The Scientific Literature (UG lecture, Feb 2013)
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The Scientific Literature (UG lecture, Feb 2013)

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Now with an audio recording of my lecture (kindly provided by Emma Sherling). The sound quality is OK - there are a few noises at the start but then it settles down. The last minute or two of the talk ...

Now with an audio recording of my lecture (kindly provided by Emma Sherling). The sound quality is OK - there are a few noises at the start but then it settles down. The last minute or two of the talk were cut-off, unfortunately.

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The Scientific Literature (UG lecture, Feb 2013) The Scientific Literature (UG lecture, Feb 2013) Presentation Transcript

  • Ge#ng  the  Measure   of  Scien3fic  Papers Prof  Stephen  Curry 12  February  20131
  • SOLE 2013 The lecture on primary literature interpretation was completely useless especially so close before exams; it Warning: 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.2
  • 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  arent  solely  wriJen  to  be  read…3
  • 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…4
  • 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  1,000s  of  them 6  March  16655 5  January  1665 See  h0p://en.wikipedia.org/wiki/Scien=fic_journal
  • How  are  papers  wriJen? • Different  types: • Primary  research  ar3cles  —  submiJed  when  youre  ready • Review  ar3cles  —  oYen  requested;  synthesis  of  the  literature • When: • When  you  have  enough  informa3on?     • An  interesng  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  right6
  • Figures  are  hard  to   make  and  read Zunszain  et  al.  (2010)  7 J  Mol  Biol  395,  375–389  
  • 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.  8 Revisions  are  requested…
  • 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  later9
  • The  published  paper:  who  did  what? • Significance  of  author  posi3on  in  list  (first  and  last  author) • Signposts  for  further  reading...10 hJp://www.plosone.org/ar3cle/info%3Adoi%2F10.1371%2Fjournal.pone.0038723
  • The  published  paper:  read  the  abstract  first  (closely) Abstract Murine  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-­‐pepde  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  pepde  bond  at  the  NS6-­‐NS7  juncon.  The   observed  mode  of  binding  of  the  C-­‐terminal  product  pep3de  yields  new   insights  into  the  structural  basis  of  NS6pro  specificity.11 hJp://www.plosone.org/ar3cle/info%3Adoi%2F10.1371%2Fjournal.pone.0038723
  • Read  the  "News  &  Views"  (or  equivalent)12 hJp://www.nature.com/nature/current_issue.html
  • The  published  paper:  read  as  it  suits  you Introducon • 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  Informaon • Addi3onal  material  that  wasnt  interes3ng  enough  to  put  in  13 the  body  of  the  paper  (internet  infla3on…)
  • Just  because  its  published  doesnt  mean  its  an  easy  read NLK  Is  a  Novel  Therapeuc  Target   for  PTEN  Deficient  Tumour  Cells PTEN  (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):  e4724914 To  be  fair,  it  is  hard  to  write  clearly  about  complex  ideas…
  • 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  15 hJp://www.plosone.org/ar3cle/info%3Adoi%2F10.1371%2Fjournal.pone.0038723
  • Fraud:  some  mistakes  are  deliberate Why?16 See  also  hJp://www.science-­‐fraud.org
  •  Fraud:  how  common  is  it? Science  339,  386–389  (2013) Ferric  Fang • A  small  minority • On  the  increase? Arturo  Casadevall17 See  also:  h0p://retrac=onwatch.wordpress.com
  • 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  factor18 See  also:  Lawrence,  P.  The  Heart  of  Research  is  Sick.  Lab  Times  24–31  (2011).
  • Impact  factors:  a  measure  of  journals,  not  papers For  each  journal,  impact  factor  = Number  of  cita=ons  to  papers  in  past  2  yrs Total  number  of  papers  published  in  past  2  yrs 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 From  Wikipedia19 h0p://occamstypewriter.org/scurry/2012/08/13/sick-­‐of-­‐impact-­‐factors/
  • Inside  the  College  database  of  staff  publica3ons20
  • 21
  • Open  Access22
  • Where  are  scientific  journals  going? The  Web  changes  everything:   Expectations  of  information  accessibility Faster  publication  &  exchange Scalability:  text  and  data  mining 237
  • Policy  developments  in  the  UK  -­‐  2012 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.” 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."24
  • 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  -­‐  authors  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  worlds  research • For  policy  to  succeed,  need  the  whole  world  to  go  for  OA • But  nobody  knows  how… h0p://www.economist.com/node/21559317 h0p://occamstypewriter.org/scurry/2012/09/05/key-­‐ques=ons-­‐for-­‐open-­‐access-­‐policy-­‐in-­‐the-­‐uk/25
  • Just  publish? Interes3ng  3mes...26
  • Ques3ons?27