Ge#ng  the  Measure  of  Scien3fic  Papers

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Prof  Stephen  Curry12  February  2013

SOLE 2013

The lecture on primary literature interpretation was completely useless especially so close before exams; it seemed completely irrelevant to us and was not at all interesting, it appeared to be purely a method of self-gratification for Curry, to "show off" his successes in the field.

Warning:

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What  is  this  lecture  for?

• The  scien3fic  literature  is…

• …unavoidable,  daun3ng,  hard  to  read  (some3mes)

• What  do  you  need  to  know?

• How  it  is  produced

• How  to  read  it  (a  few  3ps)

• Papers  aren't  solely  wriJen  to  be  read…

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Star3ng  point:  What  is  a  scien3fic  paper  for?

• To  report  the  new  results  to  the  scien3fic  community

• formal  version  of  record

• To  establish  'priority'

• To  avoid  perishing…

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Where  did  journals  come  from?• 17th  Century  innova3on  -­‐  replaced  leJers

• Now  published  by  learned  socie3es  and  private  companies  (e.g.  Elsevier,  Springer,  Wiley,  NPG)

• There  are  1,000's  of  them

See  h0p://en.wikipedia.org/wiki/Scien=fic_journal5  January  16656  March  1665

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How  are  papers  wriJen?

• Different  types:• Primary  research  ar3cles  —  submiJed  when  you're  ready• Review  ar3cles  —  oYen  requested;  synthesis  of  the  literature

• When:• When  you  have  enough  informa3on?    • An  interes'ng  result  supported  by  addi3onal  experiments:  

e.g.  structure  and  func3on• What  about  nega3ve  results?

• How:• Who  is  the  audience  -­‐  small  community  of  peers;  who  else?  • Style  of  wri3ng:  1st  or  3rd  person?• Figures  —  always  tricky  to  get  right

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Figures  are  hard  to  make  and  read

Zunszain  et  al.  (2010)  J  Mol  Biol  395,  375–389  7

Submission  to  the  journal• Choice  of  journal?• Review  process:  editors  and  peer-­‐reviewers• Peer  reviewers

• unpaid,  usually  anonymous;  • author  can  ask  for  some  people  to  be  barred  from  reviewing• a  quality  check  (but  not  foolproof)

• Outcomes  of  the  review:  • reject,  minor  revision,  major  revision,  accept

Re:  JVI03151-­‐12  Structures  of  the  Compact  Helical  Core  Domains  of  Feline  Calicivirus  and  Murine  Norovirus  VPg  proteins

Dear  Stephen,Thank  you  for  submiWng  your  manuscript  to  Journal  of  Virology.  Below  you  will  find  the  comments  of  two  reviewers  who,  as  you  will  see,  liked  the  work  very  much  but  had  comments  about  the  func=onal  data  and  their  interpreta=on.  Revisions  are  requested…8

Costs  of  Publica3on

• Author  pays  —  from  a  grant(and  is  not  remunerated  for  wri3ng)

• Page  charges,  colour  figures  e.g.  J.  Virol.  -­‐  pages  $67-­‐$125  each;  colour  figs  $375

• Open  access:  addi3onal  charges  ($0-­‐$5000)  -­‐  see  later

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The  published  paper:  who  did  what?

• Significance  of  author  posi3on  in  list  (first  and  last  author)• Signposts  for  further  reading...

hJp://www.plosone.org/ar3cle/info%3Adoi%2F10.1371%2Fjournal.pone.003872310

The  published  paper:  read  the  abstract  first  (closely)

hJp://www.plosone.org/ar3cle/info%3Adoi%2F10.1371%2Fjournal.pone.0038723

AbstractMurine  noroviruses  have  emerged  as  a  valuable  tool  for  inves3ga3ng  the  molecular  basis  of  infec3on  and  pathogenesis  of  the  closely  related  human  noroviruses,  which  are  the  major  cause  of  non-­‐bacterial  gastroenteri3s.  The  replica3on  of  noroviruses  relies  on  the  proteoly3c  processing  of  a  large  polyprotein  precursor  into  six  non-­‐structural  proteins  (NS1–2,  NS3,  NS4,  NS5,  NS6pro,  NS7pol)  by  the  virally-­‐encoded  NS6  protease.  We  report  here  the  crystal  structure  of  MNV  NS6pro,  which  has  been  determined  to  a  resolu3on  of  1.6  Å.  Adven33ously,  the  crystal  contacts  are  mediated  in  part  by  the  binding  of  the  C-­‐terminus  of  NS6pro  within  the  pep3de-­‐binding  cleY  of  a  neighbouring  molecule.  This  inser3on  occurs  for  both  molecules  in  the  asymmetric  unit  of  the  crystal  in  a  manner  that  is  consistent  with  physiologically-­‐relevant  binding,  thereby  providing  two  independent  views  of  a  protease-­‐pep'de  complex.  Since  the  NS6pro  C-­‐terminus  is  formed  in  vivo  by  NS6pro  processing,  these  crystal  contacts  replicate  the  protease-­‐product  complex  that  is  formed  immediately  following  cleavage  of  the  pep'de  bond  at  the  NS6-­‐NS7  junc'on.  The  observed  mode  of  binding  of  the  C-­‐terminal  product  pep3de  yields  new  insights  into  the  structural  basis  of  NS6pro  specificity.

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Read  the  "News  &  Views"  (or  equivalent)

hJp://www.nature.com/nature/current_issue.html12

The  published  paper:  read  as  it  suits  you

Introduc'on• Why  is  this  problem  important?  • What  other  work  has  been  done  on  this  problem?

Results• What  experiments  did  we  do?• What  did  we  find?

Discussion• Why  what  we  found  is  interes3ng/significant

Materials  and  Methods• Enough  informa3on  for  others  to  repeat  the  study  (maybe)

Supplementary  Informa'on• Addi3onal  material  that  wasn't  interes3ng  enough  to  put  in  

the  body  of  the  paper  (internet  infla3on…)13

Just  because  it's  published  doesn't  mean  it's  an  easy  read

NLK  Is  a  Novel  Therapeu'c  Target  for  PTEN  Deficient  Tumour  CellsPTEN  (Phosphatase  and  tensin  homolog)  is  a  tumour  suppressor  gene  commonly  defec=ve  in  human  cancer,  and  is  thus  a  poten=ally  important  therapeu=c  target.  Targe=ng  tumour  suppressor  loss-­‐of-­‐func=on  is  possible  by  exploi=ng  the  gene=c  concept  of  synthe=c  lethality  (SL).  By  combining  the  use  of  isogenic  models  of  PTEN  deficiency  with  high-­‐throughput  RNA  interference  (RNAi)  screening,  we  have  iden=fied  Nemo-­‐Like  Kinase  (NLK)  inhibi=on  as  being  synthe=cally  lethal  with  PTEN  deficiency.  This  synthe=c  lethality  is  likely  mediated  by  the  transcrip=on  factor  FOXO1  (Forkhead  box  O1),  an  NLK  substrate,  as  the  selec=vity  of  NLK  gene  silencing  for  PTEN  deficient  cells  can  be  reversed  by  FOXO1  knockdown.  In  addi=on,  we  provide  evidence  that  PTEN  defec=ve  cells  targeted  by  NLK  gene  deple=on  undergo  senescence,  sugges=ng  that  NLK  func=on  is  cri=cal  for  the  con=nued  prolifera=on  of  PTEN  deficient  cells.  Taken  together,  these  data  provide  new  insight  into  the  poten=al  of  targe=ng  of  NLK  to  treat  a  range  of  tumourigenic  condi=ons  characterised  by  PTEN  deficiency.

PLoS  ONE  7(10):  e47249

To  be  fair,  it  is  hard  to  write  clearly  about  complex  ideas…14

The  published  paper:  how  good  is  it?• Published  but  is  it  true?

• Try  not  to  be  in3midated  —  your  are  allowed  to  cri3cise• Reviewers/authors  may  have  missed  something  • Mistakes  should  be  reported  

hJp://www.plosone.org/ar3cle/info%3Adoi%2F10.1371%2Fjournal.pone.003872315

Fraud:  some  'mistakes'  are  deliberate

See  also  hJp://www.science-­‐fraud.org

Why?

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Science  339,  386–389  (2013)

 Fraud:  how  common  is  it?

Ferric  Fang

Arturo  Casadevall

• A  small  minority

• On  the  increase?

See  also:  h0p://retrac=onwatch.wordpress.com17

What  else  is  a  paper  for?

To  advance  your  career  -­‐  'publish  or  perish'• Promo3on  

• Lecturer,  Senior  Lecturer,  Reader,  Professor• Grant  applica3ons  

• ~20%  success  rate  in  the  UK• Research  Excellence  Framework  (REF  2014)

• Assessment  of  research  in  UK  universi3es• Dept  submits  4  papers  for  every  member  of  staff  • A  key  determinant  of  future  income  from  govt  

The  hierarchy  of  journals  —  where  to  publish?•  The  impact  factor

See  also:  Lawrence,  P.  The  Heart  of  Research  is  Sick.  Lab  Times  24–31  (2011).18

Impact  factors:  a  measure  of  journals,  not  papers

Number  of  cita=ons  to  papers  in  past  2  yrs

Total  number  of  papers  published  in  past  2  yrs

For  each  journal,  impact  factor  =

Mean  value  of  IF  is  dominated  by  small  number  of  very  highly  cited  papers.  

Typically  only  15%  of  papers  have  more  cita=ons  than  average.  

IF  is  a  poor  measure  of  average/likely  performance

h0p://occamstypewriter.org/scurry/2012/08/13/sick-­‐of-­‐impact-­‐factors/From  Wikipedia19

Inside  the  College  database  of  staff  publica3ons

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Open  Access

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Where  are  scientific  journals  going?

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The  Web  changes  everything:  

Expectations  of  information  accessibility

Faster  publication  &  exchange

Scalability:  text  and  data  mining

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Policy  developments  in  the  UK  -­‐  2012

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Rt  Hon  David  WilleWs  MP:

The  "funding  model  is  surely  going  to  have  to  change  even  beyond  the  welcome  transi3on  to  open  access…  that’s  already  underway.  To  try  to  preserve  the  old  model  is  the  wrong  baWle  to  fight."

Dame  Janet  Finch:

“The  principle  that  the  results  of  research  that  has  been  publicly  funded  should  be  freely  accessible  in  the  public  domain  is  a  compelling  one,  and  fundamentally  unanswerable.”

UK  policy  from  April  2013

• All  publicly-­‐funded  research  must  be  open  access• Gold  OA  -­‐  immediately  available  in  OA  journal  

(costs  $0-­‐$5000)• Green  OA  -­‐  author's  version  of  manuscript  made  available  

aYer  6  months  ($0)

Big  debate...  (needs  another  lecture)• For  now,  UK  will  pay  OA  fees  and  journal  subscrip3ons…• UK:  only  6%  of  world's  research• For  policy  to  succeed,  need  the  whole  world  to  go  for  OA• But  nobody  knows  how…

h0p://www.economist.com/node/21559317h0p://occamstypewriter.org/scurry/2012/09/05/key-­‐ques=ons-­‐for-­‐open-­‐access-­‐policy-­‐in-­‐the-­‐uk/

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Just  publish?

Interes3ng  3mes...

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Ques3ons?

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