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Coming Full Circle in Data Driven Discovery with JMP for Clinical and Translational Bioinformatics (2022-US-EPO-1166)

Jennfier Barb, Staff Scientist, National Institutes of Health
Gwenyth R. Wallen, Principal Investigator, NIH

 

JMP has been used by our interdisciplinary group at the NIH Clinical Center for the analysis of clinical research data to test and develop data-driven hypotheses supporting our bench to bedside to community and back translational model. We will present a workflow exemplar visualization of correlates between antibiotic use and patient-specific oral microbiomes. Starting with a spreadsheet of more than 2000 entries of antibiotic medication use in patients with a rare disease, and a separate spreadsheet of bacteria present in the oral microbiome from each patient, we created a visualization of the longitudinal antibiotic use through the course of the treatment program and correlated the use of the antibiotics with the oral microbiome diversity metrics. It is well known that the use of antibiotics can perturb the normal human microbiota yet its global effect on the oral microbiome remains unclear. We describe how the JMP Graph Builder tool was used to further explain whether antibiotics may have affected the oral microbiome in this rare disease patient cohort. The graphical nature of JMP has been used as a tool for data analytics within our group for years and has facilitated the publication of frequently cited peer-reviewed translational clinical research articles.   

 

 

Hello.

My  name  is  Jennifer  Barb, and  I'm  a  research  scientist

at  the  National  Institutes of  Health  Clinical  Center.

I'm  going  to  talk  to  you  today

about  how  I  use  JMP  to  manipulate research  clinical  medication  data

and  how  I  was  able  to  create a  publication  quality  figure

to  show  how the  patient  medications  were  used

through  the  course  of  a  treatment  protocol at  the  Clinical  Center.

Clinical  data,

especially  in  a  research  setting, can  be  extremely  noisy.

There  are  a  lot  of  staff  and  personnel who  are  involved  in  research  protocols,

and  the  collection  and  storage of  pertinent  research  data

is  not  always  streamlined.

I  will  talk  to  you  about  how  I  use the  JMP   Graph Builder  tool

to  visualize patient  medication  prescriptions

through  the  course of  a  six- month  treatment  protocol

and  how  we  were  able  to  visualize what  is  called  a   Shannon Diversity  Index

with  relation  to  the  antibiotic  use

that  were  prescribed in  the  patient  [inaudible 00:00:55]

in  the  clinical  research  setting.

I  will  go  through  how  I  created the  illustration  in  JMP

using  four  patients with  a  very  rare  disease

that  were  enrolled in  the  treatment  protocol.

As  part  of  the  treatment  regimen of  this  protocol,

the  four  patients  were  prescribed a  range  of  antibiotics,

totaling  up  to  21  different  types of  medications.

The  data  were  provided  to  me in  a  long  format,

including  a  start  and  stop  date of  medication  administration.

As  you  can  see  here,  I  zoomed into  the  first  figure  of  the  poster.

What  we're  looking  at  here  is  a  snapshot

of  what  some of  the  research  data  look  like.

In  the  long  format,

you  see  that  there  are  repetitive  rows of  the  patient  ID

and  there  are  repetitive  rows of  the  different  medications

that  the  patient  received during  the  treatment  protocol.

There's  a  lot  of  redundancy  here.

In  addition  to  that, we  have  a  start  of  medication  date

and  a  stop  of  medication  date that  each  person  received.

One  of  the  first  steps  I  had  to  take within  the  JMP  data  manipulation  tools

was  to  edit  the  medication  name so  that  it  did  not  have  so  many  words

in  the  medication  name

and  also  did  not  include the  dosage  information

so  that  we  could  use  this

as  one  of  the  axes  of  the  graph that  I'm  going  to  make.

In  addition  to  that, I  had  to  check  the  date  of  patient  consent

into  the  treatment  program

and  to  see  if  the  start  and  stop  date of  that  person's  medication  administration

fell  within  the  treatment  protocol.

From  that  point  then,  I  had  to  normalize each  person's  medication  start  and  stop

so  that  everybody  had  a  day  one and  it  would  all  corresponded

to  the  certain  point of  the  treatment  protocol.

All  of  this  information  will  be  used to  create  the  figure  that  I  will  show

at  the  end  of  this.

Once  I  was  able  to  edit the  medication  name

and  create  the  normalized medication  start  and  stop,

I  will  then  use  the   Graph Builder  tool.

I  also  wanted  to  talk  about one  other  aspect

of  this  particular  research  protocol,

and  that  is  the  fact that  we  wanted  to  look

at  the  oral  microbiome  of  the  patients in  the  treatment  program.

What  this  means  is  that

we  took  samples of  each  patient's  oral  tongue  brushings

and  then  converted  those into  specific  counts  of  bacteria

that  were  found  in  their  mouth.

What  we  ended  up  wanting  to  do  was to  look  at  how  the  antibiotic  treatment

through  the  treatment  protocol might  have  affected  the  oral  microbiome.

As  we  know,

antibiotics  can  drastically  change your  gut  microbiome

and  can  cause  increases  and  decreases

of  different  microbial  diversity in  the  gut.

But  one  question that  has  not  been  elucidated

is  whether  or  not  antibiotic  use would  also  affect  the  oral  microbiome.

What  I'm  showing  here  is  that

we  have  built  a  set  of  scripts within  the  JMP

where  we  install  that  on  the  toolbar.

We  have  a  specific  set  of  scripts that  would  calculate  the   Shannon Diversity

of  the  bacterial  counts  in  the  table

associated  with  the  medications  of  what I  just  showed  on  the  previous  slide.

Back  to  the  medication  table,

the  first  step  that  I  took  was  to  open  up the  JMP   Graph Builder  tool.

The  first  thing  that  I  did was  to  drag  and  drop

the  medication  start  and  stop  date into  the  X- axis  as  shown  here.

Then  I  would  go  to  the  bar  graph  tool

and  click  that  to  make the  data  into  a  bar  graph.

The  third  step  was  to  drag  and  drop

the  actual  antibiotic shortened  medicine  name

into  the  Y- axis.

And  then  finally,  in  order  to  create the  graph  so  that  I  could  visualize

the  longitudinal  duration of  medication  administration,

I  changed  the  bar  type  into  stock.

Finally, as  I  talked  to  you  earlier  about  the  way

in  which  we  were  able  to  code the  treatment  time  of  the  protocol

based  on  the  medication  start  and  stop,

we  also  were  able  to  stratify the  antibiotic  use

into  this  different  time  point of  the  treatment  protocol  as  here.

Now,  all  of  these,

if  you  are  familiar with  the  JMP   Graph Builder  tool,

is  great  ways  that there's  so  many  different  possibilities

on  how  you  can  manipulate  data to  get  a  particular  graph  that  you  want.

And  finally,  one  last  thing  we  did was  we  took  the  patient  ID

that  was  in  the  medication  table

and  colored  each  bar on  the  graph  by  patient.

The  final  figure  looks  like  this.

So  what  you  see  here is  all  of  the  different  antibiotics

that  were  prescribed in  the  treatment  protocol.

You  also  see  time  point  B,

which  is  the  time  point  between  baseline and  the  treatment  of  the  protocol,

and  time point  C, which  is  the  intervention  point

starting  at  time  point  C,  and  then  the  end of  the  treatment  protocol.

What  you  see  here  is  a  longitudinal  bar

indicating  the  amount  of  time a  person  was  on  a  given  antibiotic.

And  then  you  also  see each  of  these  different  bars

stratified  by  patient  color.

This  particular  figure  did  end  up  going into  the  publication,

and  it  was  a nother  way  to  look at  a  large  table  of  medications

downloaded  from  our  research  database into  a  graphical  form  to  visualize

all  of  the  different  medications

that  the  patient  received during  the  treatment.

Now,  finally,  you  might  want  to  ask, why  do  we  want  to  look  at  this?

One  thing  of  importance  for  us

was  to  actually  look at  the  oral  microbial  diversity.

As  I  mentioned,

we  were  able  to  take  a  separate  table that  corresponded  to  the  patients

within  the  treatment  protocol

and  calculate  what  is  called a   Shannon Diversity  metric.

A  higher  diversity  indicates higher  oral  microbial  diversity,

and  a  lower  index  indicates lower  microbial  diversity.

From  within  JMP, we  were  able  to  superimpose

the  treatment  leg between  time  point  A  and  B

and  the  change  of  the  diversity  metric

from  time  point  the  start  of  the  treatment to  the  end  of  the  treatment.

Also,  we're  able  to  look at  within  one  patient

how  the  different  antibiotics correspondent  to  this.

Then  the  second  leg  of  the  protocol, we  were  able  to  see  a  slight  rebound

of  the  diversity  index

in  correlation with  the  number  of  antibiotics

that  were  used  in  that  treatment  leg.

In  conclusion,

we  were  able  to  visualize patient- prescribed  antibiotics

through  the  course of  a  treatment  protocol

using  the  JMP   Graph Builder  tool.

We  took  a  table  of  1,289  rows of  medication  employed  in  the  protocol

and  created a  simplified  graph  of  visualization.

We  also  were  able  to  calculate a  Shannon  Diversity  Index

on  bacteria  data  associated with  each  person's  oral  samples.

We  superimpose  these  two  graphs, and  it  allowed  us  to  draw  conclusions

on  how  the  antibiotics prescribed  to  each  patient

might  have  affected  the  oral  microbiome of  individuals  in  the  treatment  protocol.

Finally,  our  group  has  used  the graphical  nature  of  JMP  for  many  years

in  a  way  to  translate complex  medical  research  data

into  data- driven  discovery and  investigation.

The  use  of  JMP  has  facilitated many  publications

and  highly  cited   research  journals for  our  group.

Thank  you  for  your  time  today.