_sigma_4_mm_2D_stats_mean
LoG_sigma_5_mm_2D_stats_mean
Wavelet_LHH_glcm_contrast
Wavelet_LHH_glcm_clusTend
Wavelet_LHH_glcm_entrop2
Wavelet_LHH_glcm_dissimilar
Wavelet_LHH_glcm_diffEntro
Wavelet_LHH_glcm_sumEntro
Wavelet_LHH_stats_entropy
Wavelet_LHH_rlgl_runPercentage
Wavelet_LHH_rlgl_shortRunEmphasis
Wavelet_HHH_rlgl_shortRunEmphasis
Wavelet_HHH_rlgl_runPercentage
Wavelet_HHL_rlgl_runPercentage
Wavelet_HHL_rlgl_shortRunEmphasis
Wavelet_LHL_glcm_clusTend
Wavelet_LHL_glcm_contrast
Wavelet_LHL_glcm_entrop2
Wavelet_LHL_glcm_dissimilar
Wavelet_LHL_glcm_diffEntro
Wavelet_LHL_glcm_sumEntro
Wavelet_LHL_stats_entropy
Wavelet_HHL_glcm_clusTend
Wavelet_HHL_glcm_sumEntro
Wavelet_HHL_glcm_contrast
Wavelet_HHL_stats_entropy
Wavelet_HHL_glcm_entrop2
Wavelet_HHL_glcm_dissimilar
Wavelet_HHL_glcm_diffEntro
Wavelet_HHH_glcm_clusProm
Wavelet_HHH_glcm_entrop2
Wavelet_HHH_glcm_clusTend
Wavelet_HHH_glcm_dissimilar
Wavelet_HHH_glcm_diffEntro
Wavelet_HHH_glcm_sumEntro
Wavelet_HHH_glcm_contrast
Wavelet_HHH_stats_entropy
Wavelet_HLH_glcm_clusTend
Wavelet_HLH_glcm_sumEntro
Wavelet_HLH_glcm_dissimilar
Wavelet_HLH_glcm_diffEntro
Wavelet_HLH_glcm_contrast
Wavelet_HLH_stats_entropy
Wavelet_HLH_glcm_entrop2
Wavelet_HLH_rlgl_runPercentage
Wavelet_HLH_rlgl_shortRunEmphasis
Wavelet_LLH_rlgl_runPercentage
Wavelet_LLH_rlgl_shortRunEmphasis
Wavelet_LHL_rlgl_runPercentage
Wavelet_LHL_rlgl_shortRunEmphasis
Wavelet_LLH_glcm_clusTend
Wavelet_LLH_glcm_contrast
Wavelet_LLH_glcm_dissimilar
Wavelet_LLH_glcm_diffEntro
Wavelet_LLH_glcm_sumEntro
Wavelet_LLH_stats_entropy
Wavelet_LLH_glcm_entrop2
Wavelet_HLL_glcm_infoCorr2
Wavelet_HLL_glcm_correl1
Wavelet_HLL_stats_min
Wavelet_HLH_glcm_correl1
Wavelet_HHL_glcm_correl1
GLCM_infoCorr2
Wavelet_LLL_glcm_infoCorr2
Wavelet_LHL_rlgl_longRunLowGrayLevEmpha
Wavelet_LLH_rlgl_longRunLowGrayLevEmpha
Wavelet_LLH_glcm_clusShade
Wavelet_LLH_stats_skewness
Wavelet_LHL_stats_skewness
Shape_compactness2
Shape_sphericity
Wavelet_HLH_stats_min
Wavelet_HHL_stats_min
Wavelet_HHH_stats_min
Wavelet_HLH_glcm_infoCorr2
Wavelet_HHL_glcm_infoCorr2
Wavelet_LHL_glcm_infoCorr2
Wavelet_LLH_glcm_infoCorr2
Wavelet_HLL_glcm_clusTend
Wavelet_HLL_glcm_clusProm
Wavelet_HHL_glcm_clusShade
GLSZM_intensityVariability
GLSZM_lowIntensityEmphasis
GLSZM_lowIntensitySmallAreaEmp
Wavelet_LHH_glcm_clusShade
Wavelet_LHH_stats_skewness
Wavelet_LLL_glcm_clusTend
GLCM_clusTend
Wavelet_LLL_stats_md
Stats_md
Wavelet_LLL_stats_std
Wavelet_LLL_stats_var
Stats_std
Stats_var
LoG_sigma_3_5_mm_3D_stats_std
LoG_sigma_3_mm_3D_stats_std
LoG_sigma_2_5_mm_3D_stats_std
LoG_sigma_2_mm_3D_stats_std
LoG_sigma_1_mm_3D_stats_std
LoG_sigma_0_5_mm_3D_stats_std
LoG_sigma_1_5_mm_3D_stats_std
LoG_sigma_4_5_mm_3D_stats_std
LoG_sigma_4_mm_3D_stats_std
LoG_sigma_5_mm_3D_stats_std
LoG_sigma_5_mm_2D_stats_std
LoG_sigma_4_5_mm_2D_stats_std
LoG_sigma_4_mm_2D_stats_std
LoG_sigma_3_5_mm_2D_stats_std
LoG_sigma_3_mm_2D_stats_std
LoG_sigma_2_5_mm_2D_stats_std
LoG_sigma_2_mm_2D_stats_std
LoG_sigma_1_mm_2D_stats_std
LoG_sigma_0_5_mm_2D_stats_std
LoG_sigma_1_5_mm_2D_stats_std
Wavelet_HLL_stats_md
Wavelet_HLL_stats_rms
Wavelet_HLL_stats_std
Wavelet_HLL_stats_var
Wavelet_HLH_stats_rms
Wavelet_HLH_stats_std
Wavelet_HLH_stats_var
Wavelet_HHH_stats_rms
Wavelet_HHH_stats_std
Wavelet_HHH_stats_var
Wavelet_HHL_stats_md
Wavelet_HHH_stats_md
Wavelet_HLH_stats_md
Wavelet_HHL_stats_rms
Wavelet_HHL_stats_std
Wavelet_HHL_stats_var
Wavelet_LHL_stats_std
Wavelet_LHL_stats_var
Wavelet_LHL_stats_rms
Wavelet_LHH_stats_rms
Wavelet_LHH_stats_std
Wavelet_LHH_stats_var
Wavelet_LHL_stats_md
Wavelet_LHH_stats_md
Wavelet_LLH_stats_md
Wavelet_LLH_stats_rms
Wavelet_LLH_stats_std
Wavelet_LLH_stats_var
Wavelet_HHL_stats_mean
Wavelet_HLH_stats_mean
Stats_min
Wavelet_LLL_stats_min
GLCM_infoCorr1
Wavelet_LLL_glcm_infoCorr1
Wavelet_LLH_glcm_infoCorr1
Wavelet_HLL_glcm_infoCorr1
LoG_sigma_5_mm_2D_stats_entropy
LoG_sigma_5_mm_2D_stats_entropyPos
LoG_sigma_5_mm_3D_stats_entropyPos
LoG_sigma_4_mm_2D_stats_entropy
LoG_sigma_4_mm_2D_stats_entropyPos
LoG_sigma_4_5_mm_2D_stats_entropyPos
LoG_sigma_3_5_mm_2D_stats_entropyPos
LoG_sigma_3_mm_2D_stats_entropyPos
LoG_sigma_2_5_mm_2D_stats_entropy
LoG_sigma_2_5_mm_2D_stats_entropyPos
LoG_sigma_1_5_mm_2D_stats_entropyPos
LoG_sigma_2_mm_2D_stats_entropyPos
LoG_sigma_2_mm_2D_stats_entropy
LoG_sigma_0_5_mm_2D_stats_entropyPos
LoG_sigma_1_mm_2D_stats_entropyPos
LoG_sigma_4_5_mm_3D_stats_entropy
LoG_sigma_5_mm_3D_stats_entropy
LoG_sigma_4_mm_3D_stats_entropy
LoG_sigma_3_mm_3D_stats_entropy
LoG_sigma_2_5_mm_3D_stats_entropy
LoG_sigma_2_mm_3D_stats_entropy
LoG_sigma_1_5_mm_3D_stats_entropy
LoG_sigma_1_mm_3D_stats_entropy
LoG_sigma_1_mm_2D_stats_entropy
LoG_sigma_0_5_mm_2D_stats_entropy
LoG_sigma_1_5_mm_2D_stats_entropy
LoG_sigma_3_5_mm_2D_stats_entropy
LoG_sigma_4_5_mm_2D_stats_entropy
LoG_sigma_3_mm_2D_stats_entropy
LoG_sigma_4_5_mm_3D_stats_entropyPos
LoG_sigma_4_mm_3D_stats_entropyPos
LoG_sigma_3_mm_3D_stats_entropyPos
LoG_sigma_3_5_mm_3D_stats_entropy
LoG_sigma_3_5_mm_3D_stats_entropyPos
LoG_sigma_2_mm_3D_stats_entropyPos
LoG_sigma_2_5_mm_3D_stats_entropyPos
LoG_sigma_1_mm_3D_stats_entropyPos
LoG_sigma_1_5_mm_3D_stats_entropyPos
LoG_sigma_0_5_mm_3D_stats_entropy
LoG_sigma_0_5_mm_3D_stats_entropyPos
LoG_sigma_2_5_mm_2D_stats_uniformity
LoG_sigma_3_mm_2D_stats_uniformity
LoG_sigma_4_5_mm_2D_stats_uniformity
LoG_sigma_3_5_mm_2D_stats_uniformity
LoG_sigma_0_5_mm_2D_stats_uniformity
LoG_sigma_1_5_mm_2D_stats_uniformity
LoG_sigma_1_mm_2D_stats_uniformity
LoG_sigma_0_5_mm_3D_stats_uniformity
LoG_sigma_2_mm_3D_stats_uniformity
LoG_sigma_2_5_mm_3D_stats_uniformity
LoG_sigma_5_mm_3D_stats_uniformity
LoG_sigma_3_5_mm_3D_stats_uniformity
LoG_sigma_0_5_mm_3D_stats_uniformityPos
LoG_sigma_1_5_mm_3D_stats_uniformity
LoG_sigma_1_5_mm_3D_stats_uniformityPos
LoG_sigma_1_mm_3D_stats_uniformity
LoG_sigma_1_mm_3D_stats_uniformityPos
LoG_sigma_2_mm_3D_stats_uniformityPos
LoG_sigma_2_5_mm_3D_stats_uniformityPos
LoG_sigma_3_mm_3D_stats_uniformity
LoG_sigma_3_mm_3D_stats_uniformityPos
LoG_sigma_3_5_mm_3D_stats_uniformityPos
LoG_sigma_3_5_mm_2D_stats_uniformityPos
LoG_sigma_4_mm_2D_stats_uniformityPos
LoG_sigma_4_5_mm_2D_stats_uniformityPos
LoG_sigma_4_mm_2D_stats_uniformity
LoG_sigma_3_mm_2D_stats_uniformityPos
LoG_sigma_5_mm_2D_stats_uniformity
LoG_sigma_5_mm_2D_stats_uniformityPos
LoG_sigma_0_5_mm_2D_stats_uniformityPos
LoG_sigma_1_5_mm_2D_stats_uniformityPos
LoG_sigma_1_mm_2D_stats_uniformityPos
LoG_sigma_2_mm_2D_stats_uniformity
LoG_sigma_2_mm_2D_stats_uniformityPos
LoG_sigma_2_5_mm_2D_stats_uniformityPos
LoG_sigma_4_5_mm_3D_stats_uniformity
LoG_sigma_4_5_mm_3D_stats_uniformityPos
LoG_sigma_5_mm_3D_stats_uniformityPos
LoG_sigma_4_mm_3D_stats_uniformity
LoG_sigma_4_mm_3D_stats_uniformityPos
Wavelet_HLH_rlgl_longRunHighGrayLevEmpha
Wavelet_LLH_glcm_invDiffnorm
Wavelet_LLH_glcm_invDiffmomnor
Wavelet_LLH_stats_kurtosis
Wavelet_HHL_rlgl_longRunHighGrayLevEmpha
Wavelet_LHH_rlgl_longRunHighGrayLevEmpha
Wavelet_LLH_rlgl_longRunHighGrayLevEmpha
GLCM_invDiffmomnor
Wavelet_LLL_glcm_invDiffmomnor
GLCM_invDiffnorm
Wavelet_LLL_glcm_invDiffnorm
Wavelet_LHL_rlgl_longRunEmphasis
Wavelet_LLH_rlgl_longRunEmphasis
Wavelet_LHH_stats_kurtosis
Wavelet_LHH_glcm_invDiffmomnor
Wavelet_LHH_glcm_invDiffnorm
Wavelet_HHL_glcm_invDiffnorm
Wavelet_HHL_glcm_invDiffmomnor
Wavelet_HHL_stats_kurtosis
Wavelet_LHL_glcm_invDiffnorm
Wavelet_LHL_glcm_invDiffmomnor
Wavelet_LHL_stats_kurtosis
Wavelet_HLH_glcm_invDiffmomnor
Wavelet_HLH_glcm_invDiffnorm
Wavelet_HLH_stats_kurtosis
Wavelet_HHH_glcm_invDiffnorm
Wavelet_HHH_glcm_invDiffmomnor
Wavelet_HLH_rlgl_longRunEmphasis
Wavelet_HLH_glcm_maxProb
Wavelet_HLH_glcm_energy
Wavelet_HLH_stats_uniformity
Wavelet_HLH_glcm_homogeneity1
Wavelet_HLH_glcm_homogeneity2
Wavelet_LLH_glcm_inverseVar
Wavelet_HLH_glcm_inverseVar
Wavelet_LLH_stats_uniformity
Wavelet_LLH_glcm_energy
Wavelet_LLH_glcm_maxProb
Wavelet_LLH_glcm_homogeneity2
Wavelet_LLH_glcm_homogeneity1
Wavelet_LHL_glcm_homogeneity1
Wavelet_LHL_glcm_homogeneity2
Wavelet_LHL_glcm_maxProb
Wavelet_LHL_glcm_energy
Wavelet_LHL_stats_uniformity
Wavelet_LHL_glcm_inverseVar
Wavelet_HHL_glcm_homogeneity2
Wavelet_HHL_glcm_homogeneity1
Wavelet_HHL_glcm_maxProb
Wavelet_HHL_rlgl_longRunEmphasis
Wavelet_HHL_glcm_energy
Wavelet_HHL_stats_uniformity
Wavelet_HHL_glcm_inverseVar
Wavelet_HHH_stats_uniformity
Wavelet_HHH_glcm_inverseVar
Wavelet_HHH_glcm_energy
Wavelet_HHH_glcm_homogeneity2
Wavelet_HHH_glcm_homogeneity1
Wavelet_HHH_rlgl_longRunEmphasis
Wavelet_HHH_glcm_maxProb
Wavelet_HHH_stats_kurtosis
Wavelet_LHH_glcm_homogeneity1
Wavelet_LHH_glcm_homogeneity2
Wavelet_LHH_glcm_inverseVar
Wavelet_LHH_glcm_energy
Wavelet_LHH_stats_uniformity
Wavelet_LHH_glcm_maxProb
Wavelet_LHH_rlgl_longRunEmphasis
LoG_sigma_5_mm_3D_stats_skewness
LoG_sigma_4_5_mm_3D_stats_skewness
LoG_sigma_4_mm_2D_stats_skewness
LoG_sigma_3_5_mm_2D_stats_skewness
LoG_sigma_5_mm_2D_stats_skewness
LoG_sigma_4_5_mm_2D_stats_skewness
LoG_sigma_0_5_mm_2D_stats_skewness
LoG_sigma_1_5_mm_2D_stats_skewness
LoG_sigma_1_mm_2D_stats_skewness
LoG_sigma_2_mm_2D_stats_skewness
LoG_sigma_3_mm_2D_stats_skewness
LoG_sigma_2_5_mm_2D_stats_skewness
LoG_sigma_0_5_mm_3D_stats_skewness
LoG_sigma_1_5_mm_3D_stats_skewness
LoG_sigma_1_mm_3D_stats_skewness
LoG_sigma_2_mm_3D_stats_skewness
LoG_sigma_2_5_mm_3D_stats_skewness
LoG_sigma_3_mm_3D_stats_skewness
LoG_sigma_4_mm_3D_stats_skewness
LoG_sigma_3_5_mm_3D_stats_skewness
LoG_sigma_5_mm_3D_stats_kurtosis
LoG_sigma_4_5_mm_3D_stats_kurtosis
LoG_sigma_5_mm_2D_stats_kurtosis
LoG_sigma_4_5_mm_2D_stats_kurtosis
LoG_sigma_4_mm_2D_stats_kurtosis
LoG_sigma_4_mm_3D_stats_kurtosis
LoG_sigma_3_5_mm_3D_stats_kurtosis
LoG_sigma_3_mm_3D_stats_kurtosis
LoG_sigma_2_5_mm_3D_stats_kurtosis
LoG_sigma_2_mm_3D_stats_kurtosis
LoG_sigma_1_mm_3D_stats_kurtosis
LoG_sigma_0_5_mm_3D_stats_kurtosis
LoG_sigma_1_5_mm_3D_stats_kurtosis
LoG_sigma_3_5_mm_2D_stats_kurtosis
LoG_sigma_3_mm_2D_stats_kurtosis
LoG_sigma_2_5_mm_2D_stats_kurtosis
LoG_sigma_2_mm_2D_stats_kurtosis
LoG_sigma_1_mm_2D_stats_kurtosis
LoG_sigma_0_5_mm_2D_stats_kurtosis
LoG_sigma_1_5_mm_2D_stats_kurtosis
Wavelet_LLL_stats_rms
Stats_rms
Wavelet_LLL_stats_mean
Stats_mean
RLGL_longRunHighGrayLevEmpha
Wavelet_LLL_rlgl_longRunHighGrayLevEmpha
RLGL_longRunEmphasis
GLCM_homogeneity1
GLCM_homogeneity2
Wavelet_LLL_rlgl_longRunEmphasis
Wavelet_LLL_glcm_homogeneity1
Wavelet_LLL_glcm_homogeneity2
Wavelet_LLL_stats_kurtosis
Stats_kurtosis
Wavelet_LLL_stats_median
Stats_median
Wavelet_LLL_glcm_energy
GLCM_energy
GLCM_maxProb
Wavelet_LLL_glcm_maxProb
Stats_uniformity
Wavelet_LLL_stats_uniformity
Wavelet_HLL_glcm_invDiffnorm
Wavelet_HLL_glcm_invDiffmomnor
GLCM_inverseVar
Wavelet_HLL_rlgl_longRunEmphasis
Wavelet_HLL_glcm_homogeneity1
Wavelet_HLL_glcm_homogeneity2
Wavelet_HLL_stats_kurtosis
Wavelet_HLL_stats_uniformity
Wavelet_HLL_glcm_maxProb
Wavelet_HLL_glcm_energy
Wavelet_LHH_rlgl_grayLevelNonuniformity
Wavelet_LLH_rlgl_grayLevelNonuniformity
Wavelet_LHL_rlgl_grayLevelNonuniformity
Wavelet_HHL_rlgl_grayLevelNonuniformity
Wavelet_HHH_rlgl_grayLevelNonuniformity
Wavelet_HLH_rlgl_grayLevelNonuniformity
Shape_compactness
Wavelet_HLL_rlgl_runLengthNonuniformity
Shape_volume
Shape_surface
RLGL_grayLevelNonuniformity
Wavelet_LLL_rlgl_grayLevelNonuniformity
Wavelet_HLL_rlgl_grayLevelNonuniformity
Wavelet_LHH_rlgl_runLengthNonuniformity
Wavelet_HHH_rlgl_runLengthNonuniformity
Stats_energy
Stats_totalenergy
Wavelet_LLL_stats_energy
Wavelet_LLL_stats_totalenergy
Wavelet_HLL_stats_energy
Wavelet_HLL_stats_totalenergy
Shape_maxDiameter3D
Shape_maxDiameter3D_pdist
Shape_maxDiameter2Dy
Shape_maxDiameter2Dx
Wavelet_LHL_stats_energy
Wavelet_LHL_stats_totalenergy
Wavelet_LHH_stats_energy
Wavelet_LHH_stats_totalenergy
Wavelet_HLL_rlgl_longRunHighGrayLevEmpha
Shape_voxelNum
RLGL_runLengthNonuniformity
Wavelet_LLL_rlgl_runLengthNonuniformity
Shape_maxDiameter2Dz
Wavelet_HLH_rlgl_runLengthNonuniformity
Wavelet_HHL_rlgl_runLengthNonuniformity
Wavelet_LLH_rlgl_runLengthNonuniformity
Wavelet_LHL_rlgl_runLengthNonuniformity
Wavelet_HLH_glcm_autocorr
Wavelet_HLH_glcm_sumAvg
Wavelet_HLH_glcm_sumSquares
Wavelet_HLH_glcm_sumVar
Wavelet_HLH_rlgl_highGrayLevelRunEmphasis
Wavelet_HHL_glcm_sumVar
Wavelet_HHL_glcm_sumAvg
Wavelet_HHL_rlgl_highGrayLevelRunEmphasis
Wavelet_HHL_glcm_sumSquares
Wavelet_HHL_glcm_autocorr
Wavelet_LLL_stats_range
Stats_range
GLSZM_highIntensityEmphasis
Wavelet_HLH_rlgl_shortRunHighGrayLevEmpha
Wavelet_HHL_rlgl_shortRunHighGrayLevEmpha
Wavelet_LHH_rlgl_shortRunHighGrayLevEmpha
Wavelet_LHH_glcm_sumSquares
Wavelet_LHH_rlgl_highGrayLevelRunEmphasis
Wavelet_LHH_glcm_sumVar
Wavelet_LHH_glcm_sumAvg
Wavelet_LHH_glcm_autocorr
GLSZM_sizeZoneVariability
Wavelet_LHH_stats_max
GLSZM_highIntensitySmallAreaEmp
Wavelet_LHH_stats_range
Wavelet_LLH_stats_range
GLCM_autocorr
GLCM_sumSquares
GLCM_sumAvg
RLGL_highGrayLevelRunEmphasis
GLCM_sumVar
Wavelet_LLL_rlgl_highGrayLevelRunEmphasis
Wavelet_LLL_glcm_sumAvg
Wavelet_LLL_glcm_sumVar
Wavelet_LLL_glcm_autocorr
Wavelet_LLL_glcm_sumSquares
Wavelet_LHL_stats_max
Wavelet_LHL_stats_range
Wavelet_HHH_rlgl_longRunHighGrayLevEmpha
Wavelet_LHL_rlgl_longRunHighGrayLevEmpha
Wavelet_LLL_rlgl_shortRunHighGrayLevEmpha
RLGL_shortRunHighGrayLevEmpha
Wavelet_LLH_stats_max
Wavelet_LLH_stats_energy
Wavelet_LLH_stats_totalenergy
Wavelet_LLL_stats_max
Stats_max
Wavelet_LLH_stats_median
Wavelet_LHL_stats_median
Wavelet_LLH_stats_mean
Wavelet_LHL_stats_mean
Wavelet_HLL_stats_mean
Wavelet_HLL_stats_median
Wavelet_LLL_glcm_clusProm
GLCM_clusProm
Wavelet_LLL_glcm_correl1
GLCM_correl1
Wavelet_HLL_glcm_sumAvg
Wavelet_HLL_rlgl_highGrayLevelRunEmphasis
Wavelet_HLL_glcm_sumSquares
Wavelet_HLL_glcm_autocorr
Wavelet_HLL_glcm_sumVar
Wavelet_LHL_glcm_clusShade
Wavelet_HLL_rlgl_longRunLowGrayLevEmpha
Wavelet_HHH_stats_median
Wavelet_HHH_stats_mean
Wavelet_HHL_stats_skewness
Wavelet_LHL_glcm_correl1
Wavelet_LLH_glcm_correl1
Wavelet_HHH_rlgl_shortRunHighGrayLevEmpha
Wavelet_HHH_rlgl_highGrayLevelRunEmphasis
Wavelet_HHH_glcm_sumSquares
Wavelet_HHH_glcm_autocorr
Wavelet_HHH_glcm_sumVar
Wavelet_HHH_glcm_sumAvg
Wavelet_LHL_rlgl_highGrayLevelRunEmphasis
Wavelet_LHL_glcm_sumSquares
Wavelet_LHL_glcm_sumVar
Wavelet_LHL_glcm_autocorr
Wavelet_LHL_glcm_sumAvg
Wavelet_LLH_rlgl_highGrayLevelRunEmphasis
Wavelet_LLH_glcm_sumSquares
Wavelet_LLH_glcm_sumVar
Wavelet_LLH_glcm_sumAvg
Wavelet_LLH_glcm_autocorr
Wavelet_HLL_rlgl_shortRunHighGrayLevEmpha
Wavelet_LLH_rlgl_shortRunHighGrayLevEmpha
Wavelet_LHL_rlgl_shortRunHighGrayLevEmpha
Shape_spherDisprop
Wavelet_LLL_glcm_inverseVar
Wavelet_HLL_glcm_inverseVar
Wavelet_HHL_glcm_infoCorr1
Wavelet_HLH_glcm_infoCorr1
Wavelet_LHL_glcm_infoCorr1
Wavelet_HHH_glcm_correl1
Wavelet_LHH_glcm_correl1
Wavelet_HHH_glcm_clusShade
Wavelet_HHH_stats_skewness
Wavelet_HLL_stats_skewness
Wavelet_HLL_glcm_clusShade
GLSZM_smallAreaEmphasis
Wavelet_HLH_glcm_clusShade
Wavelet_HLH_stats_skewness
GLSZM_lowIntensityLargeAreaEmp
GLSZM_largeAreaEmphasis
GLSZM_highIntensityLarteAreaEmp
Wavelet_HHH_glcm_infoCorr1
Wavelet_LHH_glcm_infoCorr1
Wavelet_HLH_stats_energy
Wavelet_HLH_stats_totalenergy
Wavelet_HHL_stats_energy
Wavelet_HHL_stats_totalenergy
Wavelet_HHH_stats_energy
Wavelet_HHH_stats_totalenergy
Wavelet_HHL_stats_range
Wavelet_HHL_stats_max
Wavelet_HHH_stats_range
Wavelet_HHH_stats_max
Wavelet_HLL_stats_max
Wavelet_HLL_stats_range
Wavelet_HLH_stats_range
Wavelet_HLH_stats_max
(A)
Radiomic Features
Strong correlation between Radiomic data and Molecular Pathways
11
Radiomics-Genomics association modules
13 association modules were identified
and independently validated
Radiomics Modules associate with
distinct biological processes
Modules are significantly associated with
clinical parameters:
survival (3), histology (5), stage (10)
Genomic Signature:
Hou et al., 2010
17 genes for
Post-treatment survival
Radiomics Signature:
Aerts et al., 2014
(I) Statistics Energy
(II) Shape Compactness
(III) Grey Level Nonuniformity
(IV) Wavelet Grey Level
Nonuniformity HLH
Prognostic Power (Concordance Index)
Clinical-Radiomics-Genomics Prognostic Signatures
Radiomics significantly adds to prognostic gene-signatures
Imaging-Genomics in GBM
12
Methods: Manual delineations
B
A
Manual slice-by-slice
contouring of the abnormal
signal on T1c and FLAIR images
FAST algorithm to segment
contrast-enhancing and
necrotic sub-volumes on T1c
C
Necrosis
Contrast Enhancement
Edema
Tumor Bulk
Total Tumor Volume
Tutal
Final contours were all
manually reviewed and edited
by expert neuro-radiologists
PAGE 37
*Grossmann et al. Submitted
Prognostic value of volumetric features
*Grossmann et al. Submitted
Imaging-Genomics Pathway Analysis of MRI Derived Volumetric
Tumor Phenotype Features in Glioblastoma
n=96 GBM patients
from TCGA-GBM
cohort
13
Volumetric features predict mutational status in
GBM patients
N=76 GBM patients
from TCGA-GBM
cohort
*Gutman et al. Submitted
TP53 positive/negative
TP53 mutated tumors had
significantly smaller CE
and necrotic volumes
(p=0.012 and 0.017,
respectively) compared to
wild-type.
*Gutman et al. Submitted
Quantitative Imaging: Current Status & Outlook
-
Imaging moves towards a computational data science (bioinformatics)
-
Due to advances in imaging, quantitative imaging is currently possible
-
Large retrospective and prospective potential
-
Large number of imaging features defined & successfully implemented
-
Robust feature extraction pipeline implemented in 3D-Slicer (Python / Matlab)
-
Radiomics signatures are prognostic across cancer types
-
Radiomics data is strongly association with driving biological processes
-
Ongoing: “Delta radiomics” change of image features
-
Ongoing: Preclinical models with tumor models having inducible KO
-
Ongoing: Radiomics in clinical trial data
14
Take home message
The field of Forensic Bioinformatics (Keith Baggerly, MD Anderson)
Investigating the reproducibility and methodology of scientific studies in
retrospect. They request the data from the investigators, they assess the used
statistics, methods, results, and conclusions.
They find a large number of studies that are wrong or even fraud
Duke Scandal (Anil Potti)
Accused of falsifying data regarding the use of microarray genetic analysis for
personalized cancer treatment. Publications in various prestigious scientific
journals were retracted (including PNAS, Lancet Oncology, Nature Medicine,
JAMA, JCO, NEJM).
Forensic Radiology
Forensic Radiology
15
www.cibl-harvard.org
•
Emmanuel Rios-Velazques, PhD
•
Stephen Yip, PhD
•
Elizabeth Huynh, PhD
•
Patrick Grossmann, MSc
•
Thibaud Coroller, MSc
•
Chintan Parmar, MSc
•
Ying Hou, MD
•
Matthew Wagar, MSc
•
Vivek Narayan, BSc
•
Brian Alexander
•
John Quackenbush
•
Tina Kapur
•
Gisele Cruz
•
Raymound Mak
•
Nabgha Farhat
•
Fiona Fennessy
•
•
•
Mike Makrigiorgos •
Ross Berbecco
•
Philippe Lambin
•
Ralph Leijenaar
•
Sara Cavalho
•
Robbert Gillies
•
Yuhua Gu
•
Virendra Kumar
•
Olya Grove
•
Benjamin Haibe-Kains
•
Nehme Hachem
Ron Kikinis
Aedin Culhane
14/07/201
5
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46
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