Automated system for the comparison of individual genome, transcriptome, proteome, epigenome, and metabolome data with data from bonemarrow donor registers and blood banks, umbilical cord blood banks and tissue banks
The invention relates to a system for the automatic, rapid and dynamic allocation of biological cells for transplantation, therapy, or research purposes between collection centers or banks (storage sites) and hospitals, transplant centers or research facilities, and for monitoring and supporting the processes from request transmission up to delivery of a cell preparation suitable for allogeneic transplantation, via the use of allocated preparations up to tracking the results in the patient and providing these data for statistical and other purposes, as well as assigning molecular-diagnostic results of individuals with the aim of verifying options—even in advance—of transplantations among the inventory of registers or banks. Using said system, it is possible for the first time—even in advance and online and with automatic retries—to propose complete solutions in the form of transplantations in specific and individual cases.
1. A system for allocating and selecting umbilical cord blood preparations, for transplantations, therapies and/or research purposes, wherein the system comprises data processing equipment including one or more processing units connected via a network of said one or more processing units via which data is exchanged,
wherein
said one or more processing units are configured to:
store experience data of umbilical cord blood preparations imputed into a computer via one or more input devices,
store inquiry data of a potential recipient or patient, said inquiry data comprising genome, transcriptome, proteome, epigenome and/or metabolome data,
store preset search criteria,
compare the experience data with the inquiry data, and automatically evaluate the search being effected, and/or
effect order processing and tracking on the basis of this evaluation, the umbilical cord blood preparation being ordered via the network, and wherein
the one or more processing units are configured to arrange and select potential umbilical cord blood preparations according to HLA match, patient weight, number of nucleated cells (TNC) and number of hematopoietic cells (CD34+) and, in addition, compare them with said genome, transcriptome, proteome, epigenome and/or metabolome data,
wherein the one or more processing units are configured to execute a patient search that comprises determining patient-compatible preparations in accordance with the following classification and/or exclusion criteria:
name and identification of clinic or transplantation center,
names of coordinator and attending physician, including contact data,
status of clinic with regard to international certifications (e.g. FACT),
average number of UCB transplantations in the inquiring clinic during the last three years,
name of patient, insurance number and other accounting information,
patient's medical history,
indication and therapy proposal of attending physician,
urgency according to defined classification,
HLA type of patient,
blood group of patient,
weight of patient,
ethnic group of patient,
sex of patient,
age of patient,
known allelic characteristics of patient and/or data of DNA typing, and/or
first treatment or re-treatment,
said classification and/or exclusion criteria being stored on one of said processing units, and
wherein the one or more processing units are configured to produce short list(s) of potential umbilical cord preparations, using the following settings:
ML
Prep
:=
{
6
:
HLA
Prep
and
HLA
Pat
match
in
6
out
of
6
typing
values
and
blood
group
compatibility
5
:
HLA
Prep
and
HLA
Pat
match
in
5
out
of
6
typing
values
and
blood
group
compatibility
4
:
HLA
Prep
and
HLA
Pat
match
in
4
out
of
6
typing
values
and
blood
group
compatibility
Preparation not included: other
wherein ML Prep =match level in accordance with HLA compatibility between preparation and patient,
CF
Prep
:=
{
3
×
10
7
:
ML
Prep
=
6
4
×
10
7
:
ML
Prep
=
5
5
×
10
7
:
ML
Prep
=
4
wherein CF Prep =cell factor defining required number of cells per kg of patient weight at corresponding match level,
CN
Prep
:=
TNC
Prep
CF
Prep
wherein CN Prep =classification number of a preparation allowing arrangement of preparations in accordance with TNC and match level, and wherein
the short list(s) of preparations to be considered for single transplants are produced using the following setting:
SL
Single
:=
{
p
∈
Prep
|
CN
p
BW
Pat
≥
1
kg
⋀
ML
Prep
≥
4
}
wherein SL Single =short list of preparations (p) to be considered for single transplants,
and wherein standard classifications of preparations in the short list(s) are made according to the following criteria:
Classification 1=initial ranking according to match level, followed by classification number, followed by CD34+
Classification
1
(
SL
)
:=
{
p
1
∈
SL
,
p
2
∈
SL
|
either
ML
p
1
>
ML
p
2
or
ML
p
1
=
ML
p
2
⋀
CN
p
1
>
CN
p
2
or
ML
p
1
=
ML
p
2
⋀
CN
p
1
=
CN
p
2
⋀
CD
34
p
1
≥
CD
34
p
2
and/or
Classification 2=initial ranking according to classification number, followed by match level, followed by CD34+
Classification
2
(
SL
)
:=
{
p
1
∈
SL
,
p
2
∈
SL
|
either
CN
p
1
>
CN
p
2
or
CN
p
1
=
CN
p
2
⋀
ML
p
1
>
ML
p
2
or
CN
p
1
=
CN
p
2
⋀
ML
p
1
=
ML
p
2
⋀
CD
34
p
1
+
≥
CD
34
p
2
+
wherein
Prep=umbilical cord blood preparation,
Pat=patient,
HLA Pat =HLA values of patient,
HLA Prep =HLA values of preparation,
TNC Prep =number of nucleated cells of preparation,
BW Pat =body weight of patient in kg,
CD34+ Prep =number of CD34+ cells of a preparation, and
p1, p2=preparation 1 selected, preparation 2 selected.
2. The system according to claim 1 ,
wherein the one or more processing units are configured to acquire data regarding umbilical cord blood preparations with a data set during data processing, which data set comprises following parameters:
name and identification of a UCB storage bank (UCB bank) of the preparation,
status of the UCB storage bank with regard to international certifications, preferably FACT,
process reliability of the UCB bank according to classification,
contact in the respective bank, including contact data,
identification number of preparation,
medical history of mother, child and family according to anamnesis form of the maternity clinic,
ethnic group of mother, father and/or child,
sex of child,
date of initial storage of preparation,
details of preparation processing,
blood group of preparation,
HLA type of preparation,
cell count (TNC) of preparation,
cell count (CD34+) of preparation,
viral status of preparation,
allelic characteristics of preparation, and/or
parameters of molecular diagnoses and analyses.
3. The system according to claim 1 ,
wherein
the genome data comprises sequenced chromosomes, genes and/or DNA of eukaryotes.
4. The system according to claim 1 ,
wherein
the transcriptome data comprises transcribed genes.
5. The system according to claim 1 ,
wherein
the proteome data comprises all proteins in a living organism, a tissue, a cell, or a cell compartment.
6. The system according to claim 1 ,
wherein
the metabolome data comprises flow rates or turnover rates, metabolite levels and enzyme activities of individual metabolic pathways and/or interactions between various metabolic pathways and/or compartmentalization of various metabolic pathways within a cell.
7. The system according to claim 1 ,
wherein
the epigenome data comprises all meiotically and mitotically heritable changes in gene expression that are not encoded in a DNA sequence.
8. The system according to claim 1 , wherein
the following classification and/or exclusion criteria are used:
preparations having a CD34+ cell count above 10% of the TNC count,
exclusion of preparations wherein less than 75% of the CD34+ cells survived and/or were activated in a CA (colony assay),
blood group identity,
ethnic identity,
gender,
age of preparation,
accreditation standard and/or
ranking of the UCB bank.
9. The system according to claim 1 ,
wherein said one or more processing units are configured to allocate double or multiple transplantations (multi-cord).
10. The system according to claim 9 ,
wherein said one or more processing units are configured to perform the selection of multi-cord preparations according to the following classification criteria:
ML
P
1
P
2
:=
{
6
:
HLA
Prep
1
and
HLA
Prep
2
match
in
6
out
of
6
typing
values
and
blood
group
compatibility
5
:
HLA
Prep
1
and
HLA
Prep
2
match
in
5
out
of
6
typing
values
and
blood
group
compatibility
4
:
HLA
Prep
1
and
HLA
Prep
2
match
in
4
out
of
6
typing
values
and
blood
group
compatibility
Preparation
not
included
:
other
wherein ML P1P2 =mutual compatibility of 2 preparations, and
BL
Multi
:=
{
p
∈
Prep
CN
p
BW
Pat
<
1
kg
⋀
ML
Prep
≥
4
}
wherein BL Multi =basic list to determine the selection list for multiple preparations, and wherein said one or more processing units are configured to prepare a short list of preparations to be included in multiple transplants according to the following formula:
SL
Multi
:=
{
p
1
∈
BL
Multi
,
p
2
∈
BL
Multi
|
ML
p
1
p
2
≥
4
⋀
CN
p
1
+
CN
p
2
BW
Pat
≥
1
}
,
SL Multi =short list of preparations to be included in multiple transplants,
wherein
p1=preparation 1 selected,
p2=preparation 2 selected, and
Multi=multiple transplants.
11. A non-transitory computer-readable storage medium storing instructions that when executed by a computer cause the computer to perform a method for allocating and selecting umbilical cord blood preparations, the method comprising:
accessing a storage medium of one or more processing units in which experience data of umbilical cord blood preparations from at least one collection center and/or storage site has been stored,
inputting inquiry data of a potential recipient or patient and storing the data on said storage medium, said inquiry data comprising genome, transcriptome, proteome, epigenome and/or metabolome data at at least one clinic, transplant center and/or research facility,
presetting search criteria on said storage medium,
performing a search wherein the experience data is compared with inquiry data and performing an automatic evaluation of the search, and
effecting order processing and tracking on the basis of this evaluation, and
ordering the umbilical cord blood preparation via a network, wherein potential umbilical cord blood preparations are
arranged and selected according to HLA match, patient weight, number of nucleated cells (TNC) and number of hematopoietic cells (CD34+), and
compared with genome, transcriptome, proteome, epigenome and/or metabolome data, wherein said allocation and selection takes place between said least one collection center and/or storage site and said at least one clinic, transplant center and/or research facility, which communicate with each other via wired and/or wireless connections on one or more processing units, medical systems, storage devices and/or special processors and are connected via a network of said multiple processing units, medical systems, storage devices and/or special processors via which data are exchanged wherein the instructions case the computer to execute a
patient search that comprises determining patient-compatible preparations in accordance with the following classification and/or exclusion criteria:
name and identification of clinic or transplantation center,
names of coordinator and attending physician, including contact data,
status of clinic with regard to international certifications (e.g. FACT),
average number of UCB transplantations in the inquiring clinic during the last three years,
name of patient, insurance number and other accounting information,
patient's medical history,
indication and therapy proposal of attending physician,
urgency according to defined classification,
HLA type of patient,
blood group of patient,
weight of patient,
ethnic group of patient,
sex of patient,
age of patient,
known allelic characteristics of patient and/or data of DNA typing, and/or
first treatment or re-treatment,
said classification and/or exclusion criteria being stored on the computer-readable storage medium, and
wherein the instructions case the computer is configured to produce short list(s) of potential umbilical cord preparations, using the following settings:
ML
Prep
:=
{
6
:
HLA
Prep
and
HLA
Pat
match
in
6
out
of
6
typing
values
and
blood
group
compatibility
5
:
HLA
Prep
and
HLA
Pat
match
in
5
out
of
6
typing
values
and
blood
group
compatibility
4
:
HLA
Prep
and
HLA
Pat
match
in
4
out
of
6
typing
values
and
blood
group
compatibility
Preparation
not
included
:
other
wherein ML Prep =match level in accordance with HLA compatibility between preparation and patient,
CF
Prep
:=
{
3
×
10
7
:
ML
Prep
=
6
4
×
10
7
:
ML
Prep
=
5
5
×
10
7
:
ML
Prep
=
4
wherein CF Prep =cell factor defining required number of cells per kg of patient weight at corresponding match level,
CN
Prep
:=
TNC
Prep
CF
Prep
wherein CN Prep =classification number of a preparation allowing arrangement of preparations in accordance with TNC and match level, and wherein
the short list(s) of preparations to be considered for single transplants are produced using the following setting:
SL
Single
:=
{
p
∈
Prep
|
CN
p
BW
Pat
≥
1
kg
⋀
ML
Prep
≥
4
}
wherein SL Single =short list of preparations (p) to be considered for single transplants,
and wherein standard classifications of preparations in the short list(s) are made according to the following criteria:
Classification 1=initial ranking according to match level, followed by classification number, followed by CD34+
Classification
1
(
SL
)
:=
{
p
1
∈
SL
,
p
2
∈
SL
|
either
ML
p
1
>
ML
p
2
or
ML
p
1
=
ML
p
2
⋀
CN
p
1
>
CN
p
2
or
ML
p
1
=
ML
p
2
⋀
CN
p
1
=
CN
p
2
⋀
CD
34
p
1
≥
CD
34
p
2
and/or
Classification 2=initial ranking according to classification number, followed by match level, followed by CD34+
Classification
2
(
SL
)
:=
{
p
1
∈
SL
,
p
2
∈
SL
|
either
CN
p
1
>
CN
p
2
or
CN
p
1
=
CN
p
2
⋀
ML
p
1
>
ML
p
2
or
CN
p
1
=
CN
p
2
⋀
ML
p
1
=
ML
p
2
⋀
CD
34
p
1
+
≥
CD
34
p
2
+
wherein
Prep=umbilical cord blood preparation,
Pat=patient,
HLA Pat =HLA values of patient,
HLA Prep =HLA values of preparation,
TNC Prep =number of nucleated cells of preparation,
BW Pat =body weight of patient in kg,
CD34+ Prep =number of CD34+ cells of a preparation, and
p1, p2=preparation 1 selected, preparation 2 selected.