1
2
3
4
5
6
7
8
9
10
11
12
13
14
15
16
17
18
19
20
21
22
23
24
25
26
27
28
29
30
31
32
33
34
35
36
37
38
39
40
41
42
43
44
45
46
47
48
49
50
51
52
53
54
55
56
57
58
59
60
61
62
63
64
65
66
67
68
69
70
71
72
73
74
75
76
77
78
79
80
81
82
83
84
85
86
87
88
89
90
91
92
93
94
95
96
97
98
99
100
101
102
103
104
105
106
107
108
109
110
111
112
113
114
115
116
117
118
119
120
121
122
123
124
125
126
127
128
129
130
131
132
133
134
135
136
137
138
139
140
141
142
143
144
145
146
147
148
149
150
151
152
153
154
155
156
157
158
159
160
161
162
163
164
165
166
|
id,name,dependent on
1,Kick-off meeting,
2,Definition of project plan,
3,Definition of roles and responsibilities,
4,Agreement on Data sharing modalities,
5,,
6,Aim 1 - Screen drugs against merlin-deficient VS and M cells,
7,Final list of compounds ready,
8,Assemble 20 to 40 drugs panel,
9,Drugs in hands,8
10,QC check on purchased drugs,9
11,MTA negotiation with companies to secure drug supply,
12,"Assemble, test growth rates and choose hum Upfront meningioma lines for M screening set ",
13,Assemble pairs of lines for VS screening set (total 8 lines) Upfront,
14,Optimize assay conditions,
15,Primary Screening of 20 to 40 drugs against both M and VS,"14,11,9"
16,Analysis of data from primary screening,15
17,Upload of primary screening data into Synapse and report,16
18,Secondary screening (independent Human M and VS lines) of top drugs,17
19,Analysis of secondary screening data from secondary screening and interpretation,18
20,Upload of data into Synapse and reporting - Identification report of active single agents,19
21,Primary screening of drug combination,"17,58"
22,Upload of primary screening of combination data into report Synapse and reporting,21
23,Secondary screening of drug combination,"57,21"
24,Upload of secondary screening data into Synapse and report - reporting,23
25,Selection of drug(s)/Combination(s) for invivo screening,23
26,Analysis of Human vs Mouse cell lines and selection of winner cell line for NCATS screen,"18,58,60,62"
27,Selection of 'winner' cell line,"26,64"
28,NCATS screening ,27
29,NCATS hit evaluation,28
30,Upload of data into Synapse and reporting,29
31,NCATS hits in primary (or secondary?) screening panels (?),30
32,Upload of data into Synapse and reporting,31
33,,
34,,
35,Aim 2 - Collect and Integrate molecular System data to define targets and improve models,
36,Exome/RNA analysis of human NF2-associated tumor at Novartis,"13,12"
37,First deposition of data into the Cancer Cell Line Encyclopedia,36
38,Report on Novartis's activities at project's meetings,36
39,Report on Novartis's activities at project's meetings,36
40,Report on Novartis's activities at project's meetings,36
41,Report on Novartis's activities at project's meetings,36
42,Report on Novartis's activities at project's meetings,36
43,,
44,Availability of data from DoD program at Gusella Lab on Exome scanning and RNAseq of Schwannomas and Meningiomas and upload on Synapse,
45,Upload of consortium members pre-existing data into Synapse,
46,Upload of publicly available data into the Synapse,"44, 45"
47,Transcriptome profile of untreated cell lines (baseline analysis),"12,13"
48,Upload Cell lines baseline characterization only,"13, 47"
49,Transcriptome profile of screening lines control vs treated/responders,17
50,Upload Control vs treated/responsers,49
51,Transcriptome profile of screening lines control vs treated/responders of drug combination,"49, 24"
52,Upload Control vs combination's responders,51
53,Report on transcriptome profiling,52
54,Jumping Library analysis of structural genomic changes in screening set lines,"12,13"
55,Report on Jumping Library analysis,54
56,TC call to decide first 6 cell lines to analyse,
57,Kinome analysis of cell lines for baseline characterization ,"56,12,13"
58,Upload of data into Synapse and reporting,57
59,Kinome analysis of single agent drug responding cell lines,17
60,Upload of data of single agent drug responding cell lines into Synapse,59
61,Kinome analysis of combination of drugs responding cell lines,24
62,Upload of data of combination of drugs responding cell lines into Synapse,61
63,Report of both single agent and combination responders cell lines,"59, 62"
64,Analysis of integrated system data,"44,37,46,51"
65,Report on analysis of integrated system data - Generate report a list of proposed new targets,"64,68,70"
66,"Target (genes, pathways) validation by shRNA",58
67,Report on ongoing activities,66
68,Final Report - ID of new targets for NF2,66
69,Screening of drugs against validated targets,68
70,Upload of data into Synapse and reporting,69
71,Develop CRISP/Cas modified NF2 mutant AC and SC lines,58
72,Upload of data into Synapse and reporting,71
73,Develop CRISPR/Cas modified lines bearing cooperating mutations,72
74,Upload of data into Synapse and reporting,73
75,Test CRISPR-Cas lines with active drug(s)/combination(s),22
76,Upload of data into Synapse and reporting,75
77,RNAseq of genetically mod lines,"65, 72"
78,Upload of data into Synapse and reporting,77
79,Creation of a new set of genetically-accurate screening panel for NF2,"75, 74"
80,Kinome analysis of invivo tumors,90
81,Upload of data into Synapse and reporting,80
82,RNAseq analysis of invivo tumors,90
83,Upload of data into Synapse and reporting,82
84,,
85,Aim 3 - Screen drugs invivo in genetically engineered mouse (VS) and xenograft (M) models,
86,Breeding of PeriostinCre; nf2flox/flox mice,
87,Report on first year activities,86
88,Evaluation of single agent responders for animal studies,"50, 60"
89,Test drug(s)/combination(s) in PeriostinCre; nf2flox/flox mice,"20,88,86"
90,First invivo drug testing (treatment),89
91,First invivo drug testing (statistics),90
92,Upload of data into Synapse and reporting,91
93,Evaluation of single agent responders for animal studies,"52, 62"
94,First invivo combination drug testing (treatment),93
95,First invivo combination drug testing (statistics),94
96,Upload of data into Synapse and reporting,95
97,Last invivo drug testing slot (treatment),
98,Last invivo drug testing (statistics),"89, 97"
99,Upload of data into Synapse and reporting,98
100,Colony breeding and stereotactic transplantation studies,
101,Report on first year activities,100
102,Evaluation of single agent responsers for animal studies,88
103,Test drug(s)/combination(s) in BenMen1 xenograft model,"100, 20, 10"
104,First invivo drug testing,103
105,Upload of data into Synapse and reporting,104
106,Evaluation of single agent responders for animal studies,93
107,First invivo drug testing,106
108,Upload of data into Synapse and reporting,107
109,Last invivo drug testing slot,103
110,Upload of data into Synapse and reporting,109
111,Prioritize drug(s) for NF2 clinical trials,"80, 82"
112,Supply human tumors,
113,Report on first year activities,112
114,Report on second year activities,113
115,Final report,112
116,Supply human tumors to Novartis for transcriptome and exome analysis and generation of transplantable human,
117,Analysis of human tumors from patients,
118,Report on first year activities,116
119,Report on second year activities,118
120,Neuropathological assessment of mouse model tumors,89
121,Upload of data into Synapse and Final Reporting,120
122,Generation of transplantable human xenograft,116
123,Model available to the community (???),122
124,,
125,Aim 4 - Identify at least 1 drug to move forward for a clinical trial,
126,Evaluation and Design of potential clinical trial(s),111
127,Clinical trial start,126
128,,
129,"Aim 5 - Data Sharing, Dissemination plan and management",
130,Setting up of Synapse platform (website,
131,Training of researchers for data input,130
132,"Data deposition, integration and sharing",131
133,Report on 1y activities,
134,Report on 2y activities,133
135,Final report,132
136,,
137,Project Group calls (bi-weekly),
138,Group call: decision on drug panel,
139,Group call: decision on first cell lines to investigate for kinome and transcriptome profile,
140,Group call: pre-existing data on drugs or cell lines to be uploaded in Synapse,
141,,
142,,
143,,
144,Project Management,
145,Synodos Meeting (kick-off),
146,General management,145
147,Synodos Meeting(NF conference),146
148,Synodos Meeting (Ext Review committee),146
149,First Year report,148
150,Synodos Meeting(NF conference),146
151,Synodos Meeting (Ext Review committee),146
152,Second Year report,151
153,Synodos Meeting(NF conference),146
154,Synodos Meeting (Ext Review committee),146
155,Final report,"154,146"
156,,
157,,
158,,
159,,
160,,
161,,
162,,
163,,
164,,
165,,
|