How do biologists infer correct ORF of a DNA sequence?
TransDecoder is a commonly used program for extracting likely coding regions from transcriptome assemblies, which does the following to make a call:


  TransDecoder identifies likely coding sequences based on the following
  criteria:
  
  
  a minimum length open reading frame (ORF) is found in a transcript
  sequence
  a log-likelihood score similar to what is computed by the GeneID
  software is > 0.
  the above coding score is greatest when the ORF is scored in the 1st
  reading frame as compared to scores in the other 5 reading frames.
  if a candidate ORF is found fully encapsulated by the coordinates of
  another candidate ORF, the longer one is reported. However, a single
  transcript can report multiple ORFs (allowing for operons, chimeras,
  etc).
  optional the putative peptide has a match to a Pfam domain above the
  noise cutoff score.
  


So in essence, look for the longest ORF, and then use some secondary metric (hidden Markov model, position weight array, database query, etc) to refine your prediction.